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Lan, P. T., Golparian, D., Ringlander, J., Van Hung, L., Van Thuong, N. & Unemo, M. (2020). Genomic analysis and antimicrobial resistance of Neisseria gonorrhoeae isolates from Vietnam in 2011 and 2015-16. Journal of Antimicrobial Chemotherapy, Article ID dkaa040.
Open this publication in new window or tab >>Genomic analysis and antimicrobial resistance of Neisseria gonorrhoeae isolates from Vietnam in 2011 and 2015-16
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2020 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, article id dkaa040Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVES: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae, compromising gonorrhoea treatment, is a threat to reproductive health globally. South-East and East Asia have been major sources of emergence and subsequent international spread of AMR gonococcal strains during recent decades. We investigated gonococcal isolates from 2011 and 2015-16 in Vietnam using AMR testing, WGS and detection of AMR determinants.

METHODS: Two hundred and twenty-nine gonococcal isolates cultured in 2015-16 (n = 121) and 2011 (n = 108) in Vietnam were examined. AMR testing was performed using Etest and WGS with Illumina MiSeq.

RESULTS: Resistance among the 2015-16 isolates was as follows: ciprofloxacin, 100%; tetracycline, 79%; benzylpenicillin, 50%; cefixime, 15%; ceftriaxone, 1%; spectinomycin, 0%; and 5% were non-WT to azithromycin. Eighteen (15%) isolates were MDR. The MIC range for gentamicin was 2-8 mg/L. Among the 2015-16 isolates, 27% (n = 33) contained a mosaic penA allele, while no isolates had a mosaic penA allele in 2011. Phylogenomic analysis revealed introduction after 2011 of two mosaic penA-containing clones (penA-10.001 and penA-34.001), which were related to cefixime-resistant strains spreading in Japan and Europe, and a minor clade (eight isolates) relatively similar to the XDR strain WHO Q.

CONCLUSIONS: From 2011 to 2015-16, resistance in gonococci from Vietnam increased to all currently and previously used antimicrobials except ceftriaxone, spectinomycin and tetracycline. Two mosaic penA-containing clones were introduced after 2011, explaining the increased cefixime resistance. Significantly increased AMR surveillance, antimicrobial stewardship and use of WGS for molecular epidemiology and AMR prediction for gonococcal isolates in Vietnam and other Asian countries are crucial.

Place, publisher, year, edition, pages
Oxford University Press, 2020
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-80179 (URN)10.1093/jac/dkaa040 (DOI)32068837 (PubMedID)
Available from: 2020-02-25 Created: 2020-02-25 Last updated: 2020-02-25Bibliographically approved
Golparian, D., Harris, S. R., Sánchez-Busó, L., Hoffmann, S., Shafer, W. M., Bentley, S. D., . . . Unemo, M. (2020). Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928-2013): antimicrobial use/misuse selects for resistance and drives evolution. BMC Genomics, 21(1), Article ID 116.
Open this publication in new window or tab >>Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928-2013): antimicrobial use/misuse selects for resistance and drives evolution
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2020 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 21, no 1, article id 116Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Multidrug-resistant Neisseria gonorrhoeae strains are prevalent, threatening gonorrhoea treatment globally, and understanding of emergence, evolution, and spread of antimicrobial resistance (AMR) in gonococci remains limited. We describe the genomic evolution of gonococci and their AMR, related to the introduction of antimicrobial therapies, examining isolates from 1928 (preantibiotic era) to 2013 in Denmark. This is, to our knowledge, the oldest gonococcal collection globally.

METHODS: Lyophilised isolates were revived and examined using Etest (18 antimicrobials) and whole-genome sequencing (WGS). Quality-assured genome sequences were obtained for 191 viable and 40 non-viable isolates and analysed with multiple phylogenomic approaches.

RESULTS: Gonococcal AMR, including an accumulation of multiple AMR determinants, started to emerge particularly in the 1950s-1970s. By the twenty-first century, resistance to most antimicrobials was common. Despite that some AMR determinants affect many physiological functions and fitness, AMR determinants were mainly selected by the use/misuse of gonorrhoea therapeutic antimicrobials. Most AMR developed in strains belonging to one multidrug-resistant (MDR) clade with close to three times higher genomic mutation rate. Modern N. gonorrhoeae was inferred to have emerged in the late-1500s and its genome became increasingly conserved over time.

CONCLUSIONS: WGS of gonococci from 1928 to 2013 showed that no AMR determinants, except penB, were in detectable frequency before the introduction of gonorrhoea therapeutic antimicrobials. The modern gonococcus is substantially younger than previously hypothesized and has been evolving into a more clonal species, driven by the use/misuse of antimicrobials. The MDR gonococcal clade should be further investigated for early detection of strains with predispositions to develop and maintain MDR and for initiation of public health interventions.

Place, publisher, year, edition, pages
BioMed Central, 2020
Keywords
Antimicrobial resistance, Evolution, Genomic epidemiology, Neisseria gonorrhoeae, Temporal analysis, Whole-genome sequencing
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-79946 (URN)10.1186/s12864-020-6511-6 (DOI)000521339000002 ()32013864 (PubMedID)2-s2.0-85078901790 (Scopus ID)
Funder
Wellcome trust, 098051
Note

Funding Agencies:

Örebro County Council Research Committee  

Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden  

Örebro University 

Available from: 2020-02-19 Created: 2020-02-19 Last updated: 2020-04-14Bibliographically approved
Silveira, M. F., Bruni, M. P., Stauffert, D., Golparian, D. & Unemo, M. (2020). Prevalence and risk factors associated with Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium among women in Pelotas, Southern Brazil. International Journal of STD and AIDS (London), 31(5), 432-439
Open this publication in new window or tab >>Prevalence and risk factors associated with Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium among women in Pelotas, Southern Brazil
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2020 (English)In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 31, no 5, p. 432-439Article in journal (Refereed) Published
Abstract [en]

The frequently asymptomatic sexually transmitted infections (STIs) caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) are poorly diagnosed in Brazil and can lead to severe complications/sequelae without timely detection and treatment. We investigated prevalence of CT, NG, and MG infections and associated demographic, behavioral, and clinical factors in consecutive women attending a gynecology and obstetrics outpatient clinic in Pelotas, Southern Brazil. Vaginal swab samples were prospectively obtained from asymptomatic and symptomatic women (n = 498) from August 2015 to December 2016 and tested with Aptima Combo2 and Aptima M. genitalium assays (Hologic). The prevalence of CT, NG, and MG was 6.8% (34/498), 1.0% (5/498), and 4.2% (21/498), respectively. Three (0.6%) cases of CT and NG co-infection and one (0.2%) case of CT and MG co-infection were identified. The risk factors associated with these bacterial STIs were youth (<30 years), no steady sexual partner, infection with additional STI, and lack of income. Bacterial STIs, particularly CT and MG, were prevalent among women, including pregnant women (60% of positive cases), in Pelotas, Brazil. Sensitive and specific diagnostic testing and early treatment are essential to control STIs, limit transmission chains, avoid future complications/sequelae, and reduce health and cost burdens on the population.

Place, publisher, year, edition, pages
Sage Publications, 2020
Keywords
Brazil, Sexually transmitted infections, diagnosis, screening, women
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-80805 (URN)10.1177/0956462419898982 (DOI)000523042200006 ()32192370 (PubMedID)2-s2.0-85082177278 (Scopus ID)
Available from: 2020-03-23 Created: 2020-03-23 Last updated: 2020-04-20Bibliographically approved
Boiko, I., Golparian, D., Krynytska, I., Bezkorovaina, H., Frankenberg, A., Onuchyna, M., . . . Unemo, M. (2019). Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-2018. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 127(7), 503-509
Open this publication in new window or tab >>Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-2018
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2019 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 7, p. 503-509Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
Neisseria gonorrhoeae, Gonorrhoea, antimicrobial resistance (AMR), ceftriaxone, azithromycin, Ukraine
National Category
Immunology in the medical area Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-75208 (URN)10.1111/apm.12948 (DOI)000473620900002 ()30903707 (PubMedID)
Available from: 2019-07-26 Created: 2019-07-26 Last updated: 2019-07-26Bibliographically approved
Bruni, M. P., Freitas da Silveira, M., Stauffert, D., Bicca, G. L., Caetano Dos Santos, C., da Rosa Farias, N. A., . . . Unemo, M. (2019). Aptima Trichomonas vaginalis assay elucidates significant underdiagnosis of trichomoniasis among women in Brazil according to an observational study. Sexually Transmitted Infections, 95(2), 129-132
Open this publication in new window or tab >>Aptima Trichomonas vaginalis assay elucidates significant underdiagnosis of trichomoniasis among women in Brazil according to an observational study
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2019 (English)In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, no 2, p. 129-132Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
Keywords
Aptima, Brazil, culture, nucleic acid amplification test (NAAT), trichomonas infection, trichomonas vaginalis, wet mount microscopy
National Category
Obstetrics, Gynecology and Reproductive Medicine Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-68678 (URN)10.1136/sextrans-2018-053635 (DOI)000471868700012 ()30154157 (PubMedID)2-s2.0-85052888876 (Scopus ID)
Note

Funding Agencies:

Programa de Apoio a Pos-Graduacao (PROAP)  

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brasilia, DF, Brazil  

Örebro County Council Research Committee  

Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden 

Available from: 2018-09-03 Created: 2018-09-03 Last updated: 2019-11-08Bibliographically approved
Sánchez-Busó, L., Golparian, D., Parkhill, J., Unemo, M. & Harris, S. R. (2019). Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae. Scientific Reports, 9(1), Article ID 14685.
Open this publication in new window or tab >>Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 14685Article in journal (Refereed) Published
Abstract [en]

Restriction-Modification systems (RMS) are one of the main mechanisms of defence against foreign DNA invasion and can have an important role in the regulation of gene expression. The obligate human pathogen Neisseria gonorrhoeae carries one of the highest loads of RMS in its genome; between 13 to 15 of the three main types. Previous work has described their organization in the reference genome FA1090 and has inferred the associated methylated motifs. Here, we studied the structure of RMS and target methylated motifs in 25 gonococcal strains sequenced with Single Molecule Real-Time (SMRT) technology, which provides data on DNA modification. The results showed a variable picture of active RMS in different strains, with phase variation switching the activity of Type III RMS, and both the activity and specificity of a Type I RMS. Interestingly, the Dam methylase was found in place of the NgoAXI endonuclease in two of the strains, despite being previously thought to be absent in the gonococcus. We also identified the real methylation target of NgoAXII as 5'-GCAGA-3', different from that previously described. Results from this work give further insights into the diversity and dynamics of RMS and methylation patterns in N. gonorrhoeae.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-77256 (URN)10.1038/s41598-019-51102-2 (DOI)000489701600021 ()31605008 (PubMedID)2-s2.0-85073164375 (Scopus ID)
Note

Funding Agency:

Wellcome Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden 098051

Available from: 2019-10-14 Created: 2019-10-14 Last updated: 2019-10-25Bibliographically approved
Gianecini, R. A., Golparian, D., Zittermann, S., Litvik, A., Gonzalez, S., Oviedo, C., . . . Galarza, P. (2019). Genome-based epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates with decreased susceptibility and resistance to extended-spectrum cephalosporins in Argentina in 2011-16. Journal of Antimicrobial Chemotherapy, 74(6), 1551-1559
Open this publication in new window or tab >>Genome-based epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates with decreased susceptibility and resistance to extended-spectrum cephalosporins in Argentina in 2011-16
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2019 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, no 6, p. 1551-1559Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Our aim was to describe the molecular epidemiology and antimicrobial resistance determinants of isolates of Neisseria gonorrhoeae with decreased susceptibility and resistance to extended-spectrum cephalosporins (ESCs) in Argentina in 2011-16.

METHODS: Gonococcal isolates (n = 158) with decreased susceptibility and resistance to ESCs collected in 2011-16 across Argentina were subjected to WGS and antimicrobial susceptibility testing for six antimicrobials.

RESULTS: In total, 50% of the isolates were resistant to cefixime, 1.9% were resistant to ceftriaxone, 37.3% were resistant to azithromycin and 63.9% of the isolates showed an MDR phenotype. Resistance and decreased susceptibility to ESCs was mainly associated with isolates possessing the mosaic penA-34.001, in combination with an mtrR promoter A deletion, and PorB1b amino acid substitutions G120K/A121N. Phylogenetic analysis revealed two main clades of circulating strains, which were associated with the N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 and closely related STs, and characterized by a high prevalence rate, wide geographical distribution and temporal persistence.

CONCLUSIONS: N. gonorrhoeae isolates with decreased susceptibility and resistance to ESCs in Argentina have emerged and rapidly spread mainly due to two clonal expansions after importation of one or two strains, which are associated with the international MDR NG-MAST ST1407 clone. The identification of the geographical dissemination and characteristics of these predominant clones may help to focus action plans and public health policies to control the spread of ESC resistance in Argentina. Dual antimicrobial therapy (ceftriaxone plus azithromycin) for gonorrhoea needs to be considered in Argentina.

Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-72874 (URN)10.1093/jac/dkz054 (DOI)000482076800014 ()30820563 (PubMedID)2-s2.0-85066839578 (Scopus ID)
Note

Funding Agencies:

Programa de Becas de Formacion en el Exterior en Ciencia y Tecnologia (Grant Bec.Ar - CIT 2017), Argentina  

Örebro County Council Research Committee  

Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden 

Available from: 2019-03-04 Created: 2019-03-04 Last updated: 2019-11-12Bibliographically approved
Boiko, I., Golparian, D., Krynsytska, I. & Unemo, M. (2019). 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, Ukraine. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 127(9), 627-634
Open this publication in new window or tab >>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, Ukraine
2019 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 9, p. 627-634Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2019
Keywords
Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Aptima Combo 2 assay, Aptima Trichomonas vaginalis assay, Ukraine
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-74783 (URN)10.1111/apm.12975 (DOI)000481445100004 ()31225920 (PubMedID)2-s2.0-85070737441 (Scopus ID)
Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-11-15Bibliographically approved
Foerster, S., Drusano, G., Golparian, D., Neely, M., Piddock, L. J. V., Alirol, E. & Unemo, M. (2019). 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 gonorrhoeae. Journal of Antimicrobial Chemotherapy, 74(12), 3521-3529
Open this publication in new window or tab >>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 gonorrhoeae
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2019 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, no 12, p. 3521-3529Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-78560 (URN)10.1093/jac/dkz376 (DOI)000501732800016 ()31730160 (PubMedID)2-s2.0-85075070269 (Scopus ID)
Note

Funding Agencies:

Global Antibiotic Research & Development Partnership (GARDP)  

Örebro County Council Research Committee, Örebro, Sweden  

Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden 

Available from: 2019-12-13 Created: 2019-12-13 Last updated: 2020-01-14Bibliographically approved
Foerster, S., Drusano, G., Golparian, D., Neely, M., Piddock, L., Alirol, E. & Unemo, M. (2019). IN VITRO COMBINATION TESTING AND SELECTION OF RESISTANCE TO ZOLIFLODACIN COMBINED WITH SIX ANTIMICROBIALS FOR N. GONORRHOEAE. Sexually Transmitted Infections, 95(Suppl. 1), A50-A50
Open this publication in new window or tab >>IN VITRO COMBINATION TESTING AND SELECTION OF RESISTANCE TO ZOLIFLODACIN COMBINED WITH SIX ANTIMICROBIALS FOR N. GONORRHOEAE
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2019 (English)In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, no Suppl. 1, p. A50-A50Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-79390 (URN)10.1136/sextrans-2019-sti.135 (DOI)000506050100132 ()
Available from: 2020-01-27 Created: 2020-01-27 Last updated: 2020-01-27Bibliographically approved
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