{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T07:47:16Z","timestamp":1794037636785,"version":"4.8.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Australian NHMRC Leadership Investigator Grants","award":["GNT1172900"],"award-info":[{"award-number":["GNT1172900"]}]},{"name":"Australian NHMRC Leadership Investigator Grants","award":["GNT1173361"],"award-info":[{"award-number":["GNT1173361"]}]},{"name":"Australian NHMRC Emerging Leadership Investigator Grants","award":["GNT1172873"],"award-info":[{"award-number":["GNT1172873"]}]},{"name":"Australian NHMRC Emerging Leadership Investigator Grants","award":["GNT1174555"],"award-info":[{"award-number":["GNT1174555"]}]},{"name":"Australian Research Council (ARC) Industrial Transformation Research Hub Grant","award":["IH190100021"],"award-info":[{"award-number":["IH190100021"]}]},{"name":"Victorian Medical Research Acceleration Fund grant"},{"name":"Queensland Advancing Clinical Research Fellowship"},{"DOI":"10.13039\/501100003550","name":"Queensland Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003550","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Mycoplasma genitalium (MG) infection is challenging to cure because of rising antimicrobial resistance and limited treatment options.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a prospective evaluation of the efficacy and tolerability of resistance-guided combination antimicrobial therapy for MG treatment at Melbourne Sexual Health Centre (August 2019\u2013December 2020). All patients received 7 days of doxycycline before combination therapy based on the macrolide-resistant profile. Macrolide-susceptible infections received combination doxycycline\u2005+\u2005azithromycin (1\u00a0g, day 1; 500\u00a0mg, days 2\u20134) and macrolide-resistant infections combination doxycycline\u2005+\u2005moxifloxacin (400\u00a0mg daily for 7 days). Adherence and adverse effects were recorded at test-of-cure, recommended 14\u201328 days after antimicrobial completion. Sequencing was performed to determine the prevalence of single nucleotide polymorphisms (SNPs) in the parC gene and their association with moxifloxacin treatment outcomes in macrolide-resistant infections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 100 patients with macrolide-susceptible MG treated with doxycycline\u2005+\u2005azithromycin, 93 were cured (93.0%; 95% confidence interval [CI], 86.1\u201397.1). Of 247 patients with macrolide-resistant MG receiving doxycycline\u2005+\u2005moxifloxacin, 210 were cured (85.0%; 95% CI, 80.0\u201389.2). parC sequencing was available for 164 (66%) macrolide-resistant infections; 29% had SNPs at parC S83 or D87 (23% S83I). The absence of SNPs at parC S83\/D87 was associated with 98.3% cure (95% CI, 93.9\u201399.8) following doxycycline\u2005+\u2005moxifloxacin. The presence of the parC S83I-SNP was associated with failure in 62.5% (95% CI, 45.8\u201377.3). Side effects were common (40%\u201346%) and predominantly mild and gastrointestinal.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Combination doxycycline\u2005+\u2005azithromycin achieved high cure for macrolide-susceptible infections. However, in the context of a high prevalence of the parC S83I mutation (23%) in macrolide-resistant infections, doxycycline\u2005+\u2005moxifloxacin cured only 85%. Infections that were wild-type for S83\/D87 experienced high cure following doxycycline\u2005+\u2005moxifloxacin, supporting the use of a parC-resistance\/susceptibility testing strategy in clinical care.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciab1058","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T12:09:07Z","timestamp":1641298147000},"page":"813-823","source":"Crossref","is-referenced-by-count":54,"title":["Combination Therapy for <i>Mycoplasma genitalium<\/i>, and New Insights Into the Utility of <i>parC<\/i> Mutant Detection to Improve Cure"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3679-9195","authenticated-orcid":false,"given":"Lenka A","family":"Vodstrcil","sequence":"first","affiliation":[{"name":"Melbourne Sexual Health Centre, Alfred Health , Carlton, Victoria , Australia"},{"name":"Central Clinical School, Monash University , Melbourne, Victoria , Australia"},{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica L","family":"Plummer","sequence":"additional","affiliation":[{"name":"Melbourne Sexual Health Centre, Alfred Health , Carlton, Victoria , Australia"},{"name":"Central Clinical School, Monash University , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Doyle","sequence":"additional","affiliation":[{"name":"Melbourne Sexual Health Centre, Alfred Health , Carlton, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald L","family":"Murray","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute , Parkville, Victoria , Australia"},{"name":"Women\u2019s Centre for Infectious Diseases, The Royal Women\u2019s Hospital , Parkville, Victoria , Australia"},{"name":"Department of Obstetrics and Gynaecology, The University of Melbourne , Parkville, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaveesha","family":"Bodiyabadu","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute , Parkville, Victoria , Australia"},{"name":"Women\u2019s Centre for Infectious Diseases, The Royal Women\u2019s Hospital , Parkville, Victoria , Australia"},{"name":"Department of Obstetrics and Gynaecology, The University of Melbourne , Parkville, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorgen S","family":"Jensen","sequence":"additional","affiliation":[{"name":"Research Unit for Reproductive Microbiology, Statens Serum Institut , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Whiley","sequence":"additional","affiliation":[{"name":"The University of Queensland Centre for Clinical Research (UQ-CCR) , Queensland , Australia"},{"name":"Pathology Queensland Central Laboratory , Queensland , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Sweeney","sequence":"additional","affiliation":[{"name":"The University of Queensland Centre for Clinical Research (UQ-CCR) , Queensland , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Royal Melbourne Hospital , Melbourne , Australia and"},{"name":"Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P F","family":"Chow","sequence":"additional","affiliation":[{"name":"Melbourne Sexual Health Centre, Alfred Health , Carlton, Victoria , Australia"},{"name":"Central Clinical School, Monash University , Melbourne, Victoria , Australia"},{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K","family":"Fairley","sequence":"additional","affiliation":[{"name":"Melbourne Sexual Health Centre, Alfred Health , Carlton, Victoria , Australia"},{"name":"Central Clinical School, Monash University , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona S","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Melbourne Sexual Health Centre, Alfred Health , Carlton, Victoria , Australia"},{"name":"Central Clinical School, Monash University , Melbourne, Victoria , Australia"},{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"2022091519081415200_CIT0001","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3201\/eid2305.161745","article-title":"Increasing macrolide and fluoroquinolone resistance in mycoplasma genitalium.","volume":"23","author":"Murray","year":"2017","journal-title":"Emerg Infect Dis"},{"key":"2022091519081415200_CIT0002","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/S1473-3099(20)30154-7","article-title":"Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis.","volume":"20","author":"Machalek","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2022091519081415200_CIT0003","doi-asserted-by":"crossref","first-page":"719","DOI":"10.3201\/eid2504.181258","article-title":"Symptoms, sites, and significance of mycoplasma genitalium in men who have sex with men.","volume":"25","author":"Read","year":"2019","journal-title":"Emerg Infect Dis"},{"key":"2022091519081415200_CIT0004","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1136\/sextrans-2017-053480","article-title":"Mycoplasma genitalium: high prevalence of resistance to macrolides and frequent anorectal infection in men who have sex with men in western Sydney.","volume":"94","author":"Couldwell","year":"2018","journal-title":"Sex Transm Infect"},{"key":"2022091519081415200_CIT0005","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1071\/SH18221","article-title":"Prevalence of rectal Mycoplasma genitalium and macrolide resistance in men who have sex with men attending Sydney sexual health centre.","volume":"17","author":"Bradley","year":"2020","journal-title":"Sex Health"},{"key":"2022091519081415200_CIT0006","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1111\/jdv.13849","article-title":"2016 European guideline on Mycoplasma genitalium infections.","volume":"30","author":"Jensen","year":"2016","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2022091519081415200_CIT0007","author":"Australian STI management guidelines."},{"key":"2022091519081415200_CIT0008","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1177\/0956462419825948","article-title":"British Association for Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium (2018).","volume":"30","author":"Soni","year":"2019","journal-title":"Int J STD AIDS"},{"key":"2022091519081415200_CIT0009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7004a1","article-title":"Sexually transmitted infections treatment guidelines, 2021.","volume":"70","author":"Workowski","year":"2021","journal-title":"MMWR Recomm Rep"},{"key":"2022091519081415200_CIT0010","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1093\/jac\/48.5.742","article-title":"Analysis of the gyrA and parC genes of Mycoplasma genitalium detected in first-pass urine of men with non-gonococcal urethritis before and after fluoroquinolone treatment.","volume":"48","author":"Deguchi","year":"2001","journal-title":"J Antimicrob Chemother"},{"key":"2022091519081415200_CIT0011","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1177\/0956462413502008","article-title":"Failure of moxifloxacin treatment in Mycoplasma genitalium infections due to macrolide and fluoroquinolone resistance.","volume":"24","author":"Couldwell","year":"2013","journal-title":"Int J STD AIDS"},{"key":"2022091519081415200_CIT0012","first-page":"1017","article-title":"Moxifloxacin and sitafloxacin treatment failure in mycoplasma genitalium infection: association with parC mutation G248T (S83I) and concurrent gyrA mutations.","volume":"221","author":"Murray","year":"2020","journal-title":"J Infect Dis"},{"key":"2022091519081415200_CIT0013","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1093\/cid\/ciz1031","article-title":"Resistance-guided antimicrobial therapy using doxycycline-moxifloxacin and doxycycline-2.5g azithromycin for the treatment of Mycoplasma genitalium infection: efficacy and tolerability.","volume":"71","author":"Durukan","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2022091519081415200_CIT0014","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1093\/cid\/ciy477","article-title":"Outcomes of resistance-guided sequential treatment of mycoplasma genitalium infections: a prospective evaluation.","volume":"68","author":"Read","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2022091519081415200_CIT0015","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.cell.2012.02.021","article-title":"Outwitting evolution: fighting drug-resistant TB, malaria, and HIV.","volume":"148","author":"Goldberg","year":"2012","journal-title":"Cell"},{"key":"2022091519081415200_CIT0016","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1128\/JCM.02312-16","article-title":"Prospective evaluation of resistance plus MG, a new multiplex quantitative PCR assay for detection of mycoplasma genitalium and macrolide resistance.","volume":"55","author":"Tabrizi","year":"2017","journal-title":"J Clin Microbiol"},{"key":"2022091519081415200_CIT0017","doi-asserted-by":"crossref","first-page":"106089","DOI":"10.1016\/j.mimet.2020.106089","article-title":"A custom amplicon sequencing approach to detect resistance associated mutations and sequence types in Mycoplasma genitalium.","volume":"179","author":"Plummer","year":"2020","journal-title":"J Microbiol Methods"},{"key":"2022091519081415200_CIT0018","doi-asserted-by":"crossref","first-page":"e02380","DOI":"10.1128\/AAC.02380-17","article-title":"In vitro activity of lefamulin against sexually transmitted bacterial pathogens..","volume":"62","author":"Paukner","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2022091519081415200_CIT0019","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/jac\/dky022","article-title":"In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant, fluoroquinolone-resistant and antimicrobial-susceptible Mycoplasma genitalium strains.","volume":"73","author":"Damiao Gouveia","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2022091519081415200_CIT0020","doi-asserted-by":"crossref","first-page":"328","DOI":"10.3201\/eid2402.170902","article-title":"Use of pristinamycin for macrolide-resistant mycoplasma genitalium infection.","volume":"24","author":"Read","year":"2018","journal-title":"Emerg Infect Dis"},{"key":"2022091519081415200_CIT0021","doi-asserted-by":"crossref","first-page":"ofaa291","DOI":"10.1093\/ofid\/ofaa291","article-title":"Nonquinolone options for the treatment of mycoplasma genitalium in the era of increased resistance.","volume":"7","author":"Doyle","year":"2020","journal-title":"Open Forum Infect Dis"},{"key":"2022091519081415200_CIT0022","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.3201\/eid2608.191806","article-title":"Doxycycline and sitafloxacin combination therapy for treating highly resistant mycoplasma genitalium.","volume":"26","author":"Durukan","year":"2020","journal-title":"Emerg Infect Dis"},{"key":"2022091519081415200_CIT0023","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1086\/599033","article-title":"A randomized comparison of azithromycin and doxycycline for the treatment of Mycoplasma genitalium-positive urethritis in men.","volume":"48","author":"Mena","year":"2009","journal-title":"Clin Infect Dis"},{"key":"2022091519081415200_CIT0024","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/cid\/ciq074","article-title":"Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens--a randomized clinical trial.","volume":"52","author":"Schwebke","year":"2011","journal-title":"Clin Infect Dis"},{"key":"2022091519081415200_CIT0025","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1093\/cid\/cis1022","article-title":"Standard treatment regimens for nongonococcal urethritis have similar but declining cure rates: a randomized controlled trial.","volume":"56","author":"Manhart","year":"2013","journal-title":"Clin Infect Dis"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciab1058\/42493552\/ciab1058.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/75\/5\/813\/45878120\/ciab1058.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/75\/5\/813\/45878120\/ciab1058.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T19:09:28Z","timestamp":1663268968000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/75\/5\/813\/6497514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":25,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,1,4]]},"published-print":{"date-parts":[[2022,9,14]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciab1058","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9,1]]},"published":{"date-parts":[[2022,1,4]]}}}