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  • 1.
    Akhras, Michael S.
    et al.
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Pettersson, Erik
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Diamond, Lisa
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Unemo, Magnus
    Örebro University Hospital.
    Okamoto, Jennifer
    Dept Bioengn, Stanford Univ, Stanford CA, USA.; Howard Hughes Med Inst, Stanford Univ, Stanford CA, USA.
    Davis, Ronald W.
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA , USA.
    Pourmand, Nader
    Dept Biomol Engn, University of California, Santa Cruz CA, USA.
    The Sequencing Bead Array (SBA), a Next-Generation Digital Suspension Array2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 10, article id UNSP e76696Article in journal (Refereed)
    Abstract [en]

    Here we describe the novel Sequencing Bead Array (SBA), a complete assay for molecular diagnostics and typing applications. SBA is a digital suspension array using Next-Generation Sequencing (NGS), to replace conventional optical readout platforms. The technology allows for reducing the number of instruments required in a laboratory setting, where the same NGS instrument could be employed from whole-genome and targeted sequencing to SBA broad-range biomarker detection and genotyping. As proof-of-concept, a model assay was designed that could distinguish ten Human Papillomavirus (HPV) genotypes associated with cervical cancer progression. SBA was used to genotype 20 cervical tumor samples and, when compared with amplicon pyrosequencing, was able to detect two additional co-infections due to increased sensitivity. We also introduce in-house software Sphix, enabling easy accessibility and interpretation of results. The technology offers a multi-parallel, rapid, robust, and scalable system that is readily adaptable for a multitude of microarray diagnostic and typing applications, e. g. genetic signatures, single nucleotide polymorphisms (SNPs), structural variations, and immunoassays. SBA has the potential to dramatically change the way we perform probe-based applications, and allow for a smooth transition towards the technology offered by genomic sequencing.

  • 2.
    Alirol, Emilie
    et al.
    Global Antibiotics Research and Development Partnership (GARDP), Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
    Wi, Teodora E.
    World Health Organization (WHO), Geneva, Switzerland.
    Bala, Manju
    Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Bazzo, Maria Luiza
    Federal University of Santa Catarina, Florianópolis, Brazil.
    Chen, Xiang-Sheng
    National Center for STD Control, Chinese Academy of Medical Sciences, Nanjing, China; Peking Union Medical College Institute of Dermatology, Nanjing, China.
    Deal, Carolyn
    STD Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), Rockville MD, United States of America.
    Dillon, Jo-Anne R.
    University of Saskatchewan, Saskatoon SK, Canada.
    Kularatne, Ranmini
    Centre for HIV & Sexually Transmitted Infections, National Institute for Communicable Diseases, Johannesburg, South Africa.
    Heim, Jutta
    Global Antibiotics Research and Development Partnership (GARDP), Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
    Hooft van Huijsduijnen, Rob
    Global Antibiotics Research and Development Partnership (GARDP), Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
    Hook, Edward W.
    University of Alabama, Birmingham AL, United States of America.
    Lahra, Monica M.
    World Health Organization Collaborating Centre for Sexually Transmitted Diseases, South Eastern Area Laboratory Services, The Prince of Wales Hospital, Sydney, Australia.
    Lewis, David A.
    Western Sydney Sexual Health Centre, Parramatta NSW, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney Medical School-Westmead, University of Sydney, Westmead, Australia.
    Ndowa, Francis
    Skin & GU Medicine Clinic, Harare, Zimbabwe.
    Shafer, William M.
    Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta GA, United States of America; Laboratories of Bacterial Pathogenesis, VA Medical Center, Decatur GA, United States of America.
    Tayler, Liz
    World Health Organization (WHO), Geneva, Switzerland.
    Workowski, Kimberly
    Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta GA, United States of America.
    Unemo, Magnus
    World Health Organization Collaborating Centre for Gonorrhoea and other STIs, Örebro University Hospital, Örebro, Sweden.
    Balasegaram, Manica
    Global Antibiotics Research and Development Partnership (GARDP), Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
    Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicines2017In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, no 7, article id e1002366Article in journal (Refereed)
    Abstract [en]

    Emilie Alirol and colleagues discuss the development of new treatments for gonorrhea.

  • 3.
    Al-Maslamani, Muna
    et al.
    Hamad Medical Corporation, Doha, Qatar.
    Elmagboul, Emad Bashier Ibrahim
    Hamad Medical Corporation, Doha, Qatar; Infectious Diseases Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar.
    Puthiyottil, Aslam
    Hamad Medical Corporation, Doha, Qatar.
    Chemaitelly, Hiam
    Infectious Diseases Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar; World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar.
    Varghese, Manoj Kizhakkepeedikayil
    Hamad Medical Corporation, Doha, Qatar.
    Al Romaihi, Hamad Eid
    Ministry of Public Health, Doha, Qatar.
    Al-Thani, Mohamed H.
    Ministry of Public Health, Doha, Qatar.
    Al Khal, Abdullatif
    Hamad Medical Corporation, Doha, Qatar.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Örebro University, Örebro, Sweden; Institute for Global Health, University College London, London, United Kingdom.
    Abu-Raddad, Laith J.
    Infectious Diseases Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar; World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar; Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York City, New York, United States of America; Department of Public Health, College of Health Sciences, Member of QU Health, Qatar University, Doha, Qatar.
    First characterisation of antimicrobial susceptibility and resistance of Neisseria gonorrhoeae isolates in Qatar, 2017-20202022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 3, article id e0264737Article in journal (Refereed)
    Abstract [en]

    Limited data are available regarding antimicrobial resistance in Neisseria gonorrhoeae strains circulating in WHO Eastern Mediterranean Region (EMR). We investigated the antimicrobial susceptibility/resistance of N. gonorrhoeae isolates to five antimicrobials (ceftriaxone, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin) currently or previously used for gonorrhoea treatment in Qatar, 2017-2020. Minimum inhibitory concentrations (MICs; mg/L) of antimicrobials were determined using Etest on gonococcal isolates collected during January 1, 2017-August 30, 2020 at Hamad Medical Corporation, a national public healthcare provider. During 2017-2020, resistance in isolates from urogenital sites of 433 patients was 64.7% (95% CI: 59.5-69.6%; range: 43.9-78.7%) for ciprofloxacin, 50.7% (95% CI: 45.3-56.1%; range: 41.3-70.4%) for tetracycline, and 30.8% (95% CI: 26.3-35.6%; range: 26.7-35.8%) for benzylpenicillin. Percentage of isolates non-susceptible to azithromycin was 4.1% (95% CI: 2.0-7.4%; range: 2.7-4.8%) and all (100%) isolates were susceptible to ceftriaxone. Two (1.6%) isolates from 2019 and one (2.2%) isolate from 2020 had high-level resistance to azithromycin (MIC≥256 mg/L). Overall, 1.0% (4/418) of isolates had a ceftriaxone MIC of 0.25 mg/L, which is at the ceftriaxone susceptibility breakpoint (MIC≤0.25 mg/L). Treatment with ceftriaxone 250 mg plus azithromycin 1 g can continuously be recommended for gonorrhoea therapy in Qatar. Continued quality-assured gonococcal AMR surveillance is warranted in EMR.

  • 4.
    Aniskevich, Aliaksandra
    et al.
    Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus.
    Shimanskaya, Iryna
    Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus.
    Boiko, Iryna
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine; World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections (STIs), National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Golubovskaya, Tatyana
    Mogilev Regional Skin and Venereal Diseases Dispensary, Mogilev, Belarus.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections (STIs), National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology.
    Stanislavova, Iryna
    Mogilev Regional Skin and Venereal Diseases Dispensary, Mogilev, Belarus.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections (STIs), National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology.
    Adaskevich, Aliaksandr
    Mogilev Regional Skin and Venereal Diseases Dispensary, Mogilev, Belarus.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections (STIs), National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology.
    Antimicrobial resistance in Neisseria gonorrhoeae isolates and gonorrhoea treatment in the Republic of Belarus, Eastern Europe, 2009-20192021In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 21, no 1, article id 520Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Limited antimicrobial resistance (AMR) data for Neisseria gonorrhoeae are available in Eastern Europe. We investigated AMR in N. gonorrhoeae isolates in the Republic of Belarus from 2009 to 2019, antimicrobial treatment recommended nationally, and treatment given to patients with gonorrhoea.

    METHODS: N. gonorrhoeae isolates (n = 522) cultured in three regions of Belarus in 2009-2019 were examined. Determination of minimum inhibitory concentrations (MICs) of eight antimicrobials was performed using Etest. Resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing were applied where available. A Nitrocefin test identified β-lactamase production. Gonorrhoea treatment for 1652 patients was also analysed. Statistical significance was determined by the Z-test, Fisher's exact test, or Mann-Whitney U test with p-values of < 0.05 indicating significance.

    RESULTS: In total, 27.8% of the N. gonorrhoeae isolates were resistant to tetracycline, 24.7% to ciprofloxacin, 7.0% to benzylpenicillin, 2.7% to cefixime, and 0.8% to azithromycin. No isolates were resistant to ceftriaxone, spectinomycin, or gentamicin. However, 14 (2.7%) isolates had a ceftriaxone MIC of 0.125 mg/L, exactly at the resistance breakpoint (MIC > 0.125 mg/L). Only one (0.2%) isolate, from 2013, produced β-lactamase. From 2009 to 2019, the levels of resistance to ciprofloxacin and tetracycline were relatively high and stable. Resistance to cefixime was not identified before 2013 but peaked at 22.2% in 2017. Only sporadic isolates with resistance to azithromycin were found in 2009 (n = 1), 2012 (n = 1), and 2018-2019 (n = 2). Overall, 862 (52.2%) patients received first-line treatment according to national guidelines (ceftriaxone 1 g). However, 154 (9.3%) patients received a nationally recommended alternative treatment (cefixime 400 mg or ofloxacin 400 mg), and 636 (38.5%) were given non-recommended treatment.

    CONCLUSIONS: The gonococcal resistance to ciprofloxacin and tetracycline was high, however, the resistance to azithromycin was low and no resistance to ceftriaxone was identified. Ceftriaxone 1 g can continuously be recommended as empiric first-line gonorrhoea therapy in Belarus. Fluoroquinolones should not be prescribed for treatment if susceptibility has not been confirmed by testing. Timely updating and high compliance with national evidence-based gonorrhoea treatment guidelines based on quality-assured AMR data are imperative. The need for continued, improved and enhanced surveillance of gonococcal AMR in Belarus is evident.

  • 5.
    Ariel Gianecini, Ricardo
    et al.
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Poklepovich, Tomas
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. World Health Organization Collaborating Centre for Gonorrhoea and Other STIs.
    Cuenca, Noelia
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Tuduri, Ezequiel
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and Other STIs.
    Campos, Josefina
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Galarza, Patricia
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Genomic Epidemiology of Azithromycin-Nonsusceptible Neisseria gonorrhoeae, Argentina, 2005-20192021In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 27, no 9, p. 2369-2378Article in journal (Refereed)
    Abstract [en]

    Azithromycin-nonsusceptible Neisseria gonorrhoeae strains are an emerging global public health threat. During 2015-2018, the prevalence of azithromycin-nonsusceptible gonococcal infection increased significantly in Argentina. To investigate the genomic epidemiology and resistance mechanisms of these strains, we sequenced 96 nonsusceptible isolates collected in Argentina during 2005-2019. Phylogenomic analysis revealed 2 main clades, which were characterized by a limited geographic distribution, circulating during January 2015-November 2019. These clades included the internationally spreading multilocus sequence types (STs) 1580 and 9363. The ST1580 isolates, which had MICs of 2-4 mu g/mL, had mutations in the 23S rRNA. The ST9363 isolates, which had MICs of 2-4 or >256 mu g/mL, had mutations in the 23S rRNA, a mosaic mtr locus, or both. Identifying the geographic dissemination and characteristics of these predominant clones will guide public health policies to control the spread of azithromycin-nonsusceptible N. gonorrhoeae in Argentina.

  • 6. Aspholm, Marina
    et al.
    Kalia, Awdhesh
    Ruhl, Stefan
    Schedin, Staffan
    Arnqvist, Anna
    Lindén, Sara
    Sjöström, Rolf
    Gerhard, Markus
    Semino-Mora, Cristina
    Dubois, Andre
    Unemo, Magnus
    Örebro University, Department of Clinical Medicine.
    Danielsson, Dan
    Teneberg, Susann
    Lee, Woo-Kon
    Berg, Douglas E.
    Borén, Thomas
    Helicobacter pylori adhesion to carbohydrates2006In: Methods in Enzymology, ISSN 0076-6879, E-ISSN 1557-7988, Vol. 417, p. 293-339Article in journal (Refereed)
    Abstract [en]

    Adherence of bacterial pathogens to host tissues contributes to colonization and virulence and typically involves specific interactions between bacterial proteins called adhesins and cognate oligosaccharide (glycan) or protein motifs in the host that are used as receptors. A given pathogen may have multiple adhesins, each specific for a different set of receptors and, potentially, with different roles in infection and disease. This chapter provides strategies for identifying and analyzing host glycan receptors and the bacterial adhesins that exploit them as receptors, with particular reference to adherence of the gastric pathogen Helicobacter pylori.

  • 7.
    Attram, Naiki
    et al.
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
    Agbodzi, Bright
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
    Dela, Helena
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
    Behene, Eric
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
    Nyarko, Edward O.
    Department of Public Health, Military Hospital, Accra, Ghana.
    Kyei, Nicholas N. A.
    Department of Public Health, Military Hospital, Accra, Ghana.
    Larbi, John A.
    Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
    Lawson, Bernard W. L.
    Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
    Addo, Kennedy K.
    Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
    Newman, Mercy J.
    Department of Medical Microbiology, School of Biomedical and Allied Health Science, College of Health Sciences, University of Ghana, Accra, Ghana.
    Duplessis, Christopher A.
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana.
    Adams, Nehkonti
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Letizia, Andrew G.
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana.
    Antimicrobial resistance (AMR) and molecular characterization of Neisseria gonorrhoeae in Ghana, 2012-20152019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 10, article id e0223598Article in journal (Refereed)
    Abstract [en]

    Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is essential for tracking the emergence and spread of AMR strains in local, national and international populations. This is crucial for developing or refining treatment guidelines. N. gonorrhoeae multiantigen sequence typing (NG-MAST) is beneficial for describing the molecular epidemiology of gonococci at national and international levels. Elucidation of AMR determinants to β-lactam drugs, is a means of monitoring the development of resistance. In Ghana, little is known about the current gonococcal AMR prevalence and no characterization of gonococcal isolates has been previously performed. In this study, gonococcal isolates (n = 44) collected from five health facilities in Ghana from 2012 to 2015, were examined using AMR testing, NG-MAST and sequencing of penA. High rates of resistance were identified to tetracycline (100%), benzylpenicillin (90.9%), and ciprofloxacin (81.8%). One isolate had a high cefixime MIC (0.75 μg/ml). Twenty-eight NG-MAST sequence types (STs) were identified, seventeen of which were novel. The isolate with the high cefixime MIC contained a mosaic penA-34 allele and belonged to NG-MAST ST1407, an internationally spreading multidrug-resistant clone that has accounted for most cefixime resistance in many countries. In conclusion, AMR testing, NG-MAST, and sequencing of the AMR determinant penA, revealed high rates of resistance to tetracycline, benzylpenicillin, and ciprofloxacin; as well as a highly diverse population of N. gonorrhoeae in Ghana. It is imperative to continue with enhanced AMR surveillance and to understand the molecular epidemiology of gonococcal strains circulating in Ghana and other African countries.

  • 8.
    Ayala, Julio C.
    et al.
    Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA.
    Schmerer, Matthew W.
    STD Laboratory Reference and Research Branch, Division of STD Prevention, NCHHSTP, Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
    Kersh, Ellen N.
    STD Laboratory Reference and Research Branch, Division of STD Prevention, NCHHSTP, Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology.
    Shafer, William M.
    Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; Emory Antibiotic Resistance Center, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center, Decatur, Georgia, USA.
    Gonococcal Clinical Strains Bearing a Common gdhR Single Nucleotide Polymorphism That Results in Enhanced Expression of the Virulence Gene lctP Frequently Possess a mtrR Promoter Mutation That Decreases Antibiotic Susceptibility2022In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 13, no 2, article id e0027622Article in journal (Refereed)
    Abstract [en]

    GdhR is a transcriptional repressor of the virulence factor gene lctP, which encodes a unique l-lactate permease that has been linked to pathogenesis of Neisseria gonorrhoeae, and loss of gdhR can confer increased fitness of gonococci in a female mouse model of lower genital tract infection. In this work, we identified a single nucleotide polymorphism (SNP) in gdhR, which is often present in both recent and historical gonococcal clinical strains and results in a proline (P)-to-serine (S) change at amino acid position 6 (P6S) of GdhR. This mutation (gdhR6) was found to reduce GdhR transcriptional repression at lctP in gonococcal strains containing the mutant protein compared to wild-type GdhR. By using purified recombinant proteins and in vitro DNA-binding and cross-linking experiments, we found that gdhR6 impairs the DNA-binding activity of GdhR at lctP without an apparent effect on protein oligomerization. By analyzing a panel of U.S. (from 2017 to 2018) and Danish (1928 to 2013) clinical isolates, we observed a statistical association between gdhR6 and the previously described adenine deletion in the promoter of mtrR (mtrR-P A-del), encoding the repressor (MtrR) of the mtrCDE operon that encodes the MtrCDE multidrug efflux pump that can export antibiotics, host antimicrobials, and biocides. The frequent association of gdhR6 with the mtrR promoter mutation in these clinical isolates suggests that it has persisted in this genetic background to enhance lctP expression, thereby promoting virulence. IMPORTANCE We report the frequent appearance of a novel SNP in the gdhR gene (gdhR6) possessed by Neisseria gonorrhoeae. The resulting amino acid change in the GdhR protein resulted in enhanced expression of a virulence gene (lctP) that has been suggested to promote gonococcal survival during infection. The mutant GdhR protein expressed by gdhR6 had a reduced ability to bind to its target DNA sequence upstream of lctP. Interestingly, gdhR6 was found in clinical gonococcal strains isolated in the United States and Denmark at a high frequency and was frequently associated with a mutation in the promoter of the gene encoding a repressor (MtrR) of both the mtrCDE antimicrobial efflux pump operon and gdhR. Given this frequent association and the known impact of these regulatory mutations, we propose that virulence and antibiotic resistance properties are often phenotypically linked in contemporary gonococcal strains.

  • 9.
    Bala, Manju
    et al.
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Singh, Vikram
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Philipova, Ivva
    WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden; National Reference Laboratory for Mycology and Sexually Transmitted Infections (STIs), National Center of Infections and Parasitic Diseases, Sofia, Bulgaria.
    Bhargava, Aradhana
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Chandra Joshi, Naveen
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Unemo, Magnus
    Örebro University, School of Health Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Gentamicin in vitro activity and tentative gentamicin interpretation criteria for the CLSI and calibrated dichotomous sensitivity disc diffusion methods for Neisseria gonorrhoeae2016In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 7, p. 1856-1859Article in journal (Refereed)
    Abstract [en]

    Objectives: XDR Neisseria gonorrhoeae imposes the threat of untreatable gonorrhoea. Gentamicin is considered for future treatment; however, no interpretation criteria for the CLSI and calibrated dichotomous sensitivity (CDS) disc diffusion (DD) techniques are available for N. gonorrhoeae. We investigated the in vitro gentamicin activity by MIC and DD methods, proposed DD breakpoints and determined DD ranges for 10 international quality control (QC) strains.

    Methods: Gentamicin susceptibility of 333 N. gonorrhoeae isolates, including 323 clinical isolates and 10 QC strains, was determined. MIC determination (Etest) and DD methods (CLSI and CDS) were performed. The relationship between MIC, inhibition zone diameter and annular radius was determined by linear regression analysis and the correlation coefficient (r) was calculated.

    Results: Gentamicin MICs for the QC strains were within published ranges. Of the 323 clinical isolates, according to published breakpoints 75.9%, 23.5% and 0.6% were susceptible, intermediately susceptible and resistant, respectively. Based on error minimization with MICs of ≤4, 8-16 and ≥32 mg/L, breakpoints proposed are susceptible ≥16 mm, intermediately susceptible 13-15 mm and resistant ≤12 mm for the CLSI method and susceptible ≥6 mm, less susceptible 3-5 mm and resistant ≤2 mm for the CDS technique.

    Conclusions: Low resistance to gentamicin was identified and gentamicin might be a future treatment option for gonorrhoea. Tentative gentamicin zone breakpoints were defined for two DD methods and QC ranges for 10 international reference strains were established. Our findings suggest that in resource-poor settings where MIC testing is not a feasible option, the DD methods can be used to indicate gentamicin resistance.

  • 10.
    Banhart, S.
    et al.
    Fachgebiet‚ Sexuell übertragbare bakterielle Krankheitserreger‘, Abteilung für Infektionskrankheiten, Robert Koch-Institut, Berlin, Deutschland.
    Jansen, K.
    Fachgebiet‚ HIV/AIDS und andere sexuell oder durch Blut übertragbare Infektionen‘, Abteilung für Infektionsepidemiologie, Robert Koch-Institut, Berlin, Deutschland.
    Buder, S.
    Konsiliarlabor für Gonokokken, Vivantes Klinikum Neukölln, Berlin, Deutschland.
    Tamminga, T.
    Robert Koch Inst, Abt Infekt Krankheiten, Fachgebiet HIV AIDS & Andere Sexuell Oder Durch B, Berlin, Germany..
    Calvignac-Spencer, S.
    Projektgruppe‚ Epidemiologie hochpathogener Erreger‘, Robert Koch-Institut, Berlin, Deutschland.
    Pilz, T.
    Fachgebiet‚ Sexuell übertragbare bakterielle Krankheitserreger‘, Abteilung für Infektionskrankheiten, Robert Koch-Institut, Berlin, Deutschland.
    Martini, A.
    Fachgebiet‚ Sexuell übertragbare bakterielle Krankheitserreger‘, Abteilung für Infektionskrankheiten, Robert Koch-Institut, Berlin, Deutschland.
    Dudareva, S.
    Fachgebiet‚ HIV/AIDS und andere sexuell oder durch Blut übertragbare Infektionen‘, Abteilung für Infektionsepidemiologie, Robert Koch-Institut, Berlin, Deutschland; WHO Collaborating Centre for Gonorrhoea and Other STIs, Faculty of Medicine and Health, Örebro University, Örebro, Schweden.
    Nikisins, S.
    Fachgebiet‚ HIV/AIDS und andere sexuell oder durch Blut übertragbare Infektionen‘, Abteilung für Infektionsepidemiologie, Robert Koch-Institut, Berlin, Deutschland.
    Dehmel, K.
    Fachgebiet‚ HIV/AIDS und andere sexuell oder durch Blut übertragbare Infektionen‘, Abteilung für Infektionsepidemiologie, Robert Koch-Institut, Berlin, Deutschland.
    Zuelsdorf, G.
    Fachgebiet‚ HIV/AIDS und andere sexuell oder durch Blut übertragbare Infektionen‘, Abteilung für Infektionsepidemiologie, Robert Koch-Institut, Berlin, Deutschland.
    Guhl, E.
    Graeber, I
    Konsiliarlabor für Gonokokken, Vivantes Klinikum Neukölln, Berlin, Deutschland.
    Koh, P. K.
    Vivantes Klinikum Neukolln, Konsiliarlabor Gonokokken, Berlin, Germany..
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs.
    Bremer, V
    Fachgebiet‚ HIV/AIDS und andere sexuell oder durch Blut übertragbare Infektionen‘, Abteilung für Infektionsepidemiologie, Robert Koch-Institut, Berlin, Deutschland.
    Heuer, D.
    Fachgebiet‚ Sexuell übertragbare bakterielle Krankheitserreger‘, Abteilung für Infektionskrankheiten, Robert Koch-Institut, Berlin, Deutschland.
    Identification of a new Association between Genogroup G10557 (G7072) and Cefixime Resistance by means of molecular Typing of Neisseria gonorrhoeae Isolates in Germany (2014-2017)2021In: Der Hautarzt, ISSN 0017-8470, E-ISSN 1432-1173, Vol. 72, no Suppl. 1, p. S8-S9Article in journal (Other academic)
    Abstract [de]

    Hintergrund/Fragestellung: Die Behandlung von Neisseria gonorrhoeae-Infektionen ist aufgrund sich neu entwickelnder Antibiotikaresistenzen gefährdet. Folglich sind Surveillance-Programme zur Beschreibung der antimikrobiellen Resistenz (AMR) und molekularen Epidemiologie bei Gonokokken auf nationaler und internationaler Ebene dringend erfor-derlich. In Deutschland wurde hierfür im Jahr 2013 das Gonokokken-Resistenznetzwerk (GORENET) etabliert. Unser Ziel war es, die geneti-sche Diversität von N. gonorrhoeae-Isolaten in Deutschland von 2014 bis 2017 mittels NG-MAST (N. gonorrhoeae multi-antigen sequence typing) zu beschreiben.

    Methoden: N. gonorrhoeae-Isolate aus den Jahren 2014–2017 (n=1220; 106 aus 2014, 122 aus 2015, 511 aus 2016 und 481 aus 2017) wurden deutschlandweit eingesandt und mittels AMR-Testung und NG-MAST charakterisiert.

    Ergebnisse: 88,4% aller Isolate stammten von Männern, 11,2% von Frauen. Das mediane Alter lag bei 32 Jahren (Interquartalsabstand; IQA: 25–44 Jahre). Insgesamt wurden 432 verschiedene NG-MAST-Sequenztypen (STs) einschließlich 146 neuer STs detektiert. Daraus resultieren 17 verschiedene Genogruppen, welche 59,2% aller Isolate beinhalten. Genogruppen G1407 und G10557 (G7072) waren signifikant mit Cefixim-Resistenz assoziiert. Dabei sank der Anteil dieser Genogruppen von 2014–2017 von 14,2 auf 6,2% (G1407) bzw. von 6,6 auf 3,1% (G10557 (G7072)),wohingegen der Anteil mehrerer Cefixim-empfindlicher Genogruppen (G11461, von 0,0 auf 5,6%; G17420, von 0,0 auf 5,0%; und G5441, von 0,9 und 4,8%) im gleichen Zeitraum anstieg.

    Schlussfolgerungen: In dieser Arbeit beschreiben wir Neisseria gonorrhoeae in Deutschland als eine genetisch diverse und variable Population und identifizieren eine neue Assoziation zwischen Genogruppe G10557 (G7072) und Cefixim-Resistenz. Diese Ergebnisse unterstreichen die Bedeutung der AMR-Überwachung auf der detaillierten Ebene molekularer Typisierung. Darüber hinaus deuten unsere Daten darauf hin, dass es mit Einführung einer dualen Therapie aus Ceftriaxon und Azithromycin und dem konsekutiv verminderten Einsatz von Cefixim zu einem Rückgang von Cefixim-resistenten Stämmen gekommen ist.

  • 11.
    Banhart, Sebastian
    et al.
    Unit 'Sexually Transmitted Bacterial Infections', Department for Infectious Diseases, Robert Koch Institute, Berlin, Germany.
    Jansen, Klaus
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Buder, Susanne
    German Reference Laboratory for Gonococci, Department of Dermatology and Venerology, Vivantes Hospital Berlin, Berlin, Germany.
    Tamminga, Thalea
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Calvignac-Spencer, Sébastien
    Project Group 'Epidemiology of Highly Pathogenic Microorganisms', Robert Koch Institute, Berlin, Germany.
    Pilz, Tanja
    Unit 'Sexually Transmitted Bacterial Infections', Department for Infectious Diseases, Robert Koch Institute, Berlin, Germany.
    Martini, Andrea
    Unit 'Sexually Transmitted Bacterial Infections', Department for Infectious Diseases, Robert Koch Institute, Berlin, Germany.
    Dudareva, Sandra
    Charité Universitätsmedizin Berlin, Berlin, Germany; Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Nikisins, Sergejs
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Dehmel, Kerstin
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Zuelsdorf, Gabriele
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Guhl, Eva
    German Reference Laboratory for Gonococci, Department of Dermatology and Venerology, Vivantes Hospital Berlin, Berlin, Germany.
    Graeber, Ingeborg
    German Reference Laboratory for Gonococci, Department of Dermatology and Venerology, Vivantes Hospital Berlin, Berlin, Germany.
    Kohl, Peter K.
    German Reference Laboratory for Gonococci, Department of Dermatology and Venerology, Vivantes Hospital Berlin, Berlin, Germany.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs.
    Bremer, Viviane
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Heuer, Dagmar
    Unit 'Sexually Transmitted Bacterial Infections', Department for Infectious Diseases, Robert Koch Institute, Berlin, Germany.
    GORENET, Study Group
    Molecular epidemiological typing of Neisseria gonorrhoeae isolates identifies a novel association between genogroup G10557 (G7072) and decreased susceptibility to cefixime, Germany, 2014 to 20172020In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 25, no 41, article id 1900648Article in journal (Refereed)
    Abstract [en]

    Background: Emerging antimicrobial resistance (AMR) challenges gonorrhoea treatment and requires surveillance.AimThis observational study describes the genetic diversity of Neisseria gonorrhoeae isolates in Germany from 2014 to 2017 and identifies N. gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroups associated with AMR or some patient demographics.

    Methods: 1,220 gonococcal isolates underwent AMR testing and NG-MAST. Associations between genogroups and AMR or sex/age of patients were statistically assessed.

    Results: Patients' median age was 32 years (interquartile range: 25-44); 1,078 isolates (88.4%) originated from men. In total, 432 NG-MAST sequence types including 156 novel ones were identified, resulting in 17 major genogroups covering 59.1% (721/1,220) of all isolates. Genogroups G1407 and G10557 (G7072) were significantly associated with decreased susceptibility to cefixime (Kruskal-Wallis chi-squared: 549.3442, df: 16, p < 0.001). Their prevalences appeared to decline during the study period from 14.2% (15/106) to 6.2% (30/481) and from 6.6% (7/106) to 3.1% (15/481) respectively. Meanwhile, several cefixime susceptible genogroups' prevalence seemed to increase. Proportions of isolates from men differed among genogroups (Fisher's exact test, p < 0.001), being e.g. lower for G25 (G51) and G387, and higher for G5441 and G2992. Some genogroups differed relative to each other in affected patients' median age (Kruskal-Wallis chi-squared: 47.5358, df: 16, p < 0.001), with e.g. G25 (G51) and G387 more frequent among ≤ 30 year olds and G359 and G17420 among ≥ 40 year olds.

    Conclusion: AMR monitoring with molecular typing is important. Dual therapy (ceftriaxone plus azithromycin) recommended in 2014 in Germany, or only the ceftriaxone dose of this therapy, might have contributed to cefixime-resistant genogroups decreasing.

  • 12.
    Bazzo, M. L.
    et al.
    Molecular Biology, Microbiology and Serology Laboratory, Federal University of Santa Catarina, Florianópolis, Brazil.
    Golfetto, L.
    Molecular Biology, Microbiology and Serology Laboratory, Federal University of Santa Catarina, Florianópolis, Brazil.
    Gaspar, P. C.
    Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Ministry of Health, Brasilia, Brazil.
    Pires, A. F.
    Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Ministry of Health, Brasilia, Brazil; University of Brasilia Postgraduate Program in Collective Health, Brasilia, Brazil.
    Ramos, M. C.
    Brazilian STD Society, Porto Alegre, Brazil.
    Franchini, M.
    Laboratory Consultant, Brasília, Brazil.
    Ferreira, W. A.
    Alfredo da Mata Foundation, Manaus, Brazil.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Benzaken, A. S.
    Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Ministry of Health, Brasilia, Brazil.
    First nationwide antimicrobial susceptibility surveillance for Neisseria gonorrhoeae in Brazil, 2015-162018In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 7, p. 1854-1861Article in journal (Refereed)
    Abstract [en]

    Objectives: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major public health concerns globally. Enhanced AMR surveillance for gonococci is essential worldwide; however, recent quality-assured gonococcal AMR surveillance in Latin America, including Brazil, has been limited. Our aims were to (i) establish the first nationwide gonococcal AMR surveillance, quality assured according to WHO standards, in Brazil, and (ii) describe the antimicrobial susceptibility of clinical gonococcal isolates collected from 2015 to 2016 in all five main regions (seven sentinel sites) of Brazil.

    Methods: Gonococcal isolates from 550 men with urethral discharge were examined for susceptibility to ceftriaxone, cefixime, azithromycin, ciprofloxacin, benzylpenicillin and tetracycline using the agar dilution method, according to CLSI recommendations and quality assured according to WHO standards.

    Results: The levels of resistance (intermediate susceptibility) to tetracycline, ciprofloxacin, benzylpenicillin and azithromycin were 61.6%(34.2%), 55.6%(0.5%), 37.1% (60.4%) and 6.9% (8.9%), respectively. All isolates were susceptible to ceftriaxone and cefixime using the US CLSI breakpoints. However, according to the European EUCAST cefixime breakpoints, 0.2% (n= 1) of isolates were cefixime resistant and 6.9% (n = 38) of isolates had a cefixime MIC bordering on resistance.

    Conclusions: This study describes the first national surveillance of gonococcal AMR in Brazil, which was quality assured according to WHO standards. The high resistance to ciprofloxacin (which promptly informed a revision of the Brazilian sexually transmitted infection treatment guideline), emerging resistance to azithromycin and decreasing susceptibility to extended-spectrum cephalosporins necessitate continuous surveillance of gonococcal AMR and ideally treatment failures, and increased awareness when prescribing treatment in Brazil.

  • 13.
    Beale, M.
    et al.
    Wellcome Sanger Institute, Cambridge, UK.
    Marks, M.
    London School of Hygiene and Tropical Medicine, London, UK.
    Cole, M.
    National Infection Service, Public Health England, London, UK.
    Lee, M.
    British Columbia Centre for Disease Control, Vancouver, Canada.
    Pitt, R.
    National Infection Service, Public Health England, London, UK.
    Ruis, C.
    University of Cambridge Department of Medicine, Cambridge, UK.
    Naidu, P.
    Alberta Precision Laboratories, Edmonton, Canada.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for STI.
    Krajden, M.
    British Columbia Centre for Disease Control, Vancouver, Canada.
    Lukehart, S.
    University of Washington, Seattle, USA.
    Morshed, M.
    British Columbia Centre for Disease Control, Vancouver, Canada.
    Fifer, H.
    National Infection Service, Public Health England, London, UK.
    Thomson, N.
    Wellcome Sanger Institute, Cambridge, UK; London School of Hygiene and Tropical Medicine, London, UK.
    CONTEMPORARY SYPHILIS IS CHARACTERISED BY RAPID GLOBAL SPREAD OF PANDEMIC TREPONEMA PALLIDUM LINEAGES2021In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 97, no Suppl. 1, p. A17-A17, article id O01.8Article in journal (Other academic)
    Abstract [en]

    Background: Syphilis is an important sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. The last two decades have seen syphilis incidence rise in many high-income countries, yet the evolutionary and epidemiological relationships that underpin this are poorly understood, as is the global T. pallidum population structure.

    Methods: We assembled a geographically and temporally diverse collection of clinical and laboratory samples, performing direct sequencing on the majority, and combining these with 133 publicly available sequences to compile a dataset comprising 726 T. pallidum genomes. We analysed the resulting genomes using detailed phylogenetic analysis and clustering.

    Results: We show that syphilis globally can be described by only two deeply branching lineages, Nichols and SS14. We show that both of these lineages can be found circulatingcon currently in 12 of the 23 countries sampled. To provide further phylodynamic resolution we subdivided Treponema pallidum subspecies pallidum into 17 distinct sublineages. Importantly, like SS14, we provide evidence that two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analysis showed that recent isolates circulating in 14 different countries were genetically identical in their core genome to those from other countries, suggesting frequent exchange through international transmission pathways. This contrasts with the majority of samples collected prior to 1983, which are phylogenetically distinct from these more recently isolated sublineages. Bayesian temporal analysis provided evidence of a population bottleneck and decline occurring during the late 1990s, followed by a rapid population expansion a decade later. This was driven by the dominant T. pallidum sublineages circulating today, many of which are resistant to macrolides.

    Conclusion: Combined we show that the population of contemporary syphilis in high-income countries has undergone a recent and rapid global expansion. This dataset will provide a framework for future characterisation and epidemiological investigation of syphilis populations.

  • 14.
    Beale, Mathew A.
    et al.
    Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton, UK.
    Marks, Michael
    Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK; Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK.
    Cole, Michelle J.
    HCAI, Fungal, AMR, AMU and Sepsis Division, UK Health Security Agency, London, UK.
    Lee, Min-Kuang
    British Columbia Centre for Disease Control, Public Health Laboratory, Vancouver, British Columbia, Canada.
    Pitt, Rachel
    HCAI, Fungal, AMR, AMU and Sepsis Division, UK Health Security Agency, London, UK.
    Ruis, Christopher
    Molecular Immunity Unit, MRC-Laboratory of Molecular Biology, Department of Medicine, University of Cambridge, Cambridge, UK; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    Balla, Eszter
    Bacterial STIs Reference Laboratory, Department of Bacteriology, National Public Health Centre, Budapest, Hungary.
    Crucitti, Tania
    Department of Clinical Sciences, Institute of Tropical Medicine, Antwerpen, Belgium.
    Ewens, Michael
    Brotherton Wing, Leeds General Infirmary, Leeds, UK.
    Fernández-Naval, Candela
    Microbiology Department, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
    Grankvist, Anna
    National Reference Laboratory for STIs, Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Guiver, Malcolm
    Laboratory Network, Manchester, UK Health Security Agency, Manchester Royal Infirmary, Manchester, UK.
    Kenyon, Chris R.
    Department of Clinical Sciences, Institute of Tropical Medicine, Antwerpen, Belgium.
    Khairullin, Rafil
    Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
    Kularatne, Ranmini
    Centre for HIV and STI, National Institute for Communicable Diseases, Johannesburg, South Africa.
    Arando, Maider
    STI Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Hospital Vall d'Hebron, Barcelona, Spain.
    Molini, Barbara J.
    Department of Medicine, University of Washington, Seattle, WA, USA.
    Obukhov, Andrey
    Tuvan Republican Skin and Venereal Diseases Dispensary, Ministry of Health of Tuva Republic, Kyzyl, Russia.
    Page, Emma E.
    Virology Department, Old Medical School, Leeds Teaching Hospitals Trust, Leeds, UK.
    Petrovay, Fruzsina
    Bacterial STIs Reference Laboratory, Department of Bacteriology, National Public Health Centre, Budapest, Hungary.
    Rietmeijer, Cornelis
    Colorado School of Public Health, University of Colorado, Denver, CO, USA.
    Rowley, Dominic
    Midlands Regional Hospital Portlaoise, Laois, Ireland.
    Shokoples, Sandy
    Alberta Precision Laboratories, Edmonton, Alberta, Canada.
    Smit, Erasmus
    Clinical Microbiology Department, Queen Elizabeth Hospital, Birmingham, UK; Institute of Environmental Science and Research, Wellington, New Zealand.
    Sweeney, Emma L.
    The University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
    Taiaroa, George
    Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
    Vera, Jaime H.
    Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
    Wennerås, Christine
    National Reference Laboratory for STIs, Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Whiley, David M.
    The University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Pathology Queensland Central Laboratory, Brisbane, Queensland, Australia .
    Williamson, Deborah A.
    Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
    Hughes, Gwenda
    Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
    Naidu, Prenilla
    Alberta Precision Laboratories, Edmonton, Alberta, Canada; Department of Laboratory Medicine and Pathology, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada .
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for STIs, Faculty of Medicine and Health.
    Krajden, Mel
    British Columbia Centre for Disease Control, Public Health Laboratory, Vancouver, British Columbia, Canada; Clinical Microbiology Department, Queen Elizabeth Hospital, Birmingham, UK.
    Lukehart, Sheila A.
    Departments of Medicine/Infectious Diseases and Global Health, University of Washington, Seattle, WA, USA.
    Morshed, Muhammad G.
    British Columbia Centre for Disease Control, Public Health Laboratory, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
    Fifer, Helen
    Blood Safety, Hepatitis, STI and HIV Division, UK Health Security Agency, London, UK.
    Thomson, Nicholas R.
    Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
    Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis2021In: Nature Microbiology, E-ISSN 2058-5276, Vol. 6, no 12, p. 1549-1560Article in journal (Refereed)
    Abstract [en]

    Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p. pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides.

  • 15.
    Berçot, Béatrice
    et al.
    Université Paris Cité, INSERM, IAME, Paris, France; APHP, Infectious Agents Department, Saint Louis Hospital, Paris, France; French National Reference Centre for bacterial STIs, Associated Laboratory for Gonococci, Paris, France.
    Caméléna, François
    Université Paris Cité, INSERM, IAME, Paris, France; APHP, Infectious Agents Department, Saint Louis Hospital, Paris, France; French National Reference Centre for bacterial STIs, Associated Laboratory for Gonococci, Paris, France.
    Mérimèche, Manel
    Université Paris Cité, INSERM, IAME, Paris, France; APHP, Infectious Agents Department, Saint Louis Hospital, Paris, France; French National Reference Centre for bacterial STIs, Associated Laboratory for Gonococci, Paris, France.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Ӧrebro University, Ӧrebro, Sweden.
    Sbaa, Ghalia
    APHP, Infectious Agents Department, Saint Louis Hospital, Paris, France; French National Reference Centre for bacterial STIs, Associated Laboratory for Gonococci, Paris, France.
    Mainardis, Mary
    APHP, Infectious Agents Department, Saint Louis Hospital, Paris, France; French National Reference Centre for bacterial STIs, Associated Laboratory for Gonococci, Paris, France.
    Valin, Cyrille
    Laboratoire Anse, Biogroup, Lyon, France.
    Molina, Jean-Michel
    AP-HP, Hôpital Saint-Louis, Lariboisière, Département de Maladies Infectieuses et Tropicales, Paris, France; Université Paris Cité, UMR S976, INSERM, Paris, France.
    Bébéar, Cécile
    University of Bordeaux, USC EA 3671, Mycoplasmal and Chlamydial Infections in Humans, Bordeaux University Hospital, French National Reference Centre for Bacterial STIs, Bordeaux, France.
    Chazelle, Emilie
    Santé Publique France, French National Public Health Agency, Saint-Maurice, France.
    Lot, Florence
    Santé Publique France, French National Public Health Agency, Saint-Maurice, France.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Ӧrebro University, Ӧrebro, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Ӧrebro University, Ӧrebro, Sweden; Institute for Global Health, University College London, London, United Kingdom .
    Ceftriaxone-resistant, multidrug-resistant Neisseria gonorrhoeae with a novel mosaic penA-237.001 gene, France, June 20222022In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 27, no 50, p. 17-22Article in journal (Refereed)
    Abstract [en]

    We report a ceftriaxone-resistant, multidrug-resistant urogenital gonorrhoea case in a heterosexual woman in France, June 2022. The woman was successfully treated with azithromycin 2 g. She had unprotected sex with her regular partner, who developed urethritis following travel to Vietnam and Switzerland. Whole genome sequencing of the gonococcal isolate (F92) identified MLST ST1901, NG-STAR CC- 199, and the novel mosaic penA-237.001, which caused ceftriaxone resistance. penA-237.001 is 98.7% identical to penA-60.001, reported in various ceftriaxone-resistant strains, including the internationally spreading FC428 clone.

  • 16.
    Bettoni, Serena
    et al.
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Maziarz, Karolina
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Stone, M. Rhia L.
    Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD, Australia.
    Blaskovich, Mark A. T.
    Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD, Australia.
    Potempa, Jan
    Faculty of Biochemistry, Biophysics and Biotechnology, Jagiel- lonian University, Krakow, Poland. Department of Oral Immunity and Infectious Diseases, University of Louisville School of Dentistry, Louisville KY, United States.
    Bazzo, Maria Luiza
    Molecular Biology, Microbiology and Serology Laboratory, Federal University of Santa Catarina, Florianopolis, Brazil.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization (WHO) Collaborating Centre for Gonorrhoea and other STIs.
    Ram, Sanjay
    Department of Medicine, Division of Infectious Diseases, Univer- sity of Massachusetts Medical School, Worcester MA, United States.
    Blom, Anna M.
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Serum complement activation by C4BP-IgM fusion protein can restore susceptibility to antibiotics in Neisseria gonorrhoeae2022In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 141, p. 215-215Article in journal (Other academic)
    Abstract [en]

    Background: The sexually transmitted infection gonorrhea is a common health problem worldwide causing critical reproductive sequelae such as infertility. An effective vaccine remains elusive and antibiotics used in clinics are becoming ineffective because of the rapid spread of resistance among Neisseria gonorrhoeae, the causative organism of gonorrhea. We previously created a human fusion protein called C4BP-IgM to mark and eliminate bacteria by activating host complement. C4BP-IgM links the two N-terminal domains of C4BP, which bind to gonococci, with the Fc domain of IgM to increase complement activation on and kill bacteria. We documented that C4BP-IgM enhances bactericidal activity of serum against clinical C4BP-binding gonococcal isolates from patients, and markedly attenuated the duration and burden of gonococcal infection in a mouse vaginal colonizationmodel 1. Here, we explore the activity of C4BP-IgM as an adjuvant to several antibiotics (spectinomycin, azithromycin, cefixime, ceftriaxone and ciprofloxacin) currently or previously used to treat gonorrhea.

    Materials and methods: Cooperative bactericidal activity between C4BP-IgM, complement and antibiotics was evaluated by monitoring survival and membrane alterations of a laboratory isolate and two clinical azithromycin-resistant gonococcal strains, which also resisted killing by normal human serum. Effect of complement and C4BP-IgM on uptake and intracellular activity of selected antibiotics was also assessed.

    Results: We found that human serum, as source of complement components, reduced MIC values of antibiotics against N. gonorrhoeae. Addition of C4BP-IgM at concentrations which only partially reduced survival, induced complete killing of bacteria when both serum and antibiotics were present. Bactericidal cooperation between complement and antimicrobials was revealed to be triggered by membrane damage induced by C4BP-IgM complement activation. Formation of membrane attack complex pores on bacteria facilitated uptake of antimicrobials, which in turn enhanced their intracellular concentration and activity. Remarkably, C4BP-IgM restored susceptibility to azithromycin of two azithromycin-resistant clinical gonococcal strains that overexpressed the MtrC-MtrD-MtrE efflux pump.

    Conclusion: We provide proof-of-principle for the use of C4BP-IgM fusion protein as an adjuvant to antibiotics, which could be re-purposed for clinical use pending the development of effective new treatments.

  • 17.
    Bettoni, Serena
    et al.
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Maziarz, Karolina
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Stone, M. Rhia L.
    Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
    Blaskovich, Mark A. T.
    Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
    Potempa, Jan
    Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; Department of Oral Immunity and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United States.
    Bazzo, Maria Luiza
    Molecular Biology, Microbiology and Serology Laboratory, Federal University of Santa Catarina, Florianópolis, Brazil.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization (WHO) Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    Ram, Sanjay
    Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA, United States.
    Blom, Anna M.
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Serum Complement Activation by C4BP-IgM Fusion Protein Can Restore Susceptibility to Antibiotics in Neisseria gonorrhoeae2021In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 12, article id 726801Article in journal (Refereed)
    Abstract [en]

    Neisseria gonorrhoeae is the etiological agent of gonorrhea, the second most common bacterial sexually transmitted infection worldwide. Reproductive sequelae of gonorrhea include infertility, ectopic pregnancy and chronic pelvic pain. Most antibiotics currently in clinical use have been rendered ineffective due to the rapid spread of antimicrobial resistance among gonococci. The developmental pipeline of new antibiotics is sparse and novel therapeutic approaches are urgently needed. Previously, we utilized the ability of N. gonorrhoeae to bind the complement inhibitor C4b-binding protein (C4BP) to evade killing by human complement to design a chimeric protein that linked the two N-terminal gonococcal binding domains of C4BP with the Fc domain of IgM. The resulting molecule, C4BP-IgM, enhanced complement-mediated killing of gonococci. Here we show that C4BP-IgM induced membrane perturbation through complement deposition and membrane attack complex pore insertion facilitates the access of antibiotics to their intracellular targets. Consequently, bacteria become more susceptible to killing by antibiotics. Remarkably, C4BP-IgM restored susceptibility to azithromycin of two azithromycin-resistant clinical gonococcal strains because of overexpression of the MtrC-MtrD-MtrE efflux pump. Our data show that complement activation can potentiate activity of antibiotics and suggest a role for C4BP-IgM as an adjuvant for antibiotic treatment of drug-resistant gonorrhea.

  • 18.
    Bettoni, Serena
    et al.
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Shaughnessy, Jutamas
    Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
    Maziarz, Karolina
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Ermert, David
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Gulati, Sunita
    Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
    Zheng, Bo
    Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
    Mörgelin, Matthias
    Colzyx, Lund, Sweden.
    Jacobsson, Susanne
    World Health Organization (WHO) Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Örebro University, Örebro, Sweden.
    Riesbeck, Kristian
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization (WHO) Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    Ram, Sanjay
    Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
    Blom, Anna M.
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    C4BP-IgM protein as a therapeutic approach to treat Neisseria gonorrhoeae infections2019In: JCI Insight, ISSN 2379-3708, Vol. 4, no 23, article id 131886Article in journal (Refereed)
    Abstract [en]

    Gonorrhea is a sexually transmitted infection with 87 million new cases per year globally. Increasing antibiotic resistance has severely limited treatment options. A mechanism that Neisseria gonorrhoeae uses to evade complement attack is binding of the complement inhibitor C4b-binding protein (C4BP). We screened 107 porin B1a (PorB1a) and 83 PorB1b clinical isolates randomly selected from a Swedish strain collection over the last 10 years and noted that 96/107 (89.7%) PorB1a and 16/83 (19.3%) PorB1b bound C4BP; C4BP binding substantially correlated with the ability to evade complement-dependent killing (r = 0.78). We designed 2 chimeric proteins that fused C4BP domains to the backbone of IgG or IgM (C4BP-IgG; C4BP-IgM) with the aim of enhancing complement activation and killing of gonococci. Both proteins bound gonococci (KD C4BP-IgM = 2.4 nM; KD C4BP-IgG 980.7 nM), but only hexameric C4BP-IgM efficiently outcompeted heptameric C4BP from the bacterial surface, resulting in enhanced complement deposition and bacterial killing. Furthermore, C4BP-IgM substantially attenuated the duration and burden of colonization of 2 C4BP-binding gonococcal isolates but not a non-C4BP-binding strain in a mouse vaginal colonization model using human factor H/C4BP-transgenic mice. Our preclinical data present C4BP-IgM as an adjunct to conventional antimicrobials for the treatment of gonorrhea.

  • 19.
    Bettoni, Serena
    et al.
    Lund University - Department of Translational Medicine, Malmö, Sweden.
    Shaughnessy, Jutamas
    Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, USA.
    Maziarz, Karolina
    Lund University - Department of Translational Medicine, Malmö, Sweden.
    Ermert, David
    Lund University - Department of Translational Medicine, Malmö, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Riesbeck, Kristian
    Lund University - Department of Translational Medicine, Malmö, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Blom, Anna
    Lund University - Department of Translational Medicine, Malmö, Sweden.
    Ram, Sanjay
    Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, USA.
    C4BP-IGM FUSION PROTEIN AS A NOVEL THERAPEUTIC APPROACH TO TREAT NEISSERIA GONORRHOEAE INFECTIONS2019In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 114, p. 470-470Article in journal (Other academic)
  • 20.
    Bignell, C.
    et al.
    City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
    Unemo, Magnus
    Örebro University Hospital. WHO Collaborating Center for Gonorrhoea and Other Sexually Transmitted Infections, , Örebro University Hospital, Örebro, Sweden; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    2012 European guideline on the diagnosis and treatment of gonorrhoea in adults [Europejskie zalecenia diagnostyczne i terapeutyczne w rzeÅŒa̧czce u dorosłych, 2012]2014In: Przegląd Dermatologiczny, ISSN 0033-2526, Vol. 101, no 2, p. 168-178Article in journal (Refereed)
  • 21.
    Bignell, Chris J.
    et al.
    City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, UK.
    Unemo, Magnus
    WHO Collaborating Center for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    2012 European guideline on the diagnosis and treatment of gonorrhoea in adults2013In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 24, no 2, p. 85-92Article in journal (Refereed)
    Abstract [en]

    Gonorrhoea is a major public health concern globally. Of particularly grave concern is that resistance to the extended-spectrum cephalosporins has emerged during the most recent years. This guideline provides recommendations regarding the diagnosis and treatment of gonorrhoea in Europe. Compared to the outdated 2009 European gonorrhoea guideline, this 2012 European gonorrhoea guideline provides up-to-date guidance on, broader indications for testing and treatment of gonorrhoea; the introduction of dual antimicrobial therapy (ceftriaxone 500 mg and azithromycin 2 g) for uncomplicated gonorrhoea when the antimicrobial sensitivity is unknown; recommendation of test of cure in all gonorrhoea cases to ensure eradication of infection and identify emerging resistance; and recommendations to identify, verify and report failures with recommended treatment regimens. Optimisations of the testing, diagnostics, antimicrobial treatment and follow-up of gonorrhoea patients are crucial in controlling the emergent spread of cephalosporin-resistant and multidrug-resistant gonorrhoea.

  • 22.
    Birhanu, Muluken
    et al.
    Department of Medical Laboratory Science, College of Health Science, Assosa University, Assosa, Ethiopia; Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
    Abegaz, Woldaregay Erku
    Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
    Schröder, Daniel
    Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University, Örebro, Sweden.
    Mihret, Adane
    Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Department of Bacteriology, Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
    Abebe, Tamrat
    Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and Other STIs.
    Tasew, Geremew
    National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia.
    Addis, Tesfa
    National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia.
    Abdeta, Abera
    National Clinical Bacteriology and Mycology Reference Laboratory, Ethiopian Public Health Institute, Addis Ababa, Ethiopia.
    Alem, Yonas
    Department of Medical Laboratory Sciences, Ambo University, Ambo, Ethiopia.
    Desalegn, Zelealem
    Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
    Ademe, Muluneh
    Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
    Teka, Birhanu
    Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
    Yohannes, Meron
    Department of Medical Laboratory Science, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
    Yigeremus, Mahlet
    Department of Gynecology and Obstetrics, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University, Örebro, Sweden.
    Gebre-Selassie, Solomon
    Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University, Örebro, Sweden; Institute for Global Health, University College London (UCL), London, UK.
    Antimicrobial susceptibility in Neisseria gonorrhoeae and epidemiological data of gonorrhoea patients in five cities across Ethiopia, 2021-222024In: JAC-antimicrobial resistance, E-ISSN 2632-1823, Vol. 6, no 1, article id dlae002Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern and enhanced global gonococcal AMR surveillance is imperative. As in many African countries, regular, representative and quality-assured gonococcal AMR is lacking in Ethiopia. We describe the AMR in gonococcal isolates from five cities across Ethiopia, 2021-22, and patient epidemiological data.

    METHODS: Urethral discharge from males and cervical discharge from females were collected from October 2021 to September 2022. Epidemiological data were collected using a questionnaire. MIC determination (ETEST; eight antimicrobials) was performed on gonococcal isolates and EUCAST breakpoints (v13.1) were used.

    RESULTS: From 1142 urogenital swab samples, 299 species-identified gonococcal isolates were identified; 78.3% were from males and 21.7% from females. The median age for males and females was 25 and 23 years, respectively. Most isolates (61.2%) were identified in Addis Ababa, followed by Gondar (11.4%), Adama (10.4%), Bahir Dar (10.0%) and Jimma (7.0%). The resistance level to ciprofloxacin, tetracycline and benzylpenicillin was 97.0%, 97.0% and 87.6%, respectively, and 87.6% of isolates were producing β-lactamase. All isolates were susceptible to ceftriaxone, cefixime, azithromycin and spectinomycin. Recommended therapy [ceftriaxone (250 mg) plus azithromycin (1 g)] was used for 84.2% of patients.

    CONCLUSIONS: We present the first national quality-assured gonococcal AMR data from Ethiopia. Resistance levels to ciprofloxacin, tetracycline and benzylpenicillin were exceedingly high. However, all isolates were susceptible to ceftriaxone, cefixime, azithromycin and spectinomycin. In Ethiopia, it is essential to strengthen the gonococcal AMR surveillance by including further epidemiological data, more isolates from different cities, and WGS.

  • 23.
    Boiko, Iryna
    et al.
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine; WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Krynytska, Inna
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine.
    Frankenberg, Arkadii
    Dnipro Regional Dermatovenerologic Dispensary, Dnipro, Ukraine.
    Shevchenko, Tetiana
    Department of General Medicine with a Course of Physical Therapy, Faculty of Medical Technologies of Diagnostics and Rehabilitation, Oles Honchar Dnipro National University, Dnipro, Ukraine.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health.
    Genomic epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates from Ukraine, 2013-20182020In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 128, no 7, p. 465-475Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major health threat compromising the gonorrhoea treatment globally. AMR surveillance including whole genome sequencing (WGS)-based epidemiology provides ideal resolution to identify and describe AMR gonococcal clones, AMR determinants and populations, which can inform management guidelines and antimicrobial stewardship policies. Our aims were to, for the first time, elucidate the WGS-based epidemiology and characterise AMR determinants of gonococcal strains spreading in Ukraine, 2013-2018. Gonococcal isolates (n=150) from Ternopil and Dnipro, Ukraine (2013-2018) were subjected to AMR testing (Etest) for eight antimicrobials and WGS. Overall, 11.3% of isolates were resistant to ciprofloxacin, 6.0% to tetracycline and 0.7% to benzylpenicillin. No isolates were resistant to azithromycin, spectinomycin, ceftriaxone, or cefixime, but one isolate was bordering resistance to both cephalosporins. Twenty-five MLST STs, 50 NG-MAST STs, and 34 NG-STAR types were identified. The phylogenomic analysis revealed six main clusters, mostly associated with the internationally described multidrug-susceptible gonococcal lineage. Resistance to ciprofloxacin was associated with GyrA S91F and ParC S87R mutations; tetracyclines with rpsJ V57M and tetM; penicillins with mosaic penA-34.001 and β-lactamase; mtrR; PorB1b G101D, and PBP1 L421P mutations. One isolate of the multidrug-resistant NG-MAST ST1407, MLST ST1901 was found, which was bordering resistance to ceftriaxone and cefixime. The susceptibility of gonococcal strains spreading in Ternopil and Dnipro, Ukraine, 2013-2018 was surprisingly high. Continued and expanded gonococcal AMR surveillance, ideally including WGS, in Ukraine is essential. This could inform action plans and public health policies to control the spread of AMR gonococcal strains in Ukraine.

  • 24.
    Boiko, Iryna
    et al.
    Ternopil Regional Clinical Dermatovenerologic Dispensary, Clinical Laboratory Department, Ternopil, Ukraine; Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine; WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Krynsytska, Inna
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    High prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae and particularly Trichomonas vaginalis diagnosed using US FDA-approved Aptima molecular tests and evaluation of conventional routine diagnostic tests in Ternopil, Ukraine2019In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 9, p. 627-634Article in journal (Refereed)
    Abstract [en]

    Sexually transmitted infections (STIs) remain major public health problems globally. Appropriate laboratory diagnosis of STIs is rare in Ukraine. We investigated the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) using the US FDA-approved Aptima Combo 2 and Aptima TV assays and compared the results with the conventional routine diagnostic tests (CDTs) in Ukraine. Urogenital swabs from consecutive mostly symptomatic females (n = 296) and males (n = 159) were examined. The prevalences were as follows: 10% (n = 47) of TV, 5.3% (n = 24) of CT and 1.5% (n = 7) of NG. The specificity of some CDTs was high, for example, 100% for NG culture, TV IgG ELISA, CT IgM ELISA and CT microscopy, but lower for other CDTs, that is, from 44% to 99.8%. The sensitivity of all CDTs was suboptimal, that is, 71% (n = 5) for NG microscopy, 57% (n = 4) for NG culture, 53% (n = 8) for CT IgG ELISA, 33% (n = 1) for TV IgG ELISA, 28% (n = 13) for TV microscopy, 25% (n = 1) for CT IgA ELISA, 20% (n = 3) for CT IgM ELISA and 0% (n = 0) for CT microscopy. The prevalences of particularly TV and CT were high, but substantial also for NG, in Ternopil, Ukraine. The sensitivities of all CDTs were low, and widespread implementation of validated, quality-assured and cost-effective molecular diagnostic STI tests in Ukraine is imperative.

  • 25.
    Boiko, Iryna
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Clinical Laboratory Department, Ternopil Regional Clinical Dermatovenerologic Dispensary, Ternopil, Ukraine.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Krynytska, Inna
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine.
    Bezkorovaina, Halyna
    Outpatient Department, Ternopil Regional Clinical Dermatovenerologic Dispensary, Ternopil, Ukraine.
    Frankenberg, Arkadii
    Dnipropetrovsk Regional Clinical Dermatovenerologic Dispensary, Dnipro, Ukraine.
    Onuchyna, Margarita
    Clinical Laboratory Department, Dnipropetrovsk Regional Clinical Dermatovenerologic Dispensary, Dnipro, Ukraine.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-20182019In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 7, p. 503-509Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern globally. However, recent gonococcal AMR data from Eastern Europe are extremely limited and no AMR data for strains spreading in Ukraine have ever been internationally published. We investigated the AMR of N. gonorrhoeae isolates in two regions of Ukraine (Ternopil 2013-2018, Dnipropetrovsk 2013-2014), and, where information was available, the treatment administered to the corresponding gonorrhoea patients. Determination of minimum inhibitory concentration (MIC) of eight antimicrobials was performed using Etest and resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were applied. Overall, 9.3% of the examined 150 isolates were resistant to ciprofloxacin, 6.0% to tetracycline, 2.0% to azithromycin, and 0.7% to benzylpenicillin. No isolates were resistant to ceftriaxone, cefixime, spectinomycin, or gentamicin. However, one (0.7%) isolate showed a MIC value of 0.125 mg/L for both ceftriaxone and cefixime, i.e., bordering resistance. Eighty-eight (67.2%) of 131 patients were administered dual therapy (ceftriaxone 1 g plus doxycycline/clarithromycin/azithromycin/ofloxacin) and 22 (16.8%) ceftriaxone 1 g monotherapy. Worryingly, 21 (16.0%) patients received monotherapy with clarithromycin/doxycycline/azithromycin/ofloxacin/benzylpenicillin. In conclusion, the antimicrobial susceptibility of gonococcal strains spreading in Ternopil and Dnipropetrovsk, Ukraine during 2013-2018 was high. Low levels of resistance to ciprofloxacin, tetracycline, azithromycin, and benzylpenicillin were found, but no resistance to the internationally recommended ceftriaxone, cefixime, or spectinomycin. Ceftriaxone 1 g should remain as empiric first-line treatment, in dual therapy with azithromycin or doxycycline or in monotherapy. Continued and expanded gonococcal AMR surveillance in Ukraine is essential to monitor the susceptibility to particularly extended-spectrum cephalosporins, azithromycin and doxycycline.

  • 26.
    Brendefur Corwin, L. M.
    et al.
    Department of Microbiology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Campbell, P.
    Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway; National Advisory Unit for Sexually Transmitted Infections, Oslo University Hospital, Oslo, Norway.
    Jakobsen, K.
    Department of Microbiology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Müller, F.
    Department of Microbiology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Lai, X
    Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Institute for Global Health, University College London (UCL), London, UK.
    Leegaard, T. M.
    Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Microbiology and Infection Control, Akershus University Hospital, Lørenskog, Norway.
    Vildershøj Bjørnholt, J.
    Department of Microbiology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Olsen, A. O.
    Section for Respiratory, Blood-borne and Sexually Transmitted Infections, Department of Infection Control and Vaccines, Norwegian Institute of Public Health, Oslo, Norway; Department of Community Medicine and Global Health, Institute of Health and Society, University of Oslo, Oslo, Norway.
    Improvement in Neisseria gonorrhoeae culture rates by bedside inoculation and incubation at a clinic for sexually transmitted infections2023In: Annals of Clinical Microbiology and Antimicrobials, E-ISSN 1476-0711, Vol. 22, no 1, article id 27Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Culture of Neisseria gonorrhoeae is essential for surveillance of complete antimicrobial susceptibility profiles. In 2014, the culture success rate of N. gonorrhoeae from samples taken at the clinic for sexually transmitted infections (STI clinic), Oslo University Hospital, Norway, was only 20%. The present study aimed to improve gonococcal culture rates using bedside inoculation of patient samples on gonococcal agar plates and incubation at the STI clinic.

    METHODS: This prospective quality improvement study was conducted by the STI clinic and the Department of Microbiology at Oslo University Hospital from May 2016 - October 2017. When culture of N. gonorrhoeae was clinically indicated, we introduced a parallel 'bedside culture' at the STI clinic and compared results with the standard culture at the microbiology department. Samples were taken from urethra, anorectum, pharynx and cervix. Culture rates were compared across symptomatic and asymptomatic anatomical sites.

    RESULTS: From 596 gonococcal-positive PCR samples, bedside culture had a significantly higher success rate of 57% compared to 41% with standard culture (p < 0.05). Overall, culture rate from symptomatic sites was 91% v. 45% from asymptomatic sites. The culture rates from different anatomical sites were as follows: urethra 93%, anorectum 64%, pharynx 28% and cervix 70%. Bedside culture significantly (p < 0.05) improved the culture rates for symptomatic urethral and asymptomatic pharyngeal samples.

    CONCLUSIONS: Where feasible, bedside inoculation on gonococcal agar plates and incubation of samples from patients with gonorrhoea is recommended. This will improve the culture diagnostics and provide additional gonococcal isolates for antimicrobial resistance surveillance.

  • 27.
    Bruni, Mirian Pinheiro
    et al.
    Biology Institute, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    Freitas da Silveira, Mariangela
    School of Medicine, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    Stauffert, Dulce
    School of Medicine, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    Bicca, Guilherme Lucas de Oliveira
    School of Medicine, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    Caetano Dos Santos, Carolina
    Biology Institute, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    da Rosa Farias, Nara Amélia
    Biology Institute, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    Aptima Trichomonas vaginalis assay elucidates significant underdiagnosis of trichomoniasis among women in Brazil according to an observational study2019In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, no 2, p. 129-132Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Trichomonas vaginalis (TV) infection is the most common non-viral STI globally and can result in adverse pregnancy outcomes and exacerbated HIV acquisition/transmission. Nucleic acid amplification tests (NAATs) are the most sensitive diagnostic tests, with high specificity, but TV NAATs are rarely used in Brazil. We investigated the TV prevalence and compared the performance of the US Food and Drug Association-cleared Aptima TV assay with microscopy (wet mount and Gram-stained) and culture for TV detection in women in Pelotas, Brazil in an observational study.

    METHODS: From August 2015 to December 2016, 499 consecutive asymptomatic and symptomatic sexually active women attending a Gynaecology and Obstetrics Outpatient Clinic were enrolled. Vaginal fluid and swab specimens were collected and wet mount microscopy, Gram-stained microscopy, culture and the Aptima TV assay performed.

    RESULTS: The median age of enrolled women was 36.5 years (range: 15-77). The majority were white, had a steady sexual partner and low levels of education. The TV detection rate was 4.2%, 2.4%, 1.2% and 0% using the Aptima TV assay, culture, wet mount microscopy and Gram-stained microscopy, respectively. The sensitivity of culture and wet mount microscopy was only 57.1% (95% CI 36.5 to 75.5) and 28.6% (95% CI 13.8 to 50.0), respectively.

    CONCLUSIONS: was found among women in Pelotas, Brazil and the routine diagnostic test (wet mount microscopy) and culture had low sensitivities. More sensitive diagnostic tests (NAATs) and enhanced testing of symptomatic and asymptomatic at-risk women are crucial to mitigate the transmission of TV infection, TV-associated sequelae and enhanced HIV acquisition and transmission.

  • 28.
    Bugaytsova, Jeanna A.
    et al.
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Björnham, Oscar
    Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden; Swedish Defence Research Agency, Umeå, Sweden.
    Chernov, Yevgen A.
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Gideonsson, Pär
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Henriksson, Sara
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden; Umeå Core Facil Electron Microscopy UCEM, Umeå University, Umeå, Sweden.
    Mendez, Melissa
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Sjöström, Rolf
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Mahdavi, Jafar
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden; School of Life Sciences, CBS, University of Nottingham, Nottingham, United Kingdom.
    Shevtsova, Anna
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Ilver, Dag
    Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Acreo Swedish ICT AB, Gothenburg, Sweden.
    Moonens, Kristof
    Structural and Molecular Microbiology, VIB Department of Structural Biology, Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium .
    Quintana-Hayashi, Macarena P.
    Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Moskalenko, Roman
    Department of Pathology, Medical Institute, Sumy State University, Sumy, Ukraine.
    Aisenbrey, Christopher
    Department of Chemistry, Umeå University, Umeå, Sweden; Inst Chim, Univ Strasbourg, Strasbourg, France.
    Bylund, Göran
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Schmidt, Alexej
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden; Dept Med Biosci, Umeå Univ, Umeå, Sweden.
    Åberg, Anna
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Brännström, Kristoffer
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Königer, Verena
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany.
    Vikström, Susanne
    Department of Medical Biochemistry and Biophysics & Faculty Science and Technology, Umeå University, Umeå, Sweden.
    Rakhimova, Lena
    Department of Chemistry, Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Hofer, Anders
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Ögren, Johan
    Department of Odontology, Umeå University, Umeå, Sweden.
    Liu, Hui
    Department of Medicine, USUHS, Bethesda MD, United States.
    Goldman, Matthew D.
    Department of Pediatrics, USUHS, Bethesda MD, United States.
    Whitmire, Jeannette M.
    Department of Microbiology and Immunology, USUHS, Bethesda MD, United States.
    Ådén, Jörgen
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Younson, Justine
    Dental Institute, King's College London, London, United Kingdom.
    Kelly, Charles G.
    Dental Institute, King's College London, London, United Kingdom.
    Gilman, Robert H.
    Department of International Health, John Hopkins School of Public Health, Baltimore MD, United States.
    Chowdhury, Abhijit
    Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India.
    Mukhopadhyay, Asish K.
    Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
    Nair, G. Balakrish
    Translational Health Science and Technology Institute, Haryana, India; WHO Research Policy & Cooperation Unit, New Delhi, India.
    Papadakos, Konstantinos S.
    Hellenic Pasteur Institute, Athens, Greece; Department of Translational Medicine, Wallenberg Lab, Lund University, Malmö, Sweden.
    Martinez-Gonzalez, Beatriz
    Hellenic Pasteur Institute, Athens, Greece.
    Sgouras, Dionyssios N.
    Hellenic Pasteur Institute, Athens, Greece.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Sci Life Lab, Solna, Sweden.
    Unemo, Magnus
    Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Danielsson, Dan
    Örebro University Hospital. Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Suerbaum, Sebastian
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany ; Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Hannover, Germany; German Center for Infection Research (DZIF), Munich, Germany.
    Oscarson, Stefan
    Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Dublin, Ireland.
    Morozova-Roche, Ludmilla A.
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Olofsson, Anders
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Gröbner, Gerhard
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Holgersson, Jan
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
    Esberg, Anders
    Department of Odontology, Umeå University, Umeå, Sweden.
    Strömberg, Nicklas
    Department of Odontology, Umeå University, Umeå, Sweden.
    Landström, Maréne
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany.
    Eldridge, Angela M.
    Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento CA, United States; Genentech Inc, Vacaville CA, USA.
    Chromy, Brett A.
    Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento CA, United States ; Singulex Inc, Alameda CA, USA.
    Hansen, Lori M.
    Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California Davis, Davis CA, United States.
    Solnick, Jay V.
    Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California, Davis CA, United States; California National Primate Research Center, University of California, Davis CA, USA .
    Lindén, Sara K.
    Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Haas, Rainer
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany; German Center for Infection Research (DZIF), Munich, Germany .
    Dubois, Andre
    Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda MD, United States.
    Merrell, D. Scott
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda MD, United States.
    Schedin, Staffan
    Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden.
    Remaut, Han
    Structural and Molecular Microbiology, VIB Department of Structural Biology, Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium .
    Arnqvist, Anna
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Berg, Douglas E.
    Department of Medicine, University of California San Diego, La Jolla CA, United States.
    Borén, Thomas
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence2017In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, no 3, p. 376-389, article id S1931-3128(17)30075-6Article in journal (Refereed)
    Abstract [en]

    The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.

  • 29.
    Bížová, B.
    et al.
    Dermatovenereology Department, Second Faculty of Medicine, Charles University, University Hospital Bulovka, Prague, Czech Republic.
    Procházka, P.
    Venereology Prague, Medicentrum Beroun, Prague, Czech Republic.
    Nyčová, E.
    Department of Microbiology, University Hospital Bulovka, Prague, Czech Republic.
    Bořil, P.
    Clinical Laboratory, Medicentrum Beroun, Beroun, Czech Republic.
    Kubele, J.
    Clinical Microbiology and ATB centre, Na Homolce Hospital, Prague, Czech Republic.
    Poláková, A.
    Department of Microbiology, University Hospital Bulovka, Prague, Czech Republic.
    Zemanová, Z.
    Clinical Microbiology and ATB centre, Na Homolce Hospital, Prague, Czech Republic.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Faculty of Medicine of Health, Örebro University, Örebro, Sweden; Institute for Global Health, University College London, London, United Kingdom.
    Rob, F.
    Dermatovenereology Department, Second Faculty of Medicine, Charles University, University Hospital Bulovka, Prague, Czech Republic.
    Single-dose cefixime 800 mg plus doxycycline 100 mg b.i.d. for 7 days compared to single-dose ceftriaxone 1 g plus single-dose azithromycin 2 g for treatment of urogenital, rectal and pharyngeal gonorrhoea: A randomised clinical trial2024In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 30, no 2, p. 211-215Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the efficacy and tolerability of single-dose oral cefixime 800 mg plus oral doxycycline 100 mg b.i.d. for 7 days, compared to recommended single-dose ceftriaxone plus single-dose, oral azithromycin, for treatment of uncomplicated urogenital, rectal or pharyngeal gonorrhoea.

    METHODS: A non-inferiority, open-label, multicentre randomised controlled trial was conducted in Prague, Czech Republic. Some 161 patients, 18-65 years of age diagnosed with uncomplicated urogenital, rectal or pharyngeal gonorrhoea by nucleic acid amplification test (NAAT) were randomised to treatment with single-dose cefixime 800 mg plus doxycycline 100 mg b.i.d. for 1 week or single-dose ceftriaxone 1 g intramuscularly plus single-dose azithromycin 2 g. The primary outcome was the number of participants with negative culture and NAAT at 1 week and 3 weeks, respectively, after treatment initiation.

    RESULTS: In all, 161 patients were randomised, 152 were included in per-protocol analyses. All 76 (100%; 95% confidence interval [CI], 0.95-1.00) patients treated with ceftriaxone plus azithromycin achieved negative cultures and NAAT after treatment. In the cefixime plus doxycycline arm at week 1, culture was negative in all 76 (100%) patients; at week 3, culture was negative in 70/76 patients (92%; 95%CI, 0.84-0.97) and NAAT negative in 66/76 patients (87%; 95%CI, 0.77-0.94). At week 3, culture and NAAT were negative in 65/76 patients (86%; 95%CI, 0.76-0.93). Per-protocol risk difference was 14.5% (95%CI, 6.56-22.38). All treatment failures observed in the cefixime arm were pharyngeal gonorrhoea cases.

    CONCLUSION: The combination of cefixime and doxycycline did not achieve non-inferiority to ceftriaxone and azithromycin for treatment of gonorrhoea when including pharyngeal gonorrhoea. It did, however, show high efficacy for urogenital and rectal gonorrhoea.

  • 30.
    Cameron-McDermott, Suzette M.
    et al.
    Department of Microbiology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica.
    Barrow, Geoffrey J.
    Department of Medicine, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica.
    Webster, Alicia M.
    Comprehensive Health Centre STI Clinic, Kingston, Jamaica.
    De La Haye, Carrington O.
    Comprehensive Health Centre STI Clinic, Kingston, Jamaica.
    Wood, Denise H. E.
    Comprehensive Health Centre STI Clinic, Kingston, Jamaica.
    Lewis, Violet M.
    Comprehensive Health Centre STI Clinic, Kingston, Jamaica.
    Nicholson, Alison
    Department of Microbiology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica.
    Reynolds-Campbell, Glendee Y.
    Department of Microbiology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica.
    Thoms-Rodriguez, Camille-Ann A.
    Department of Microbiology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica.
    Roye-Green, Karen J.
    Department of Microbiology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica.
    Otto-Stewart, Nakeisha
    Department of Microbiology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica.
    Miller, Zahra N.
    Epidemiology Unit, Ministry of Health and Wellness, Kingston, Jamaica.
    Tomlinson, Jennifer A.
    HIV/STI/TB Unit, Ministry of Health and Wellness, Kingston, Jamaica; Jamaica AIDS Support for Life, Kingston, Jamaica.
    Skyers, Nicola
    HIV/STI/TB Unit, Ministry of Health and Wellness, Kingston, Jamaica.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine.
    Anzinger, Joshua J.
    Department of Microbiology, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica.
    Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and syndromic treatment of men with urethral discharge in Kingston, Jamaica, 2018-192022In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 77, no 1, p. 218-222Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To quantitatively determine the antimicrobial susceptibility of clinical Neisseria gonorrhoeae isolates from men with urethral discharge in Jamaica and to describe the syndromic treatment therapies administered.

    METHODS: Urethral eSwabs (Copan) were collected from 175 men presenting with urethral discharge to the Comprehensive Health Centre STI Clinic, Kingston, Jamaica. Clinical information was collected and MICs of eight antimicrobials were determined for N. gonorrhoeae isolates (n = 96) using Etest and interpreted using CLSI criteria.

    RESULTS: The median age of the subjects was 28 years (range: 18-73 years) with a median of 2 sexual partners (range: 1-25) per male in the previous 3 months. All examined N. gonorrhoeae isolates were susceptible to ceftriaxone (96/96), azithromycin (91/91), cefixime (91/91) and spectinomycin (91/91). For ciprofloxacin and gentamicin, respectively, 98.9% (91/92) and 91.3% (84/92) of the isolates were susceptible and 1.1% (1/92) and 8.7% (8/92) showed intermediate susceptibility/resistance. For tetracycline and benzylpenicillin, respectively, 38.0% (35/92) and 22.0% (20/91) of the isolates were susceptible, 52.2% (48/92) and 74.7% (68/91) showed intermediate susceptibility/resistance and 9.8% (9/92) and 3.3% (3/91) were resistant. Syndromic treatment was administered as follows: 93.1% received 250 mg of ceftriaxone intramuscularly plus 100 mg of doxycycline orally q12h for 1-2 weeks and 6.9% received 500 mg of ciprofloxacin orally plus 100 mg of doxycycline orally q12h for 1 week.

    CONCLUSIONS: Ceftriaxone (250 mg) remains appropriate for gonorrhoea treatment in the examined population of men in Kingston, Jamaica. Surveillance of N. gonorrhoeae AMR should be expanded in Jamaica and other Caribbean countries to guide evidence-based treatment guidelines.

  • 31.
    Chen, Shao-Chun
    et al.
    National Center for STD Control, Chinese Center for Disease Control and Prevention, and Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, and Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.
    Yin, Yue-Ping
    National Center for STD Control, Chinese Center for Disease Control and Prevention, and Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, and Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.
    Dai, Xiu-Qin
    National Center for STD Control, Chinese Center for Disease Control and Prevention, and Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, and Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.
    Unemo, Magnus
    Örebro University, School of Health Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Chen, Xiang-Sheng
    National Center for STD Control, Chinese Center for Disease Control and Prevention, and Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, and Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.
    First nationwide study regarding ceftriaxone resistance and molecular epidemiology of Neisseria gonorrhoeae in China2016In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 1, p. 92-99Article in journal (Refereed)
    Abstract [en]

    Objectives: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern worldwide. This is the first nationwide study, performed within the China Gonococcal Antimicrobial Susceptibility Programme (China-GASP), regarding AMR, including ceftriaxone genetic resistance determinants, and molecular epidemiology of gonococci in China.

    Methods: Gonococcal isolates (naEuroS=aEuroS1257) from consecutive patients were collected at 11 sentinel sites distributed across China during 2012-13. Susceptibility to ceftriaxone, spectinomycin, ciprofloxacin and tetracycline was determined using the agar dilution method. Ceftriaxone resistance determinants penA and penB were examined using sequencing. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed for molecular epidemiology.

    Results: Among isolates, 0.2% were resistant to spectinomycin, 4.4% to ceftriaxone, 42.9% to tetracyclines (high-level resistance) and 99.8% to ciprofloxacin. Among 890 sequenced isolates, 16 (1.8%) possessed a penA mosaic allele; 4 of these isolates belonged to the MDR internationally spread NG-MAST genogroup G1407 (first description in China). Non-mosaic penA alleles with an A501T mutation and an A102D alteration in porB1b were statistically associated with decreased susceptibility/resistance to ceftriaxone. NG-MAST G10339, G1424 and G1053 were associated with decreased susceptibility/resistance to ceftriaxone.

    Conclusions: In China, ceftriaxone and spectinomycin can continue to be recommended for gonorrhoea treatment, with the possible exception of Hainan and Sichuan provinces where ceftriaxone resistance exceeded 5% and AMR surveillance needs to be strengthened. Molecular approaches including genotyping and AMR determinant analysis can be valuable to supplement and enhance conventional surveillance of gonococcal AMR in China.

  • 32.
    Chen, Shao-Chun
    et al.
    China CDC, National Center STD Control, Nanjing, Peoples R China; Chinese Academy of Medical Science, Inst Dermatol, Nanjing, Peoples R China; Peking Union Med Coll, Nanjing, Peoples R China; Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Peoples R China.
    Yin, Yue-Ping
    China CDC, Natl Ctr STD Control, Nanjing, Peoples R China; Chinese Acad Med Sci, Inst Dermatol, Nanjing, Peoples R China;Peking Union Med Coll, Nanjing, Peoples R China; Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Peoples R China.
    Dai, Xiu-Qin
    China CDC, Natl Ctr STD Control, Nanjing, Peoples R China;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Peoples R China;Peking Union Med Coll, Nanjing, Peoples R China;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Peoples R China.
    Yu, Rui-Xing
    China CDC, Natl Ctr STD Control, Nanjing, Peoples R China;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Peoples R China;Peking Union Med Coll, Nanjing, Peoples R China;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Peoples R China.
    Han, Yan
    China CDC, Natl Ctr STD Control, Nanjing, Peoples R China;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Peoples R China;Peking Union Med Coll, Nanjing, Peoples R China;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Peoples R China.
    Sun, Hou-Hua
    China CDC, Natl Ctr STD Control, Nanjing, Peoples R China;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Peoples R China;Peking Union Med Coll, Nanjing, Peoples R China;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Peoples R China.
    Ohnishi, Makoto
    National Institute Infection Diseases (国立感染症研究所), Tokyo, Japan..
    Unemo, Magnus
    Örebro University Hospital. Dept Lab Med, WHO Collaborating Ctr Gonorrhoea & Other STIs, Örebro University Hospital, Örebro, Sweden.
    Chen, Xiang-Sheng
    China CDC, Natl Ctr STD Control, Nanjing, Peoples R China;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Peoples R China;Peking Union Med Coll, Nanjing, Peoples R China;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Peoples R China.
    Prevalence and Molecular Epidemiological Typing of Penicillinase-Producing Neisseria gonorrhoeae and Their bla(TEM-135) Gene Variants in Nanjing, China2013In: Sexually Transmitted Diseases, ISSN 0148-5717, E-ISSN 1537-4521, Vol. 40, no 11, p. 872-876Article in journal (Refereed)
    Abstract [en]

    Background: This study aimed to investigate the prevalence of penicillinase-producing Neisseria gonorrhoeae (PPNG) and their bla(TEM-135) gene variant in 2007 and 2012 in Nanjing, China. In addition, molecular epidemiological typing of all isolates was performed to elucidate the genetic relationships of the PPNG strains. Methods: A total of 199 and 77 N. gonorrhoeae isolates were collected at the National Center for STD Control in 2007 and 2012, respectively. Nitrocefin tests were performed to identify PPNG. Mismatch amplification mutation assay was used to identify bla(TEM-135). All isolates were genotyped using N. gonorrhoeae multiantigen sequence typing (NG-MAST), and additionally, porB-based phylogenetic analysis was performed for the PPNG isolates. Results: The total prevalence of PPNG isolates was 41% (114/276) and 58% (66/114) of these PPNG isolates possessed bla(TEM-135). In 2007, 45% (90/199) produced beta-lactamase, and of those PPNG, 58% (52/90) possessed bla(TEM-135). In 2012, 31% (24/77) were PPNG, and 58% (14/24) of those isolates contained bla(TEM-135). There were 162 NG-MAST STs among the 276 isolates, and 89 of those were novel STs. A strong association between specific NG-MAST STs and bla(TEM-135) was found, and the porB-based phylogenetic analysis showed a distant evolutionary relationship between isolates in 2007 and isolates in 2012. Conclusions: A high prevalence of PPNG and bla(TEM-135) was found in Nanjing, China. bla(TEM-135) might be a precursor in the evolution into an extended-spectrum beta-lactamase that can degrade ceftriaxone, which stresses the need to continuously monitor PPNG, bla(TEM-135), and additional evolving bla(TEM) gene variants.

  • 33.
    Chisholm, S. A.
    et al.
    Sexually Transmitted Bacteria Reference Lab, Health Protect Agency, London, England..
    Unemo, Magnus
    Natl Reference Lab Pathogen Neisseria, Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Quaye, N.
    Sexually Transmitted Bacteria Reference Lab, Health Protect Agency, London, England..
    Johansson, E.
    Natl Reference Lab Pathogen Neisseria, Dept Lab Med, Örebro Univ Hosp, Örebro, Sweden.
    Cole, M. J.
    Sexually Transmitted Bacteria Reference Lab, Health Protect Agency, London, England..
    Ison, C. A.
    Sexually Transmitted Bacteria Reference Lab, Health Protect Agency, London, England.
    Van de Laar, M. Jw
    European Center Disease Prevention & Control, Stockholm, Sweden.
    Molecular epidemiological typing within the European Gonococcal Antimicrobial Resistance Surveillance Programme reveals predominance of a multidrug-resistant clone2013In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 18, no 3, p. 14-23, article id 20358Article in journal (Refereed)
    Abstract [en]

    Treatment of gonorrhoea is threatened by antimicrobial resistance, and decreased susceptibility and resistance to recommended therapies is emerging in Europe. Current associations between resistance and molecular type remain poorly understood. Gonococcal isolates (n=1,066) collected for the 2009 and 2010 European Gonococcal Antimicrobial Surveillance Programme were typed by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). A total of 406 sequence types (STs) were identified, 125 of which occurred in >= two isolates. Seven major genogroups of closely related STs (varying by <= 1% at just one of the two target loci) were defined. Genogroup 1407 (G1407), observed in 20/21 countries and predominant in 13/21 countries, accounted for 23% of all isolates and was associated with decreased susceptibility to cefixime and resistance to ciprofloxacin and raised minimum inhibitory concentrations for ceftriaxone and azithromycin. Genogroup 225 (G225), associated with ciprofloxacin resistance, was observed in 10% of isolates from 19/21 countries. None of the other genogroups were associated with antimicrobial resistance. The predominance of a multidrug-resistant clone (G1407) in Europe is worrying given the recent reports of recommended third generation cephalosporins failing to treat infections with this clone. Identifying associations between ST and antimicrobial resistance aids the understanding of the dissemination of resistant clones within a population and could facilitate development of targeted intervention strategies.

  • 34.
    Clarke, E.
    et al.
    Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.
    Patel, C.
    Solihull Hospital, Solihull, UK.
    Patel, R.
    Department of Genitourinary Medicine, Southampton Medical School, University of Southampton, Southampton, UK; Solent NHS Trust, Southampton, UK.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Faculty of Medicine and Health, World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections.
    The 2018-19 International Union against Sexually Transmitted Infections European Collaborative Clinical Group report on the diagnosis and treatment of gonorrhoea in Europe2020In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 31, no 1, p. 77-81Article in journal (Refereed)
    Abstract [en]

    The European Collaborative Clinical Group (ECCG) has been surveying clinical management of sexually transmitted infections (STIs) in Europe since its inauguration in 2011. The ECCG is a network of nearly 130 STI specialists from 34 European countries who conduct questionnaire-based research across the European region. The research of ECCG focuses on providing data regarding clinical practice to inform European STI guideline development and revisions. The present paper describes the results of the 2018–19 ECCG survey regarding diagnosis and treatment of gonorrhoea in Europe.

  • 35.
    Clifton, Soazig
    et al.
    University College London, Institute for Global Health, London, UK.
    Field, Nigel
    University College London, Institute for Global Health, London, UK.
    Prior, Gillian
    University College London, Institute for Global Health, London, UK.
    Aldridge, Robert
    University College London, Institute for Health Informatics, London, UK.
    Bonell, Chris
    London School of Hygiene and Tropical Medicine, Faculty of Public Health and Policy, London, UK.
    Copas, Andrew
    University College London, Institute for Global Health, London, UK.
    Gibbs, Jo
    University College London, Institute for Global Health, London, UK.
    Macdowall, Wendy
    London School of Hygiene and Tropical Medicine, Faculty of Public Health and Policy, London, UK.
    Mitchell, Kirstin
    University of Glasgow, MRC/CSO Social and Public Health Sciences Unit, Glasgow, UK.
    Tanton, Clare
    London School of Hygiene and Tropical Medicine, Department of Infectious Disease Epidemiology, London, UK.
    Thomson, Nicholas
    Wellcome Trust Sanger Institute, Pathogen Genomics, Hinxton, UK.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Sonnenberg, Pam
    University College London, Centre for Population Research in Sexual Health and HIV, Institute for Global Health, London, UK.
    Mercer, Catherine
    University College London, Centre for Population Research in Sexual Health and HIV, Institute for Global Health, London, UK.
    WHAT IS THE OPTIMUM METHOD FOR COLLECTING ROBUST DATA TO UNDERSTAND A NATION'S SEXUAL HEALTH NEEDS?2019In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, no Suppl. 1, p. A181-A181Article in journal (Other academic)
  • 36.
    Cole, Michelle J.
    et al.
    UK Health Security Agency, London, United Kingdom.
    Day, Michaela
    UK Health Security Agency, London, United Kingdom.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and other STIs.
    Amato-Gauci, Andrew J.
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. University College London (UCL), London, United Kingdom; World Health Organization Collaborating Centre for Gonorrhoea and other STIs, Örebro University, Örebro, Sweden.
    The European response to control and manage multi- and extensively drug-resistant Neisseria gonorrhoeae2022In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 27, no 18, p. 37-43Article in journal (Refereed)
    Abstract [en]

    Because cefixime and ceftriaxone resistance in Neisseria gonorrhoeae and gonorrhoea treatment failures were increasing, a response plan to control and manage multidrug-resistant N. gonorrhoeae (MDR-NG) in Europe was published in 2012. The three main areas of the plan were to: (i) strengthen surveillance of antimicrobial resistance (AMR), (ii) implement monitoring of treatment failures and (iii) establish a communication strategy to increase awareness and disseminate AMR results. Since 2012, several additional extensively drug-resistant N. gonorrhoeae (XDR-NG) strains have emerged, and strains with high-level ceftriaxone resistance spread internationally. This prompted an evaluation and review of the 2012 European Centre for Disease Prevention and Control (ECDC) response plan, revealing an overall improvement in many aspects of monitoring AMR in N. gonorrhoeae; however, treatment failure monitoring was a weakness. Accordingly, the plan was updated in 2019 to further support European Union/European Economic Area (EU/EEA) countries in controlling and managing the threat of MDR/XDR-NG in Europe through further strengthening of AMR surveillance and clinical management including treatment failure monitoring. The plan will be assessed biennially to ensure its effectiveness and its value. Along with prevention, diagnostic, treatment and epidemiological surveillance strategies, AMR surveillance is essential for effective control of gonorrhoea.

  • 37.
    Cole, Michelle J.
    et al.
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
    Quaye, Nerteley
    National Mycobacterium Reference Service, National Infection Service, Public Health England, London, UK.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs.
    Day, Michaela
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
    Fagan, Elizabeth
    United Kingdom National External Quality Assessment Service (UK NEQAS), National Infection Service, Public Health England, London, UK.
    Ison, Catherine
    Sexually Transmitted Bacteria Reference Unit (retired), Public Health England, London, UK.
    Pitt, Rachel
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
    Seaton, Shila
    United Kingdom National External Quality Assessment Service (UK NEQAS), National Infection Service, Public Health England, London, UK.
    Woodford, Neil
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
    Stary, Angelika
    Outpatients` Centre for the Diagnosis of Infectious Venero-Dermatological Diseases, Vienna, Austria.
    Pleininger, Sonja
    National Reference Centre for Gonococci, Austrian Agency for Health and Food Safety, Vienna, Austria.
    Crucitti, Tania
    Institute of Tropical Medicine, Antwerp, Belgium.
    Hunjak, Blaženka
    Croatian Institute of Public Health, Zagreb, Croatia.
    Maikanti, Panayiota
    Microbiology Department, Nicosia General Hospital, Nicosia, Cyprus.
    Hoffmann, Steen
    Department for Bacteria, Parasites and Fungi Infectious Diseases Preparedness, Statens Serum Institut, Copenhagen, Denmark.
    Viktorova, Jelena
    Central Laboratory of Communicable Diseases, Tallinn, Estonia.
    Buder, Susanne
    Laboratory for Gonococci, Vivantes Klinikum, South, Berlin, Germany.
    Kohl, Peter
    Laboratory for Gonococci, Vivantes Klinikum, South, Berlin, Germany.
    Tzelepi, Eva
    National Reference Centre for N. gonorrhoeae, Laboratory of Bacteriology of the Hellenic Pasteur Institute, Athens, Greece.
    Siatravani, Eirini
    National Reference Centre for N. gonorrhoeae, Laboratory of Bacteriology of the Hellenic Pasteur Institute, Athens, Greece.
    Balla, Eszter
    Bacterial STI Reference Laboratory, National Public Health Institute, Budapest, Hungary.
    Hauksdóttir, Guðrún Svanborg
    Landspitali University Hospital, Reykjavik, Iceland.
    Rose, Lisa
    National Gonococcal Reference Laboratory, St James's Hospital, Dublin, Ireland.
    Stefanelli, Paola
    Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
    Carannante, Anna
    Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
    Pakarna, Gatis
    National Microbiology Reference Laboratory, Latvian Centre of Infectious Diseases, Riga East University Hospital, Riga, Latvia.
    Mifsud, Francesca
    Bacteriology Laboratory, Mater Dei Hospital, Msida, Malta.
    Cassar, Rosann Zammit
    Bacteriology Laboratory, Mater Dei Hospital, Msida, Malta.
    Linde, Ineke
    Streeklaboratorium/Bacteriologie, GGD Amsterdam, Amsterdam, The Netherlands.
    Bergheim, Thea
    Department of Medical Microbiology, Oslo University Hospital, Oslo, Norway.
    Steinbakk, Martin
    Norwegian Institute of Public Health, Oslo, Norway.
    Mlynarczyk-Bonikowska, Beata
    Department of Diagnostics of Sexually Transmitted Diseases, Medical University of Warsaw, Warsaw, Poland.
    Borrego, Maria-José
    Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal.
    Shepherd, Jill
    Scottish Bacterial Sexually Transmitted Infections Reference Laboratory, Royal Infirmary of Edinburgh, Edinburgh, UK.
    Pavlik, Peter
    Medirex a.s., Bratislava, Slovakia.
    Jeverica, Samo
    Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
    Vazquez, Julio
    Reference Laboratory for Neisseria National Centre for Microbiology - Instituto de Salud Carlos III, Majadahonda, Spain.
    Abad, Raquel
    Reference Laboratory for Neisseria National Centre for Microbiology - Instituto de Salud Carlos III, Majadahonda, Spain.
    Weiss, Sabrina
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK; Institute of Virology, Charite - Universitätsmedizin Berlin, Berlin, Germany; European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs.
    Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data2019In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 19, no 1, article id 281Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated.

    METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility.

    RESULTS: dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods.

    CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.

  • 38.
    Cole, Michelle J.
    et al.
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
    Quinten, Chantal
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Jacobsson, Susanne
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Day, Michaela
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
    Amato-Gauci, Andrew J.
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Woodford, Neil
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    The European gonococcal antimicrobial surveillance programme (Euro-GASP) appropriately reflects the antimicrobial resistance situation for Neisseria gonorrhoeae in the European Union/European Economic Area2019In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 19, no 1, article id 1040Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) antimicrobial resistance (AMR) data are used to inform gonorrhoea treatment guidelines; therefore the data need to be robust and representative. We assessed the extent to which Euro-GASP reflects national measures of the AMR situation for Neisseria gonorrhoeae across the European Union/European Economic Area (EU/EEA).

    METHODS: We compared data from Euro-GASP with published national gonococcal AMR data from 15 countries for azithromycin, cefixime and ciprofloxacin for the period 2009 to 2013 and performed Poisson regression to identify differences (p < 0.05) between the proportions of resistant isolates. The 2014 Euro-GASP AMR data for each country (n = 19) were weighted to account for differences in the distribution of patient characteristics between Euro-GASP and EU/EEA epidemiological gonorrhoea surveillance data. Data were compared to determine whether estimates of resistance levels differed with regards to the 5% threshold used to assess the clinical utility of first-line gonorrhoea treatments. We assessed the quality of decentralised testing by comparing AMR data for isolates tested both centrally and in the participating laboratories, and by evaluating external quality assessment (EQA) performance.

    RESULTS: There was no significant difference for azithromycin, cefixime and ciprofloxacin resistance when Euro-GASP country data were compared with data from national reports. Weighting slightly altered the Euro-GASP AMR estimates (by between - 4.7 and 4.7% from the unweighted estimates). Weighting resulted in greater changes in estimates of resistance to azithromycin (from - 9.5 to 2.7%) and ciprofloxacin (from - 14.8 to 17.9%) in countries with low isolate numbers and low completeness of reporting (n = 3). Weighting caused AMR levels to fall below or above the 5% threshold for cefixime or azithromycin, respectively in only two countries. Susceptibility category data submitted from the decentralised Euro-GASP laboratories were concordant with the Euro-GASP data (> 90%). EQA performance was also good; < 5% of the minimum inhibitory concentration (MIC) results differed by > 4-fold from the modal MIC of the EQA isolate.

    CONCLUSIONS: The overall prevalence of AMR reported by Euro-GASP reflects closely the AMR situation for N. gonorrhoeae in the EU/EEA. Euro-GASP data can be used to provide robust AMR estimates to inform the European guideline for the management of gonorrhoea.

  • 39.
    Cole, Michelle J.
    et al.
    Public Health England, Sexually Transmitted Bacteria Reference Unit, Microbiological Services, London, England, United Kingdom.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Pitt, Rachel
    Public Health England, Sexually Transmitted Bacteria Reference Unit, Microbiological Services, London, England, United Kingdom.
    Grigorjev, Vlad
    Public Health England, Sexually Transmitted Bacteria Reference Unit, Microbiological Services, London, England, United Kingdom.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe?: Results from the 2013 European surveillance2015In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 15, article id 321Article in journal (Refereed)
    Abstract [en]

    Background: The emerging resistance to the extended-spectrum cephalosporins (ESCs) in Neisseria gonorrhoeae together with increasing incidence of gonorrhoea cases in many countries have been global public health concerns. However, in recent years the levels of ESC resistance have decreased in several regions worldwide. We describe the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) data from 2013, and compare them to corresponding data from 2009-2012.

    Methods: During 2013, N. gonorrhoeae isolates from 21 participating countries were examined. Antimicrobial susceptibility testing (Etest or agar dilution) was performed for cefixime, ceftriaxone, ciprofloxacin, azithromycin, spectinomycin and gentamicin. Statistical analyses were performed to identify significant changes in resistance between years and to investigate associations between patients with resistant gonococcal isolates and collected epidemiological variables.

    Results: In total, 93 (4.7 %) of 1994 isolates displayed resistance to cefixime, representing an increase compared to the 3.9 % detected in 2012 (p = 0.23). Cefixime resistance was detected in 13 (61.9 %) of the 21 countries. Cefixime resistance among men who have sex with men was only 1.2 %, compared to 5.6 % and 6.1 % in females and male heterosexuals, respectively. The univariate analysis confirmed that isolates resistant to cefixime were more likely to be from females (OR 4.87, p < 0.01) or male heterosexuals (OR 5.32, p < 0.01). Seven (0.4 %) isolates displayed ceftriaxone resistance (in addition to cefixime resistance) compared to three and 10 isolates in 2012 and 2011, respectively. All 93 isolates with cefixime resistance were additionally resistant to ciprofloxacin and 16 (17.2 %) were also resistant to azithromycin. Among all tested isolates (n = 1994), the ciprofloxacin resistance level (52.9 %) was higher than in 2012 (50.1 %; p = 0.08), and azithromycin resistance (5.4 %) increased since 2012 (4.5 %; p = 0.16).

    Conclusions: In 2013, the ESC resistance was again slightly increasing in Europe. This emphasises the importance of implementing the actions outlined in the European and additional response plans, particularly activities strengthening the surveillance of antimicrobial resistance. Ceftriaxone combined with azithromycin remains a satisfactory option for the first-line treatment of gonorrhoea. However novel antimicrobials (new derivatives of previously developed antimicrobials or newly developed antimicrobials) for effective monotherapy or at least inclusion in new dual antimicrobial therapy regimens (combined with previously developed antimicrobials or novel antimicrobials) will likely be required.

  • 40.
    Cole, Michelle J.
    et al.
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, London, United Kingdom.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, Örebro University Hospital, Örebro, Sweden.
    Woodford, Neil
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, London, United Kingdom.
    Tripodo, Francesco
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, London, United Kingdom.
    Amato-Gauci, Andrew J.
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and other STIs, Örebro University Hospital, Örebro, Sweden.
    Overall Low Extended-Spectrum Cephalosporin Resistance but high Azithromycin Resistance in Neisseria gonorrhoeae in 24 European Countries, 20152017In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 17, article id 617Article in journal (Refereed)
    Abstract [en]

    Background: Surveillance of Neisseria gonorrhoeae antimicrobial susceptibility in Europe is performed through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), which additionally provides data to inform the European gonorrhoea treatment guideline; currently recommending ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. We present antimicrobial susceptibility data from 24 European countries in 2015, linked to epidemiological data of patients, and compare the results to Euro-GASP data from previous years.

    Methods: Antimicrobial susceptibility testing by MIC gradient strips or agar dilution methodology was performed on 2134 N. gonorrhoeae isolates and interpreted using EUCAST breakpoints. Patient variables associated with resistance were established using logistic regression to estimate odds ratios (ORs).

    Results: In 2015, 1.7% of isolates were cefixime resistant compared to 2.0% in 2014. Ceftriaxone resistance was detected in only one (0.05%) isolate in 2015, compared with five (0.2%) in 2014. Azithromycin resistance was detected in 7.1% of isolates in 2015 (7.9% in 2014), and five (0.2%) isolates displayed high-level azithromycin resistance (MIC = 256 mg/L) compared with one (0.05%) in 2014. Ciprofloxacin resistance remained high (49.4%, vs. 50.7% in 2014). Cefixime resistance significantly increased among heterosexual males (4.1% vs. 1.7% in 2014), which was mainly attributable to data from two countries with high cefixime resistance (similar to 11%), however rates among men-who-have-sex-with-men (MSM) and females continued to decline to 0.5% and 1%, respectively. Azithromycin resistance in MSM and heterosexual males was higher (both 8.1%) than in females (4.9% vs. 2.2% in 2014). The association between azithromycin resistance and previous gonorrhoea infection, observed in 2014, continued in 2015 (OR 2.1, CI 1.2-3.5, p < 0.01).

    Conclusions: The 2015 Euro-GASP sentinel system revealed high, but stable azithromycin resistance and low overall resistance to ceftriaxone and cefixime. The low cephalosporin resistance may be attributable to the effectiveness of the currently recommended first-line dual antimicrobial therapy; however the high azithromycin resistance threatens the effectiveness of this therapeutic regimen. Whether the global use of azithromycin in mono-or dual antimicrobial therapy of gonorrhoea is contributing to the global increases in azithromycin resistance remains to be elucidated. The increasing cefixime resistance in heterosexual males also needs close monitoring.

  • 41.
    Cole, Michelle J.
    et al.
    Sexually Transmitted Bacteria Reference Unit, Public Health England, London, UK.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Grigorjev, Vlad
    Sexually Transmitted Bacteria Reference Unit, Public Health England, London, UK.
    Quaye, Nerteley
    National Mycobacterium Reference Laboratory, Public Health England, London, UK.
    Woodford, Neil
    Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, London, UK.
    Genetic diversity of bla(TEM) alleles, antimicrobial susceptibility and molecular epidemiological characteristics of penicillinase-producing Neisseria gonorrhoeae from England and Wales2015In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 70, no 12, p. 3238-3243Article in journal (Refereed)
    Abstract [en]

    Objectives: The objective of this study was to investigate the genetic diversity of bla(TEM) alleles, antimicrobial susceptibility and molecular epidemiological characteristics of penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates collected in 2012 from England and Wales.

    Methods: PPNG isolates were from the 2012 Gonococcal Resistance to Antimicrobial Surveillance Programme (GRASP). Their susceptibility to seven antimicrobials was determined using agar dilution methodology. beta-Lactamase production was detected using a nitrocefin test. beta-Lactamase plasmid types were determined and bla(TEM) genes were sequenced. Isolates were also typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST).

    Results: Seventy-three PPNG isolates were identified in the 2012 GRASP collection (4.6%, 73/1603). Three different bla(TEM) alleles were identified, encoding three TEM amino acid sequences: TEM-1 (53%), TEM-1 with a P14S substitution (19%) and TEM-135 (27%). The bla(TEM-135) allele was present in nine different NG-MAST types and was found mostly on Asian (60%) and Toronto/Rio (35%) plasmids. By contrast, most TEM-1-encoding plasmids were African (98%). All the TEM-135 isolates displayed high-level ciprofloxacin and tetracycline resistance.

    Conclusions: The high proportion of bla(TEM-135) alleles (27%) demonstrates that this variant is circulating within several gonococcal lineages. Only a single specific mutation near the beta-lactamase active site could result in TEM-135 evolving into an ESBL. This is concerning particularly because the TEM-135 isolates were associated with high-level ciprofloxacin and tetracycline resistance. It is encouraging that no further TEM alleles were detected in this gonococcal population; however, vigilance is vital as an ESBL in N. gonorrhoeae would render the last remaining option for monotherapy, ceftriaxone, useless.

  • 42.
    Cole, Michelle Jayne
    et al.
    National Infection Service, Public Health England, London, UK.
    Davis, Grahame S.
    National Infection Service, Public Health England, London, UK.
    Fifer, Helen
    National Infection Service, Public Health England, London, UK.
    Saunders, John Michael
    National Infection Service, Public Health England, London, UK; Research Department of Infection and Population Health, University College London, London, UK.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology.
    Hadad, Ronza
    Örebro University, School of Medical Sciences.
    Roberts, David J.
    National Infection Service, Public Health England, London, UK.
    Fazal, Mohammed
    National Infection Service, Public Health England, London, UK.
    Day, Michaela Joanne
    National Infection Service, Public Health England, London, UK.
    Minshull, Jack
    National Infection Service, Public Health England, London, UK.
    Muir, Peter
    Bristol Public Health Laboratory, Public Health England, Bristol, UK.
    Horner, Paddy J.
    School of Social and Community Medicine, University of Bristol, Bristol, UK; Bristol Sexual Health Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
    Gill, Noel O.
    National Infection Service, Public Health England, London, UK.
    Folkard, Kate
    National Infection Service, Public Health England, London, UK.
    No widespread dissemination of Chlamydia trachomatis diagnostic: escape variants and the impact of Neisseria gonorrhoeae positivity on the Aptima Combo 2 assay2022In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 98, no 5, p. 366-370Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: (NG) with the Hologic Aptima CT (ACT) assay was recommended to identify any CT variants.

    METHODS: From June to October 2019, specimens with discrepant AC2/ACT CT results were submitted to Public Health England and screened for detectable CT DNA using an inhouse real-time (RT)-PCR. When enough DNA was present, partial CT 23S rRNA gene sequencing was performed. Analysis of available relative light units and interpretative data was performed.

    RESULTS: A total of 317 discordant AC2/ACT specimens were collected from 315 patients. Three hundred were tested on the RT-PCR; 53.3% (n=160) were negative and 46.7% (n=140) were positive. Due to low DNA load in most specimens, sequencing was successful for only 36 specimens. The CT 23S rRNA wild-type sequence was present in 32 specimens, and two variants with C1514T or G1523A mutation were detected in four specimens from three patients. Of the discordant specimens with NG interpretation, 36.6% of NG-negative/CT-negative AC2 specimens had detectable CT DNA on the inhouse RT-PCR vs 53.3% of NG-positive/CT-negative specimens.

    CONCLUSIONS: No widespread dissemination of AC2 diagnostic-escape CT variants has occurred in England. We however identified the impact of NG positivity on the discordant AC2/ACT specimens; a proportion appeared due to NG positivity and the associated NG signal, rather than any diagnostic-escape variants or low DNA load. Several patients with gonorrhoea may therefore receive false-negative AC2 CT results. Single diagnostic targets and multiplex diagnostic assays have their limitations such as providing selection pressure for escape mutants and potentially reduced sensitivity, respectively. These limitations must be considered when establishing diagnostic pathways.

  • 43.
    Connolly, Kristie L.
    et al.
    Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, United States.
    Eakin, Ann E.
    Division of Microbiology and Infectious Diseases, National Institutes of Health, Rockville, MD, United States.
    Gomez, Carolina
    Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, United States.
    Osborn, Blaire L.
    Division of Microbiology and Infectious Diseases, National Institutes of Health, Rockville, MD, United States.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology.
    Jerse, Ann E.
    Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, United States .
    Pharmacokinetic Data Are Predictive of In Vivo Efficacy for Cefixime and Ceftriaxone against Susceptible and Resistant Neisseria gonorrhoeae Strains in the Gonorrhea Mouse Model2019In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 63, no 3, article id e01644-18Article in journal (Refereed)
    Abstract [en]

    There is a pressing need for drug development for gonorrhea. Here we describe pharmacokinetics/pharmacodynamics (PK/PD) analysis of extended-spectrum cephalosporins (ESC) against drug-susceptible and drug-resistant gonococcal strains in a murine genital tract infection model. PK determined in uninfected mice displayed a clear dose response in plasma levels following single doses of ceftriaxone (CRO) (intraperitoneal) or cefixime (CFM) (oral). The observed doses required for efficacy against ESCS strain FA1090 were 5 mg/kg (CRO) and 12 mg/kg (CFM); these doses had estimated therapeutic times (time of free drug above the MIC, fTMIC) of 24 h and 37 h, respectively. No single dose of CRO or CFM was effective against the ESCR strain H041. However, fractionation (TIDq8h) of a 120 mg/kg dose of CRO resulted in estimated therapeutic times in the range of 23 h and cleared H041 infection in a majority (90%) of mice, comparable to gentamicin. In contrast, multiple CFM doses of 120 or 300 mg/kg administered TIDq8h cleared infection in ≤ 50% of mice with therapeutic times estimated from single-dose PK data, of 13 and 27 h, respectively. This study reveals a clear relationship between plasma ESC levels and bacterial clearance rates in the gonorrhea mouse model. The PK/PD relationships in mice reflected that observed in humans with in vivo efficacy against an ESCS strain requiring doses that yielded an fTMIC in excess of 20-24 h. PK data also accurately predicted the failure of single doses of ESCs against an ESCR strain and were useful in designing effective dosing regimens.

  • 44.
    Dahlberg, Jenny
    et al.
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Hadad, Ronza
    Örebro University, School of Science and Technology. WHO Collaborating Centre for Gonorrhoea and other STIs, Örebro University Hospital, Örebro, Sweden.
    Elfving, Karin
    Department of Clinical Microbiology, Falu Lasarett, Falun, Sweden.
    Larsson, Inger
    Department of Clinical Microbiology, Sunderby Hospital, Luleå, Sweden.
    Isaksson, Jenny
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Magnuson, Anders
    Fredlund, Hans
    WHO Collaborating Centre for Gonorrhoea and other STIs, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and other STIs, Örebro University Hospital, Örebro, Sweden.
    Herrmann, Bjőrn
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Ten years transmission of the new variant of Chlamydia trachomatis in Sweden: prevalence of infections and associated complications2018In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 94, no 2, p. 100-104Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: In 2006, a new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden. It has a deletion in the plasmid resulting in failed detection by the single target systems from Abbott and Roche used at that time, whereas the third system used, from Becton Dickinson (BD), detects nvCT. The proportion of nvCT was initially up to 65% in counties using Abbott/Roche systems. This study analysed the proportion of nvCT from 2007 to 2015 in four selected counties and its impact on chlamydia-associated complications.

    METHODS: C. trachomatis-positive specimens collected from 2007 to 2015 were analysed by a specific PCR to identify nvCT cases. Genotyping was performed by multilocus sequence typing (MLST) and ompA sequencing. Ectopic pregnancy and pelvic inflammatory disease records were extracted from the national registers.

    RESULTS: In total, 5101 C. trachomatis-positive samples were analysed. The nvCT proportion significantly decreased in the two counties using Roche systems, from 56% in 2007 to 6.5% in 2015 (p<0.001). In the two counties using BD systems, a decrease was also seen, from 19% in 2007 to 5.2% in 2015 (p<0.001). Fifteen nvCT cases from 2015 and 102 cases from 2006 to 2009 had identical MLST profiles. Counties using Roche/Abbott systems showed higher mean rates of ectopic pregnancy and pelvic inflammatory disease compared with counties using BD systems.

    CONCLUSIONS: The nvCT proportion has decreased in all counties and converged to a low prevalence irrespective of previous rates. Genotyping showed that nvCT is clonal and genetically stable. Failing detection only marginally affected complication rates.

  • 45.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden .
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Rider, Jennifer R.
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Erratum to: Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer2016In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, article id 36Article in journal (Refereed)
  • 46.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Rider, Jennifer R.
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden; Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden .
    Andersson, Swen-Olof
    Örebro University, School of Health Sciences. Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer2016In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, article id 26Article in journal (Refereed)
    Abstract [en]

    Background: Prostate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.

    Methods: We included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient's prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.

    Results: The results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93-11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.

    Conclusion: The present study provides further evidence for a role of P. acnes in prostate cancer development.

  • 47.
    Davidsson, Sabina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Mölling, Paula
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rider, Jennifer R.
    Karlsson, Mats G.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Elgh, Fredrik
    Andrén, Ove
    Örebro University, School of Medicine, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden.
    Prevalence and typing of Propionibacterium acnes in prostate tissue obtained from men with prostate cancer and from health controlsManuscript (preprint) (Other academic)
  • 48.
    Davidsson, Sabina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Elgh, Fredrik
    Örebro University, School of Health and Medical Sciences. Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Olsson, Jan
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Multilocus sequence typing and repetitive-sequence-based PCR (DiversiLab) for molecular epidemiological characterization of Propionibacterium acnes isolates of heterogeneous origin2012In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 18, no 4, p. 392-399Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes is a gram-positive bacillus predominantly found on the skin. Although it is considered an opportunistic pathogen it is also been associated with severe infections. Some specific P. acnes subtypes are hypothesized to be more prone to cause infection than others. Thus, the aim of the present study was to investigate the ability to discriminate between P. acnes isolates of a refined multilocus sequence typing (MLST) method and a genotyping method, DiversiLab, based on repetitive-sequence-PCR technology.

    The MLST and DiversiLab analysis were performed on 29 P. acnes isolates of diverse origins; orthopedic implant infections, deep infections following cardiothoracic surgery, skin, and isolates from perioperative tissue samples from prostate cancer. Subtyping was based on recA, tly, and Tc12S sequences.

    The MLST analysis identified 23 sequence types and displayed a superior ability to discriminate P. acnes isolates compared to DiversiLab and the subtyping. The highest discriminatory index was found when using seven genes. DiversiLab was better able to differentiate the isolates compared to the MLST clonal complexes of sequence types.

    Our results suggest that DiversiLab can be useful as a rapid typing tool for initial discrimination of P. acnes isolates. When better discrimination is required, such as for investigations of the heterogeneity of P. acnes isolates and its involvement in different pathogenic processes, the present MLST protocol is valuable.

  • 49.
    Day, Michaela
    et al.
    Public Health England, National Infection Service, London, UK.
    Cole, Michelle
    Public Health England, National Infection Service, London, UK.
    Spiteri, Gianfranco
    ECDC, Stockholm, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Woodford, Neil
    Public Health England, National Infection Service, London, UK.
    Amato-Gauci, Andrew
    ECDC, Stockholm, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    THE EUROPEAN GONOCOCCAL ANTIMICROBIAL SURVEILLANCE PROGRAMME FINDINGS 20172019In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, no Suppl. 1, p. A43-A43Article in journal (Other academic)
    Abstract [en]

    Background: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) annually investigates antimicrobial susceptibility data for Neisseria gonorrhoeae with patient epidemiological data to monitor current and emerging trends in antimicrobial resistance (AMR) across Europe. Susceptibility to ceftriaxone and azithromycin, currently recommended for combination treatment in the European management guideline, has decreased in the past; regular surveillance of AMR is cru-cial. We present the main Euro-GASP findings from 2017.

    Methods: Agar dilution and minimum inhibitory concentration (MIC) gradient strip tests were used to determine the antimicrobial susceptibility to cefixime, ceftriaxone and azithromycin (using EUCAST breakpoints) of 3248 N. gonorrhoeae isolates collected in 2017 from 27 countries across the European Union/European Economic Area (EU/EEA). Significance of changes in resistance compared to 2016 was analysed using Z-tests.

    Results: There were no isolates with ceftriaxone resistance (MIC>0.125 mg/L) (zero in 2016), 7.5% of isolates were azithromycin resistant (MIC>0.5 mg/L) (7.5% in 2016; p=0.93) and cefixime resistance (MIC>0.125 mg/L) was observed in 1.9% of isolates (2.1% in 2016; p=0.53). Seven isolates from four countries displayed high-level azithromycin resistance (MIC256 mg/L), which is the same number as observed in 2016, although in different countries (five countries in 2016). Ceftriaxone MICs for 28 isolates (0.9%) were 0.125 mg/L (on the resistance breakpoint) which is double the number observed in 2016 (14 isolates, 0.5%) although this increase is not statistically significant (p=0.33). Of the 28 isolates on the ceftriaxone resistance breakpoint, four showed intermediate susceptibility to azithromycin.

    Conclusion: Ceftriaxone, azithromycin and cefixime resistance levels remained stable compared with 2016. However, the current azithromycin resistance rate of 7.5% and the number of isolates on the resistance breakpoint for ceftriaxone threaten the effectiveness of the currently recommended European therapeutic regimen of ceftriaxone 500 mg plus azithromycin 2 g. Continued surveillance is essential together with, ultimately, development of new effective antimicrobials.

  • 50.
    Day, Michaela J.
    et al.
    UK Health Security Agency, London, UK.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Kulishev, Carina
    UK Health Security Agency, London, UK.
    Sajedi, Noshin
    UK Health Security Agency, London, UK.
    Woodford, Neil
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Blumel, Benjamin
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    van der Werf, Marieke J.
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Amato-Gauci, Andrew J.
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University, Örebro, Sweden; University College London (UCL), London, UK .
    Cole, Michelle J.
    UK Health Security Agency, London, UK.
    Significant increase in azithromycin "resistance" and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 20192022In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 22, no 1, article id 524Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2019 (26 countries), linked to patient epidemiological data, and compared with data from previous years.

    METHODS: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST clinical breakpoints, where available) of 3239 N. gonorrhoeae isolates from 26 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-test and the Pearson's χ2 test was used to assess significance of odds ratios for associations between patient epidemiological data and antimicrobial resistance.

    RESULTS: European N. gonorrhoeae isolates collected between 2016 and 2019 displayed shifting MIC distributions for; ceftriaxone, with highly susceptible isolates increasing over time and occasional resistant isolates each year; cefixime, with highly-susceptible isolates becoming increasingly common; azithromycin, with a shift away from lower MICs towards higher MICs above the EUCAST epidemiological cut-off (ECOFF); and ciprofloxacin which is displaying a similar shift in MICs as observed for azithromycin. In 2019, two isolates displayed ceftriaxone resistance, but both isolates had MICs below the azithromycin ECOFF. Cefixime resistance (0.8%) was associated with patient sex, with resistance higher in females compared with male heterosexuals and men-who-have-sex-with-men (MSM). The number of countries reporting isolates with azithromycin MICs above the ECOFF increased from 76.9% (20/26) in 2016 to 92.3% (24/26) in 2019. Isolates with azithromycin MICs above the ECOFF (9.0%) were associated with pharyngeal infection sites. Following multivariable analysis, ciprofloxacin resistance remained associated with isolates from MSM and heterosexual males compared with females, the absence of a concurrent chlamydial infection, pharyngeal infection sites and patients ≥ 25 years of age.

    CONCLUSIONS: Resistance to ceftriaxone and cefixime remained uncommon in EU/EEA countries in 2019 with a significant decrease in cefixime resistance observed between 2016 and 2019. The significant increase in azithromycin "resistance" (azithromycin MICs above the ECOFF) threatens the effectiveness of the dual therapy (ceftriaxone + azithromycin), i.e., for ceftriaxone-resistant cases, currently recommended in many countries internationally and requires close monitoring.

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