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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
    Region Örebro län.
    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 Array2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, artikel-id UNSP e76696Artikel i tidskrift (Refereegranskat)
    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 medicines2017Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, nr 7, artikel-id e1002366Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 3. 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 universitet, Institutionen för klinisk medicin.
    Danielsson, Dan
    Teneberg, Susann
    Lee, Woo-Kon
    Berg, Douglas E.
    Borén, Thomas
    Helicobacter pylori adhesion to carbohydrates2006Ingår i: Methods in Enzymology, ISSN 0076-6879, E-ISSN 1557-7988, Vol. 417, s. 293-339Artikel i tidskrift (Refereegranskat)
    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.

  • 4.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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, 2012-20152019Ingår i: PLoS ONE, E-ISSN 1932-6203, Vol. 14, nr 10, artikel-id e0223598Artikel i tidskrift (Refereegranskat)
    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.

  • 5.
    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 universitet, Institutionen för hälsovetenskaper. 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 gonorrhoeae2016Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, nr 7, s. 1856-1859Artikel i tidskrift (Refereegranskat)
    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.

  • 6.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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, 2015-162018Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, nr 7, s. 1854-1861Artikel i tidskrift (Refereegranskat)
    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.

  • 7.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 infections2019Ingår i: JCI Insight, ISSN 2379-3708, Vol. 4, nr 23, artikel-id 131886Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 INFECTIONS2019Ingår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 114, s. 470-470Artikel i tidskrift (Övrigt vetenskapligt)
  • 9.
    Bignell, C.
    et al.
    City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
    Unemo, Magnus
    Region Örebro län. 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]2014Ingår i: Przegląd Dermatologiczny, ISSN 0033-2526, Vol. 101, nr 2, s. 168-178Artikel i tidskrift (Refereegranskat)
  • 10.
    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 adults2013Ingår i: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 24, nr 2, s. 85-92Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    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 universitet, Institutionen för medicinska vetenskaper. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Jacobsson, Susanne
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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, 2013-20182020Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Boiko I, Golparian D, Jacobsson S, Krynytska I, Frankenberg A, Shevchenko T, Unemo M. Genomic epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates from Ukraine, 2013-2018 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.

  • 12.
    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 universitet, Institutionen för medicinska vetenskaper. 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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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, Ukraine2019Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, nr 9, s. 627-634Artikel i tidskrift (Refereegranskat)
    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.

  • 13.
    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 universitet, Institutionen för medicinska vetenskaper. 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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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, 2013-20182019Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, nr 7, s. 503-509Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    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 universitet, Institutionen för medicinska vetenskaper. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 study2019Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, nr 2, s. 129-132Artikel i tidskrift (Refereegranskat)
    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.

  • 15.
    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
    Region Örebro län. 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 adherence2017Ingår i: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, nr 3, s. 376-389, artikel-id S1931-3128(17)30075-6Artikel i tidskrift (Refereegranskat)
    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.

  • 16.
    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 universitet, Institutionen för hälsovetenskaper. 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 China2016Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, nr 1, s. 92-99Artikel i tidskrift (Refereegranskat)
    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.

  • 17.
    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
    Region Örebro län. 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, China2013Ingår i: Sexually Transmitted Diseases, ISSN 0148-5717, E-ISSN 1537-4521, Vol. 40, nr 11, s. 872-876Artikel i tidskrift (Refereegranskat)
    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.

  • 18.
    Chisholm, S. A.
    et al.
    Sexually Transmitted Bacteria Reference Lab, Health Protect Agency, London, England..
    Unemo, Magnus
    Region Örebro län. 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 clone2013Ingår i: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 18, nr 3, s. 14-23, artikel-id 20358Artikel i tidskrift (Refereegranskat)
    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.

  • 19.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 Europe2020Ingår i: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 31, nr 1, s. 77-81Artikel i tidskrift (Refereegranskat)
    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.

  • 20.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    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?2019Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, nr Suppl. 1, s. A181-A181Artikel i tidskrift (Övrigt vetenskapligt)
  • 21.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 data2019Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 19, nr 1, artikel-id 281Artikel i tidskrift (Refereegranskat)
    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.

  • 22.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 Area2019Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 19, nr 1, artikel-id 1040Artikel i tidskrift (Refereegranskat)
    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.

  • 23.
    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 universitet, Institutionen för hälsovetenskap och medicin.
    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 universitet, Institutionen för hälsovetenskap och medicin.
    Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe?: Results from the 2013 European surveillance2015Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, artikel-id 321Artikel i tidskrift (Refereegranskat)
    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.

  • 24.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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, 20152017Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 17, artikel-id 617Artikel i tidskrift (Refereegranskat)
    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.

  • 25.
    Cole, Michelle J.
    et al.
    Sexually Transmitted Bacteria Reference Unit, Public Health England, London, UK.
    Unemo, Magnus
    Örebro universitet, Institutionen för hälsovetenskap och medicin. 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 Wales2015Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 70, nr 12, s. 3238-3243Artikel i tidskrift (Refereegranskat)
    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.

  • 26.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. 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 Model2019Ingår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 63, nr 3, artikel-id e01644-18Artikel i tidskrift (Refereegranskat)
    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.

  • 27.
    Dahlberg, Jenny
    et al.
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Hadad, Ronza
    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 complications2018Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 94, nr 2, s. 100-104Artikel i tidskrift (Refereegranskat)
    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.

  • 28.
    Davidsson, Sabina
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. 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 universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Andersson, Swen-Olof
    Örebro universitet, Institutionen för hälsovetenskaper. 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 universitet, Institutionen för medicinska vetenskaper.
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. 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 cancer2016Ingår i: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, artikel-id 36Artikel i tidskrift (Refereegranskat)
  • 29.
    Davidsson, Sabina
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. 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 universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden; Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Carlsson, Jessica
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology, Örebro University Hospital, Örebro, Sweden .
    Andersson, Swen-Olof
    Örebro universitet, Institutionen för hälsovetenskaper. 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 universitet, Institutionen för medicinska vetenskaper.
    Andrén, Ove
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer2016Ingår i: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, artikel-id 26Artikel i tidskrift (Refereegranskat)
    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.

  • 30.
    Davidsson, Sabina
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Mölling, Paula
    Unemo, Magnus
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Rider, Jennifer R.
    Karlsson, Mats G.
    Andersson, Swen-Olof
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Elgh, Fredrik
    Andrén, Ove
    Örebro universitet, Institutionen för läkarutbildning.
    Söderquist, Bo
    Örebro universitet, Institutionen för läkarutbildning.
    Prevalence and typing of Propionibacterium acnes in prostate tissue obtained from men with prostate cancer and from health controlsManuskript (preprint) (Övrigt vetenskapligt)
  • 31.
    Davidsson, Sabina
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro universitet, Institutionen för läkarutbildning. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Elgh, Fredrik
    Örebro universitet, Hälsoakademin. Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Olsson, Jan
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Andrén, Ove
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro universitet, Institutionen för hälsovetenskap och medicin. 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 origin2012Ingår i: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 18, nr 4, s. 392-399Artikel i tidskrift (Refereegranskat)
    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.

  • 32.
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Woodford, Neil
    Public Health England, National Infection Service, London, UK.
    Amato-Gauci, Andrew
    ECDC, Stockholm, Sweden.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    THE EUROPEAN GONOCOCCAL ANTIMICROBIAL SURVEILLANCE PROGRAMME FINDINGS 20172019Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, nr Suppl. 1, s. A43-A43Artikel i tidskrift (Övrigt vetenskapligt)
    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.

  • 33.
    Day, Michaela J.
    et al.
    National Infection Service, Public Health England, London, UK.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Jacobsson, Susanne
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhea and other STIs.
    Woodford, Neil
    National Infection Service, Public Health England, London, UK.
    Amato-Gauci, Andrew J.
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Cole, Michelle J.
    National Infection Service, Public Health England, London, UK.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhea and other STIs.
    Euro-GASP, network
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 20162018Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 18, nr 1, artikel-id 609Artikel i tidskrift (Refereegranskat)
    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 2016 (25 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 breakpoints) of 2660 N. gonorrhoeae isolates from 25 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-tests.

    RESULTS: No isolates with resistance to ceftriaxone (MIC > 0.125 mg/L) were detected in 2016 (one in 2015). However, the proportion of isolates with decreased susceptibility to ceftriaxone (MICs from 0.03 mg/L to 0.125 mg/L) increased significantly (p = 0.01) from 2015 to 2016. There were 14 (0.5%) isolates with ceftriaxone MICs 0.125 mg/L (on the resistance breakpoint), of which one isolate was resistant to azithromycin and four showed intermediate susceptibility to azithromycin. Cefixime resistance was detected in 2.1% of isolates in 2016 compared with 1.7% in 2015 (p = 0.26) and azithromycin resistance in 7.5% in 2016 compared with 7.1% in 2015 (p = 0.74). Seven (0.3%) isolates from five countries displayed high-level azithromycin resistance (MIC≥256 mg/L) in 2016 compared with five (0.2%) isolates in 2015. Resistance rate to ciprofloxacin was 46.5% compared with 49.4% in 2015 (p = 0.06). No isolates were resistant to spectinomycin and the MICs of gentamicin remained stable compared with previous years.

    CONCLUSIONS: Overall AMR rates in gonococci in EU/EEA remained stable from 2015 to 2016. However, the ceftriaxone MIC distribution shifted away from the most susceptible (≤0.016 mg/L) and the proportion of isolates with decreased susceptibility to ceftriaxone increased significantly. This development is of concern as current European gonorrhoea management guideline recommends ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. With azithromycin resistance at 7.5%, the increasing ceftriaxone MICs might soon threaten the effectiveness of this therapeutic regimen and requires close monitoring.

  • 34.
    de Vries, H. J. C.
    et al.
    STI Outpatient Clinic, Infectious Diseases Department, Public Health Service Amsterdam, Amsterdam, The Netherlands; Department of Dermatology, Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
    de Barbeyrac, B.
    Mycoplasmal and Chlamydial Infections in Humans, University of Bordeaux, Bordeaux, France; Mycoplasmal and Chlamydial Infections in Humans, INRA, Bordeaux, France; Centre Hospitalier Universitaire de Bordeaux, Laboratoire de Bacteriologie, French National Reference Center for Bacterial STIs, Bordeaux, France.
    de Vrieze, N. H. N.
    Department of Dermatology, University Medical Centre Utrecht, Utrecht, The Netherlands.
    Viset, J. D.
    Department of Dermatology, Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
    White, J. A.
    Department of Genitourinary Medicine, Western Health & Social Care Trust, Londonderry, UK.
    Vall-Mayans, M.
    STI Unit Vall d'Hebron-Drassanes, Department of Infectious Diseases, Hospital Vall d'Hebron, Barcelona, Spain.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections.
    2019 European guideline on the management of lymphogranuloma venereum2019Ingår i: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 33, nr 10, s. 1821-1828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    New or important issues in this updated version of the 2013 European guideline on the management of lymphogranuloma venereum (LGV):

    EPIDEMIOLOGY: Lymphogranuloma venereum continues to be endemic among European men who have sex with men (MSM) since 2003. Lymphogranuloma venereum infections in heterosexuals are extremely rare in Europe, and there is no evidence of transmission of LGV in the European heterosexual population.

    AETIOLOGY AND TRANSMISSION: Chlamydia trachomatis serovars/genovars L2b and L2 are the causative strains in the majority of cases in Europe.

    CLINICAL FEATURES: Among MSM, about 25% of the anorectal LGV infections are asymptomatic. Genital infections among MSM are rare; the ratio of genital vs. anorectal LGV infections is 1 in 15.

    DIAGNOSIS: To diagnose LGV, a sample tested C. trachomatis positive with a commercial nucleic acid amplification test (NAAT) platform should be confirmed with an LGV discriminatory NAAT.

    TREATMENT: Doxycycline 100 mg twice a day orally for 21 days is the recommended treatment for LGV. This same treatment is recommended also in asymptomatic patients and contacts of LGV patients. If another regimen is used, a test of cure (TOC) must be performed.

  • 35.
    Demczuk, Walter H.B.
    et al.
    National Microbiology Laboratory, Winnipeg, Canada.
    Sidhu, S.
    National Microbiology Laboratory, Winnipeg, Canada.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University Hospital, Örebro, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.
    Whiley, David M.
    Centre for Clinical Research, The University of Queensland, Brisbane, Australia.
    Allen, Vanessa G.
    Public Health Ontario Laboratories, Toronto , Canada.
    Dillon, Jeremiah R.
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Canada.
    Cole, Michelle J.
    Public Health England, London, United Kingdom.
    Seah, Christine
    Public Health Ontario Laboratories, Toronto, Canada.
    Trembizki, Ella
    Centre for Clinical Research, The University of Queensland, Brisbane, Australia.
    Trees, David L.
    Centers for Disease Control and Prevention, Atlanta GA, United States.
    Kersh, Ellen N.
    Centers for Disease Control and Prevention, Atlanta GA, United States.
    Abrams, A. Jeanine
    Centers for Disease Control and Prevention, Atlanta GA, United States.
    de Vries, Henry J.C.
    STI Outpatient Clinic, Department of Infectious Diseases, Public Health Service Amsterdam, Amsterdam, the Netherlands; Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    van Dam, Alje P.
    Public Health Laboratory, Public Health Service Amsterdam, Amsterdam, the Netherlands; Department of Medical Microbiology, OLVG General Hospital, Amsterdam, the Netherlands; .
    Medina, I.
    National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg MB, Canada.
    Bharat, Amrita
    National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg MB, Canada.
    Mulvey, Michael Richard
    National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg MB, Canada.
    Van Domselaar, Gary
    National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg MB, Canada.
    Martin, Irene E.
    National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg MB, Canada.
    Neisseria gonorrhoeae Sequence Typing for Antimicrobial Resistance: a Novel Antimicrobial Resistance Multilocus Typing Scheme for Tracking Global Dissemination of N. gonorrhoeae Strains2017Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 55, nr 5, s. 1454-1468Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A curated Web-based user-friendly sequence typing tool based on antimicrobial resistance determinants in Neisseria gonorrhoeae was developed and is publicly accessible (https://ngstar.canada.ca). The N. gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) molecular typing scheme uses the DNA sequences of 7 genes (penA, mtrR, porB, ponA, gyrA, parC, and 23S rRNA) associated with resistance to β-lactam antimicrobials, macrolides, or fluoroquinolones. NG-STAR uses the entire penA sequence, combining the historical nomenclature for penA types I to XXXVIII with novel nucleotide sequence designations; the full mtrR sequence and a portion of its promoter region; portions of ponA, porB, gyrA, and parC; and 23S rRNA sequences. NG-STAR grouped 768 isolates into 139 sequence types (STs) (n = 660) consisting of 29 clonal complexes (CCs) having a maximum of a single-locus variation, and 76 NG-STAR STs (n = 109) were identified as unrelated singletons. NG-STAR had a high Simpson's diversity index value of 96.5% (95% confidence interval [CI] = 0.959 to 0.969). The most common STs were NG-STAR ST-90 (n = 100; 13.0%), ST-42 and ST-91 (n = 45; 5.9%), ST-64 (n = 44; 5.72%), and ST-139 (n = 42; 5.5%). Decreased susceptibility to azithromycin was associated with NG-STAR ST-58, ST-61, ST-64, ST-79, ST-91, and ST-139 (n = 156; 92.3%); decreased susceptibility to cephalosporins was associated with NG-STAR ST-90, ST-91, and ST-97 (n = 162; 94.2%); and ciprofloxacin resistance was associated with NG-STAR ST-26, ST-90, ST-91, ST-97, ST-150, and ST-158 (n = 196; 98.0%). All isolates of NG-STAR ST-42, ST-43, ST-63, ST-81, and ST-160 (n = 106) were susceptible to all four antimicrobials. The standardization of nomenclature associated with antimicrobial resistance determinants through an internationally available database will facilitate the monitoring of the global dissemination of antimicrobial-resistant N. gonorrhoeae strains.

  • 36.
    Demczuk, Walter
    et al.
    Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
    Martin, Irene
    Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
    Peterson, Shelley
    Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
    Bharat, Amrita
    Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
    Van Domselaar, Gary
    Science Technology Cores and Services Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
    Graham, Morag
    Science Technology Cores and Services Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
    Lefebvre, Brigitte
    Laboratoire de Santé Publique du Québec, Ste-Anne-de-Bellevue QC, Canada.
    Allen, Vanessa
    Public Health Ontario Laboratories, Toronto ON, Canada.
    Hoang, Linda
    British Columbia Centres for Disease Control Public Health Microbiology & Reference Laboratory, Vancouver BC, Canada.
    Tyrrell, Greg
    Provincial Laboratory for Public Health, Edmonton, Canada.
    Horsman, Greg
    Saskatchewan Disease Control Laboratory, Regina, Canada.
    Wylie, John
    Cadham Provincial Laboratory, Winnipeg, Canada.
    Haldane, David
    Queen Elizabeth II Health Sciences Centre, Halifax, Canada.
    Archibald, Chris
    Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, Canada.
    Wong, Tom
    First Nations and Inuit Health Branch, Health Canada, Ottawa, Canada.
    Unemo, Magnus
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Mulvey, Michael R
    Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
    Genomic epidemiology and molecular resistance mechanisms of azithromycin resistant Neisseria gonorrhoeae in Canada from 1997 to 20142016Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 54, nr 5, s. 1304-1313Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The emergence of Neisseria gonorrhoeae with decreased susceptibility to cephalosporins and azithromycin resistance (AZM-R) represent a public health threat of untreatable gonorrhoea infections. Genomic epidemiology through whole genome sequencing was used to describe the emergence, dissemination, and spread of AZM-R strains. The genomes of 213 AZM-R and 23 AZM-susceptible N. gonorrhoeae isolates collected in Canada from 1989 to 2014 were sequenced. Core single nucleotide polymorphism (SNP) phylogenomic analysis resolved 246 isolates into 13 lineages. High-level AZM-R (minimum inhibitory concentration ≥256 μg/ml) was found in 5 phylogenetically diverse isolates, all of which possessed the A2059G mutation (Escherichia coli numbering) in all four 23S rRNA alleles. One high-level AZM-R isolate collected in 2009 concurrently had decreased susceptibility to ceftriaxone (MIC=0.125 μg/ml). An increase in the number of 23S rRNA alleles with the C2611T mutations (E. coli numbering) conferred low to moderate AZM-R (2 to 4 and 8 to 32 μg/mL, respectively). Low level AZM-R was also associated with mtrR promoter mutations including -35A deletion and the presence of N. meningitidis-like sequences. Geographic and temporal phylogenetic clustering indicate emergent AZM-R strains arise independently and can then rapidly expand clonally in a region through local sexual networks.

  • 37. Domeika, M.
    et al.
    Litvinenko, I.
    Smirnova, T.
    Gaivaronskaya, O.
    Savicheva, A.
    Sokolovskiy, E.
    Ballard, R. C.
    Unemo, Magnus
    Örebro universitet, Hälsoakademin.
    Laboratory diagnostics for non-viral sexually transmitted infections in St. Petersburg, Russia: current situation and hallmarks for improvements2008Ingår i: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 22, nr 9, s. 1094-1100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The numbers and performance characteristics of laboratories providing sexually transmitted infection (STI) diagnostic services, as well as the rates of morbidity due to STIs in St. Petersburg, Russia, remain largely unknown.

    OBJECTIVE: The aim of the present study was to evaluate the range, quality and availability of diagnostic services for several non-viral STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum and Trichomonas vaginalis) in St. Petersburg during the period September 2005 to June 2006.

    METHODS: Survey data focusing on organization and performance characteristics of STI diagnostic services were assessed using questionnaires, telephone interviews and site visits.

    RESULTS: A total of 118 laboratories providing STI diagnostic services were identified. Of the surveyed laboratories, 54% (64 of 118) diagnosed syphilis, 81% (96 of 118) gonorrhoea, 80% (94 of 118) trichomoniasis and 49% (58 of 118) chlamydial infections. Although most of the laboratories could provide a presumptive diagnosis for syphilis, most of the N. gonorrhoeae and T. vaginalis testing of women did not adhere to international recommendations. Of the laboratories with the capacity to diagnose C. trachomatis infection, 69% still used serological testing (enzyme-linked immunosorbent assay) to detect antibodies to C. trachomatis.

    CONCLUSIONS: Overall, the diagnostic methods used to establish a laboratory diagnosis, the system of case reporting, the training of laboratory personnel and the level of interlaboratory communication clearly require improvement. This study represents the first step in a process of evaluation of the laboratory support for STI services and the establishment of an interlaboratory network in St. Petersburg.

  • 38.
    Donachie, Alastair
    et al.
    Infectious Disease Prevention and Control Unit (IDCU) – Health Promotion and Disease Prevention Directorate, Valletta, Malta; European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.
    Barbara, Christopher
    Department of Pathology, Mater Dei Hospital, Msida, Malta.
    Mellilo, Tanya
    Infectious Disease Prevention and Control Unit (IDCU) – Health Promotion and Disease Prevention Directorate, Valletta, Malta.
    Hadad, Ronza
    WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Farrugia, Alexandra Gauci
    Genitourinary Clinic, Mater Dei Hospital, Msida, Malta.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs.
    Padovese, Valeska
    Genitourinary Clinic, Mater Dei Hospital, Msida, Malta.
    Lymphogranuloma venereum (LGV) in men who have sex with men (MSM): a re-emerging problem, Malta, 20182018Ingår i: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 23, nr 43, s. 2-6, artikel-id 1800541Artikel i tidskrift (Refereegranskat)
  • 39.
    Donà, Valentina
    et al.
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Kasraian, Sara
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Lupo, Agnese
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Guilarte, Yuvia N.
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Hauser, Christoph
    Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
    Furrer, Hansjakob
    Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
    Unemo, Magnus
    Örebro universitet, Institutionen för hälsovetenskaper.
    Low, Nicola
    Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
    Endimiani, Andrea
    Institute for Infectious Diseases, University of Bern, Bern, Switzerlanda.
    Multiplex real-time PCR assay with high-resolution melting analysis for characterization of antimicrobial resistance in neisseria gonorrhoeae2016Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 54, nr 8, s. 2074-2081Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Resistance to antibiotics used against Neisseria gonorrhoeae infections is a major public health concern. Antimicrobial resistance (AMR) testing relies on time-consuming culture-based methods. Development of rapid molecular tests for detecting AMR determinants could provide valuable tools for surveillance, epidemiological studies and to inform individual case management. We developed a fast (<1.5 hrs) SYBR-green based real-time PCR method with high resolution melting (HRM) analysis. One triplex and three duplex reactions included two sequences for N. gonorrhoeae identification and seven determinants of resistance to extended-spectrum cephalosporins (ESCs), azithromycin, ciprofloxacin, and spectinomycin. The method was validated by testing 39 previously fully-characterized N. gonorrhoeae strains, 19 commensal Neisseria spp., and an additional panel of 193 gonococcal isolates. Results were compared with culture-based AMR determination. The assay correctly identified N. gonorrhoeae and the presence or absence of the seven AMR determinants. There was some cross-reactivity with non-gonococcal Neisseria species and the detection limit was 10(3)-10(4) gDNA copies/reaction. Overall, the platform accurately detected resistance to ciprofloxacin (sensitivity and specificity, 100%), ceftriaxone (sensitivity 100%, specificity 90%), cefixime (sensitivity 92%, specificity 94%), azithromycin and spectinomycin (both sensitivity and specificity, 100%). In conclusion, our methodology accurately detects mutations generating resistance to antibiotics used to treat gonorrhea. Low assay sensitivity prevents direct diagnostic testing of clinical specimens but this method can be used to screen collections of gonococcal isolates for AMR more quickly than with current culture-based AMR testing.

  • 40.
    Donà, Valentina
    et al.
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Low, Nicola
    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Golparian, Daniel
    Örebro universitet, Institutionen för medicinska vetenskaper. WHO Collaborating Centre for Gonorrhoea, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea, Örebro University Hospital, Örebro, Sweden.
    Recent advances in the development and use of molecular tests to predict antimicrobial resistance in Neisseria gonorrhoeae2017Ingår i: Expert Review of Molecular Diagnostics, ISSN 1473-7159, E-ISSN 1744-8352, Vol. 17, nr 9, s. 845-859Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: The number of genetic tests, mostly real-time PCRs, to detect antimicrobial resistance (AMR) determinants and predict AMR in Neisseria gonorrhoeae is increasing. Several of these assays are promising, but there are important shortcomings and few assays have been adequately validated and quality assured.

    Areas covered: Recent advances, focusing on publications since 2012, in the development and use of molecular tests to predict gonococcal AMR for surveillance and for clinical use, advantages and disadvantages of these tests and of molecular AMR prediction compared with phenotypic AMR testing, and future perspectives for effective use of molecular AMR tests for different purposes.

    Expert commentary: Several challenges for direct testing of clinical, especially extra-genital, specimens remain. The choice of molecular assay needs to consider the assay target, quality controls, sample types, limitations intrinsic to molecular technologies, and specific to the chosen methodology, and the intended use of the test. Improved molecular- and particularly genome-sequencing-based methods will supplement AMR testing for surveillance purposes, and translate into point-of-care tests that will lead to personalized treatments, while sparing the last available empiric treatment option (ceftriaxone). However, genetic AMR prediction will never completely replace phenotypic AMR testing, which detects also AMR due to unknown AMR determinants.

  • 41.
    Donà, Valentina
    et al.
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Smid, Joost H.
    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Kasraian, Sara
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Egli-Gany, Dianne
    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Dost, Ferah
    Ambulatorium Kanonengasse, Zurich, Switzerland.
    Imeri, Fatime
    Laborgemeinschaft 1, Zurich, Switzerland.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and other STIs, Örebro University Hospital, Örebro, Sweden.
    Low, Nicola
    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Endimiani, Andrea
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Mismatch Amplification Mutation Assay (MAMA)-Based Real-Time PCR for Rapid Detection of Neisseria gonorrhoeae and Antimicrobial Resistance Determinants in Clinical Specimens2018Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 56, nr 9, artikel-id e00365-18Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Molecular methods are often used for Neisseria gonorrhoeae (NG) detection, but complete definition of antimicrobial resistance (AMR) patterns still requires phenotypic tests. We developed an assay that both identifies NG and detects AMR determinants in clinical specimens.We designed a mismatch amplification mutation assay (MAMA)-based SYBR Green real-time PCR targeting: one NG-specific region (opa); mosaic penA alleles (Asp345 deletion, Gly545Ser) associated with decreased susceptibility to cephalosporins; alterations conferring resistance to ciprofloxacin (GyrA: Ser91Phe), azithromycin (23S rRNA: A2059G and C2611T) and spectinomycin (16S rRNA: C1192T). We applied the real-time PCR to 489 clinical specimens, of which 94 had paired culture isolates, and evaluated its performance by comparison with commercial diagnostic molecular and phenotypic tests.Our assay exhibited a sensitivity/specificity of 93%/100%, 96%/85%, 90%/91%, 100%/100% and 100%/90% for the detection of NG directly from urethral, rectal, pharyngeal, cervical and vaginal samples, respectively. The MAMA strategy allowed the detection of AMR mutations by comparing cycle threshold values with the reference opa reaction. The method accurately predicted the phenotype to four antibiotic classes when compared with the MIC values obtained from 94 paired cultures (sensitivity/specificity for cephalosporins, azithromycin, ciprofloxacin and spectinomycin resistance: 100%/95%, 100%/100%, 100%/100% and not applicable (NA)/100%, respectively, in genital specimens; NA/72%, NA/98%, 100%/97%, and NA/96%, respectively, in extra-genital specimens). False-positive results, particularly for the penA Asp345del reaction were observed predominantly in pharyngeal specimens.Our real-time PCR assay is a promising rapid method to identify NG and predict AMR directly in genital specimens, but further optimization for extra-genital specimens is needed.

  • 42.
    El-Rami, Fadi E.
    et al.
    Pharmaceutical Sciences, Oregon State University, United States of America.
    Zielke, Ryszard A.
    College of Pharmacy, Oregon State University, United States of America.
    Wi, Teodora
    World Health Organization, Geneva, Switzerland.
    Sikora, Aleksandra E.
    Department of Pharmaceutical Sciences, Oregon State University, United States of America; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton OR, United States.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. World Health Organization, Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology.
    Quantitative proteomics of the 2016 WHO Neisseria gonorrhoeae reference strains surveys vaccine candidates and antimicrobial resistance determinants2019Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, nr 1, s. 127-150Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The sexually transmitted disease gonorrhea (causative agent: Neisseria gonorrhoeae) remains an urgent public health threat globally due to its reproductive health repercussions, high incidence, widespread antimicrobial resistance (AMR), and absence of a vaccine. To mine gonorrhea antigens and enhance our understanding of gonococcal AMR at the proteome level, we performed the first large-scale proteomic profiling of a diverse panel (n=15) of gonococcal strains, including the 2016 World Health Organization (WHO) reference strains. These strains show all existing AMR profiles - established through phenotypic characterization and reference genome publication - and are intended for quality assurance in laboratory investigations. Herein, these isolates were subjected to subcellular fractionation and labeling with tandem mass tags coupled to mass spectrometry and multi-combinatorial bioinformatics. Our analyses detected 904 and 723 common proteins in cell envelope and cytoplasmic subproteomes, respectively. We identified nine novel gonorrhea vaccine candidates. Expression and conservation of new and previously selected antigens were investigated. In addition, established gonococcal AMR determinants were evaluated for the first time using quantitative proteomics. Six new proteins, WHO_F_00238, WHO_F_00635c, WHO_F_00745, WHO_F_01139, WHO_F_01144c, and WHO_F_01126, were differentially expressed in all strains, suggesting that they represent global proteomic AMR markers, indicate a predisposition toward developing or compensating gonococcal AMR, and/or act as new antimicrobial targets. Finally, phenotypic clustering based on the isolates' defined antibiograms and common differentially expressed proteins yielded seven matching clusters between established and proteome-derived AMR signatures. Together, our investigations provide a reference proteomics databank for gonococcal vaccine and AMR research endeavors, which enables microbiological, clinical, or epidemiological projects and enhances the utility of the WHO reference strains.

  • 43.
    Eyre, David W.
    et al.
    Big Data Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
    Sanderson, Nicholas D.
    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
    Lord, Emily
    Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
    Regisford-Reimmer, Natasha
    Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
    Chau, Kevin
    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
    Barker, Leanne
    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
    Morgan, Markus
    Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
    Newnham, Robert
    Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
    Golparian, Daniel
    Örebro universitet, Institutionen för medicinska vetenskaper. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Örebro University Hospital, Örebro, Sweden.
    Crook, Derrick W.
    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; National Infection Service, Public Health England, Colindale, United Kingdom; National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, United Kingdom .
    Peto, Tim E. A.
    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, United Kingdom.
    Hughes, Gwenda
    National Infection Service, Public Health England, Colindale, United Kingdom.
    Cole, Michelle J.
    National Infection Service, Public Health England, Colindale, United Kingdom.
    Fifer, Helen
    National Infection Service, Public Health England, Colindale, United Kingdom.
    Edwards, Anne
    Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
    Andersson, Monique I.
    Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
    Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 20182018Ingår i: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 23, nr 27, s. 2-7, artikel-id 1800323Artikel i tidskrift (Refereegranskat)
  • 44.
    Ezewudo, Matthew N.
    et al.
    Sch Med, Dept Med, Div Infect Dis, Emory Univ, Atlanta GA, USA.
    Joseph, Sandeep J.
    Sch Med, Dept Med, Div Infect Dis, Emory Univ, Atlanta GA, USA.
    Castillo-Ramirez, Santiago
    Ctr Ciencias Genom, Programa Genom Evolut, Univ Nacl Autonoma Mexico, Cuernavaca, Mexico.
    Dean, Deborah
    Oakland Res Inst, Childrens Hosp, Oakland CA, USA; Div Infect Dis, Univ Calif, San Francisco CA, USA.
    del Rio, Carlos
    Sch Med, Dept Med, Div Infect Dis, Emory Univ, Atlanta GA, USA; Hubert Dept Global Hlth, Rollins Sch Publ Hlth, Emory Univ, Atlanta GA, USA.
    Didelot, Xavier
    Sci Technol & Med, Dept Infect Dis Epidemiol, Univ London Imperial College, London, England.
    Dillon, Jo-Anne
    Coll Med, Dept Microbiol & Immunol, Vaccine & Infect Dis Org Int Vaccine Ctr, Univ Saskatchewan, Saskatoon SK, Canada.
    Selden, Richard F.
    NetBio, Waltham MA, USA.
    Shafer, William M.
    Sch Med, Dept Microbiol & Immunol, Emory Univ, Atlanta GA, USA; Labs Bacterial Pathogenesis, Vet Affairs Med Ctr, Decatur GA, USA.
    Turingan, Rosemary S.
    NetBio, Waltham MA, USA.
    Unemo, Magnus
    Region Örebro län. WHO Collaborating Ctr Gonorrhoea & Other STIs, Örebro University Hospital, Örebro, Sweden.
    Read, Timothy D.
    Sch Med, Dept Med, Div Infect Dis, Emory Univ, Atlanta GA, USA.
    Population structure of Neisseria gonorrhoeae based on whole genome data and its relationship with antibiotic resistance2015Ingår i: PeerJ, ISSN 2167-8359, E-ISSN 2167-8359, Vol. 3, artikel-id e806Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neisseria gonorrhoeae is the causative agent of gonorrhea, a sexually transmitted infection (STI) of major importance. As a result of antibiotic resistance, there are now limited options for treating patients. We collected draft genome sequence data and associated metadata data on 76 N. gonorrhoeae strains from around the globe and searched for known determinants of antibiotics resistance within the strains. The population structure and evolutionary forces within the pathogen population were analyzed. Our results indicated a cosmopolitan gonoccocal population mainly made up of five subgroups. The estimated ratio of recombination to mutation (r/m = 2.2) from our data set indicates an appreciable level of recombination occurring in the population. Strains with resistance phenotypes to more recent antibiotics (azithromycin and cefixime) were mostly found in two of the five population subgroups.

  • 45.
    Fifer, Helen
    et al.
    Public Health England, London, United Kingdom.
    Natarajan, Usha
    Virgin Care, London, United Kingdom.
    Jones, Lucy
    Virgin Care, London, United Kingdom.
    Alexander, Sarah
    Public Health England, London, United Kingdom.
    Hughes, Gwenda
    Public Health England, London, United Kingdom.
    Golparian, Daniel
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Unemo, Magnus
    Örebro universitet, Institutionen för hälsovetenskaper.
    Failure of Dual Antimicrobial Therapy in Treatment of Gonorrhea2016Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 374, nr 25, s. 2504-2506Artikel i tidskrift (Refereegranskat)
  • 46.
    Foerster, Sunniva
    et al.
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; WHO Collaborating Centre for Gonorrhoea and other STIs, Örebro University, Örebro, Sweden; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
    Desilvestro, Valentino
    World Trade Institute (WTI), University of Bern, Bern, Switzerland.
    Hathaway, Lucy J
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Althaus, Christian L
    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Unemo, Magnus
    Region Örebro län. WHO Collaborating Centre for Gonorrhoea and other STIs, Örebro University Hospital, Örebro, Sweden.
    A new rapid resazurin-based microdilution assay for antimicrobial susceptibility testing of Neisseria gonorrhoeae2017Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 72, nr 7, s. 1961-1968Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Rapid, cost-effective and objective methods for antimicrobial susceptibility testing of Neisseria gonorrhoeae would greatly enhance surveillance of antimicrobial resistance. Etest, disc diffusion and agar dilution methods are subjective, mostly laborious for large-scale testing and take ∼24 h. We aimed to develop a rapid broth microdilution assay using resazurin (blue), which is converted into resorufin (pink fluorescence) in the presence of viable bacteria.

    Methods: The resazurin-based broth microdilution assay was established using 132 N. gonorrhoeae strains and the antimicrobials ceftriaxone, cefixime, azithromycin, spectinomycin, ciprofloxacin, tetracycline and penicillin. A regression model was used to estimate the MICs. Assay results were obtained in ∼7.5 h.

    Results: The EC 50 of the dose-response curves correlated well with Etest MIC values (Pearson's r  = 0.93). Minor errors resulting from misclassifications of intermediate strains were found for 9% of the samples. Major errors (susceptible strains misclassified as resistant) occurred for ceftriaxone (4.6%), cefixime (3.3%), azithromycin (0.6%) and tetracycline (0.2%). Only one very major error was found (a ceftriaxone-resistant strain misclassified as susceptible). Overall the sensitivity of the assay was 97.1% (95% CI 95.2-98.4) and the specificity 78.5% (95% CI 74.5-82.9).

    Conclusions: A rapid, objective, high-throughput, quantitative and cost-effective broth microdilution assay was established for gonococci. For use in routine diagnostics without confirmatory testing, the specificity might remain suboptimal for ceftriaxone and cefixime. However, the assay is an effective low-cost method to evaluate novel antimicrobials and for high-throughput screening, and expands the currently available methodologies for surveillance of antimicrobial resistance in gonococci.

  • 47.
    Foerster, Sunniva
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, Örebro, Sweden.
    Drusano, George
    University of Florida, Orlando, USA.
    Golparian, Daniel
    Örebro universitet, Institutionen för medicinska vetenskaper. WHO Collaborating Centre for Gonorrhoea and Other STIs.
    Neely, Michael
    University of Southern California, Los Angeles, USA.
    Piddock, Laura
    Global Antibiotic Research and Development Partnership (GARDP), Geneva, Switzerland.
    Alirol, Emilie
    Global Antibiotic Research and Development Partnership (GARDP), Geneva, Switzerland.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. World Health Organization Collaborating Centre for Gonorrhoea and Other STIs.
    IN VITRO COMBINATION TESTING AND SELECTION OF RESISTANCE TO ZOLIFLODACIN COMBINED WITH SIX ANTIMICROBIALS FOR N. GONORRHOEAE2019Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, nr Suppl. 1, s. A50-A50Artikel i tidskrift (Övrigt vetenskapligt)
  • 48.
    Foerster, Sunniva
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, Swedish Reference Laboratory for STIs, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Drusano, George
    Institute for Therapeutic Innovation, Department of Medicine, College of Medicine, University of Florida, Orlando, FL, USA.
    Golparian, Daniel
    Örebro universitet, Institutionen för medicinska vetenskaper. WHO Collaborating Centre for Gonorrhoea and other STIs, Swedish Reference Laboratory for STIs.
    Neely, Michael
    Children's Hospital of Los Angeles, Department of Pediatrics, Division of Infectious Diseases, University of Southern California, CA, USA.
    Piddock, Laura J. V.
    Global Antibiotic Research & Development Partnership (GARDP), Geneva, Switzerland.
    Alirol, Emilie
    Global Antibiotic Research & Development Partnership (GARDP), Geneva, Switzerland.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and other STIs, Swedish Reference Laboratory for STIs.
    In vitro antimicrobial combination testing of and evolution of resistance to the first-in-class spiropyrimidinetrione zoliflodacin combined with six therapeutically relevant antimicrobials for Neisseria gonorrhoeae2019Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, nr 12, s. 3521-3529Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Resistance in Neisseria gonorrhoeae to all gonorrhoea therapeutic antimicrobials has emerged. Novel therapeutic antimicrobials are imperative and the first-in-class spiropyrimidinetrione zoliflodacin appears promising. Zoliflodacin could be introduced in dual antimicrobial therapies to prevent the emergence and/or spread of resistance. We investigated the in vitro activity of and selection of resistance to zoliflodacin alone and in combination with six gonorrhoea therapeutic antimicrobials against N. gonorrhoeae.

    METHODS: The international gonococcal reference strains WHO F (WT) and WHO O, WHO V and WHO X (strains with different AMR profiles) were examined. Zoliflodacin was evaluated alone or combined with ceftriaxone, cefixime, spectinomycin, gentamicin, tetracycline, cethromycin or sitafloxacin in chequerboard assays, time-kill curve analysis and selection-of-resistance studies.

    RESULTS: Zoliflodacin alone or in combination with all six antimicrobials showed rapid growth inhibition against all examined strains. The time-kill curve analysis indicated that tetracycline or cethromycin combined with zoliflodacin can significantly decrease the zoliflodacin kill rate in vitro. The frequency of selected zoliflodacin-resistance mutations was low when evaluated as a single agent and further reduced for all antimicrobial combinations. All resistant mutants contained the GyrB mutations D429N, K450T or K450N, resulting in zoliflodacin MICs of 0.5-4 mg/L.

    CONCLUSIONS: Zoliflodacin, alone or in combination with sexually transmitted infection therapeutic antimicrobials, rapidly kills gonococci with infrequent resistance emergence. Zoliflodacin remains promising for gonorrhoea oral monotherapy and as part of dual antimicrobial therapy with low resistance emergence potential. A Phase III trial evaluating efficacy and safety of zoliflodacin for uncomplicated gonorrhoea treatment is planned in 2019.

  • 49.
    Foerster, Sunniva
    et al.
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Golparian, Daniel
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro universitet, Institutionen för hälsovetenskap och medicin. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Hathaway, Lucy J.
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Low, Nicola
    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Shafer, William M.
    Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta GA, USA; Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center, Decatur GA, USA.
    Althaus, Christian L.
    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Unemo, Magnus
    Örebro universitet, Institutionen för hälsovetenskap och medicin. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Genetic Resistance Determinants, In Vitro Time-Kill Curve Analysis and Pharmacodynamic Functions for the Novel Topoisomerase II Inhibitor ETX0914 (AZD0914) in Neisseria gonorrhoeae2015Ingår i: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 6, artikel-id 1377Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Resistance in Neisseria gonorrhoeae to all available therapeutic antimicrobials has emerged and new efficacious drugs for treatment of gonorrhea are essential. The topoisomerase II inhibitor ETX0914 (also known as AZD0914) is a new spiropyrimidinetrione antimicrobial that has different mechanisms of action from all previous and current gonorrhea treatment options. In this study, the N. gonorrhoeae resistance determinants for ETX0914 were further described and the effects of ETX0914 on the growth of N. gonorrhoeae (ETX0914 wild type, single step selected resistant mutants, and efflux pump mutants) were examined in a novel in vitro time-kill curve analysis to estimate pharmacodynamic parameters of the new antimicrobial. For comparison, ciprofloxacin, azithromycin, ceftriaxone, and tetracycline were also examined (separately and in combination with ETX0914). ETX0914 was rapidly bactericidal for all wild type strains and had similar pharmacodynamic properties to ciprofloxacin. All selected resistant mutants contained mutations in amino acid codons D429 or K450 of GyrB and inactivation of the MtrCDE efflux pump fully restored the susceptibility to ETX0914. ETX0914 alone and in combination with azithromycin and ceftriaxone was highly effective against N. gonorrhoeae and synergistic interaction with ciprofloxacin, particularly for ETX0914-resistant mutants, was found. ETX0914, monotherapy or in combination with azithromycin (to cover additional sexually transmitted infections), should be considered for phase III clinical trials and future gonorrhea treatment.

  • 50.
    Foerster, Sunniva
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
    Gustafsson, Tomas N.
    Department of Clinical Microbiology, Sunderby Research Unit, Umeå University, Umeå, Sweden.
    Rita Brochado, Anna
    European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
    Desilvestro, Valentino
    World Trade Institute (WTI), University of Bern, Bern, Switzerland.
    Typas, Athanasios
    European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    The first wide-scale drug repurposing screen using the Prestwick Chemical Library (1200 bioactive molecules) against Neisseria gonorrhoeae identifies high in vitro activity of auranofin and many additional drugs2020Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Treatment options for gonorrhoea are scarce. Drug repurposing of bioactive molecules approved for other conditions might therefore be of value. We developed a method for wide-scale, systematic drug repurposing screen to identify molecules with activity against Neisseria gonorrhoeae and screened the Prestwick Chemical Library (1200 FDA-approved drugs). As a proof-of-concept, we further examined one promising and interesting screening hit (auranofin; antirheumatic agent). Three WHO gonococcal reference strains (WHO F, O, P) were used for the Library screening. The strains were grown in presence of a fixed concentration of the library drugs in 384-well plates for 12 hours and the remaining bacterial respiration, to reflect growth, was then quantitatively measured using optical density (OD) 450 nm and a resazurin assay. The activity of auranofin was further examined using in vitro susceptibility testing (minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)) against genetically diverse antimicrobial-resistant N. gonorrhoeae strains and time-kill assays. Sixty-eight molecules significantly inhibited bacterial growth of WHO F, O and, P. Auranofin showed potent in vitro bactericidal activity (in MIC-, MBC-, and time-kill assays) against four WHO reference strains. No cross resistance between auranofin and any antimicrobial currently or previously used for gonorrhoea treatment was found when examining 51 selected antimicrobial-resistant gonococcal strains. In conclusion, this is the first wide-scale systematic screening effort for repurposing drugs for future treatment of gonorrhoea. Additional studies examining mechanism(s) of action, resistance development, in vivo anti-gonococcal activity, and pharmacokinetics/pharmacodynamics for gonococcal infections of auranofin and several other significant screening hits would be valuable.

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