{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:36:01Z","timestamp":1792449361534,"version":"4.5.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Mycoplasma genitalium<\/jats:italic> (MG) is one of the most warning emerging sexually transmitted pathogens also due to its ability in developing resistance to antibiotics. MG causes different conditions ranging from asymptomatic infections to acute mucous inflammation. Resistance-guided therapy has demonstrated the best cure rates and macrolide resistance testing is recommended in many international guidelines. However, diagnostic and resistance testing can only be based on molecular methods, and the gap between genotypic resistance and microbiological clearance has not been fully evaluated yet. This study aims at finding mutations associated with MG antibiotic resistance and investigating the relationship with microbiological clearance amongst MSM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From 2017 to 2021, genital (urine) and extragenital (pharyngeal and anorectal swabs) biological specimens were provided by men-who-have-sex-with-men (MSM) attending the STI clinic of the Infectious Disease Unit at the Verona University Hospital, Verona, Italy. A total of 1040 MSM were evaluated and 107 samples from 96 subjects resulted positive for MG. Among the MG-positive samples, all those available for further analysis (n=47) were considered for detection of mutations known to be associated with macrolide and quinolone resistance. 23S rRNA, <jats:italic>gyrA<\/jats:italic> and <jats:italic>parC<\/jats:italic> genes were analyzed by Sanger sequencing and Allplex\u2122 MG and AziR Assay (Seegene).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 96\/1040 (9.2%) subjects tested positive for MG in at least one anatomical site. MG was detected in 107 specimens: 33 urine samples, 72 rectal swabs and 2 pharyngeal swabs. Among them, 47 samples from 42 MSM were available for investigating the presence of mutations associated with macrolide and quinolone resistance: 30\/47 (63.8%) showed mutations in 23S rRNA while 10\/47 (21.3%) in <jats:italic>parC<\/jats:italic> or <jats:italic>gyrA<\/jats:italic> genes. All patients with positive Test of Cure (ToC) after first-line treatment with azithromycin (n=15) were infected with 23S rRNA-mutated MG strains. All patients undergoing second-line moxifloxacin treatment (n=13) resulted negative at ToC, even those carrying MG strains with mutations in <jats:italic>parC<\/jats:italic> gene (n=6).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our observations confirm that mutations in 23S rRNA gene are associated with azithromycin treatment failure and that mutations in <jats:italic>parC<\/jats:italic> gene alone are not always associated with phenotypic resistance to moxifloxacin. This reinforces the importance of macrolide resistance testing to guide the treatment and reduce antibiotic pressure on MG strains.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1155451","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T08:47:05Z","timestamp":1680252425000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Mycoplasma genitalium antibiotic resistance-associated mutations in genital and extragenital samples from men-who-have-sex-with-men attending a STI clinic in Verona, Italy"],"prefix":"10.3389","volume":"13","author":[{"given":"Angela","family":"Sandri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Carelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Visentin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Savoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gelinda","family":"De Grandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Mirandola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Lleo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Signoretto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Cordioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"B36","doi-asserted-by":"publisher","first-page":"dlab091","DOI":"10.1093\/jacamr\/dia091","article-title":"High prevalence of circulating dual-class resistant mycoplasma genitalium in asymptomatic MSM in Tokyo, Japan","volume":"3","author":"Ando","year":"2021","journal-title":"JAC Antimicrob. Resist."},{"key":"B27","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1007\/s10096-020-04068-3","article-title":"Multi-year prevalence and macrolide resistance of mycoplasma genitalium in clinical samples from a southern Italian hospital","volume":"40","author":"Angela","year":"2021","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis. Off Publ. Eur. Soc. Clin. Microbiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1128\/JCM.42.1.203-211.2004","article-title":"Diagnostic assessment of mycoplasma genitalium in culture-positive women","volume":"42","author":"Baseman","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e2127","DOI":"10.1093\/cid\/ciaa1832","article-title":"High prevalence and high rate of antibiotic resistance of mycoplasma genitalium infections in men who have sex with men: A substudy of the ANRS IPERGAY pre-exposure prophylaxis trial","volume":"73","author":"Ber\u00e7ot","year":"2021","journal-title":"Clin. Infect. Dis. Off Publ. Infect. Dis. Soc. Am."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1093\/cid\/ciu1162","article-title":"Macrolide resistance and azithromycin failure in a mycoplasma genitalium-infected cohort and response of azithromycin failures to alternative antibiotic regimens","volume":"60","author":"Bissessor","year":"2015","journal-title":"Clin. Infect. Dis. Off Publ. Infect. Dis. Soc. Am."},{"key":"B1","doi-asserted-by":"publisher","first-page":"E61","DOI":"10.1111\/j.1749-6632.2011.06418.x","article-title":"The evolution of mycoplasma genitalium","volume":"1230","author":"Blanchard","year":"2011","journal-title":"Ann. N Y Acad. Sci."},{"key":"B28","doi-asserted-by":"publisher","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":"B30","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s12879-021-05801-9","article-title":"Prevalence of urogenital, anal, and pharyngeal infections with chlamydia trachomatis, neisseria gonorrhoeae, and mycoplasma genitalium: A cross-sectional study in reunion island","volume":"21","author":"Calas","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"001429","DOI":"10.1099\/jmm.0.001429","article-title":"Prevalence of mycoplasma genitalium fluoroquinolone-resistance markers, and dual-class-resistance markers, in asymptomatic men who have sex with men","volume":"70","author":"Chua","year":"2021","journal-title":"J. Med. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","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":"B23","doi-asserted-by":"publisher","first-page":"962","DOI":"10.3390\/antibiotics10080962","article-title":"Antibiotic resistance and genotypes of mycoplasma genitalium during a resistance-guided treatment regime in a German university hospital","volume":"10","author":"Dumke","year":"2021","journal-title":"Antibiot. Basel Switz."},{"key":"B34","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.eimc.2018.04.008","article-title":"Mycoplasma genitalium and antibiotic resistance in spain; the need for an effective response against an emerging problem","volume":"37","author":"Fern\u00e1ndez-Huerta","year":"2019","journal-title":"Enfermedades Infecc. Microbiol. Clin. Engl. Ed."},{"key":"B43","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1097\/OLQ.0000000000001493","article-title":"Frequency and correlates of mycoplasma genitalium antimicrobial resistance mutations and their association with treatment outcomes: Findings from a national sentinel surveillance pilot in England","volume":"48","author":"Fifer","year":"2021","journal-title":"Sex Transm. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1186\/s12864-017-4399-6","article-title":"Mycoplasma genitalium: whole genome sequence analysis, recombination and population structure","volume":"18","author":"Fookes","year":"2017","journal-title":"BMC Genomics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"S406","DOI":"10.1093\/infdis\/jix104","article-title":"Mycoplasma genitalium: Accurate diagnosis is necessary for adequate treatment","author":"Gaydos","year":"2017","journal-title":"J. Infect. Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1099\/mic.0.000830","article-title":"Mycoplasma genitalium: A review","volume":"166","author":"Gnanadurai","year":"2020","journal-title":"Microbiol. Read Engl."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.3390\/microorganisms10081587","article-title":"Molecular typing reveals distinct mycoplasma genitalium transmission networks among a cohort of men who have sex with men and a cohort of women in France","volume":"10","author":"Guiraud","year":"2022","journal-title":"Microorganisms"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e0198355","DOI":"10.1371\/journal.pone.0198355","article-title":"Mutations in ParC and GyrA of moxifloxacin-resistant and susceptible mycoplasma genitalium strains","volume":"13","author":"Hamasuna","year":"2018","journal-title":"PloS One"},{"key":"B10","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1128\/JCM.02056-06","article-title":"Isolation of mycoplasma genitalium from first-void urine specimens by coculture with vero cells","volume":"45","author":"Hamasuna","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1177\/0956462421999287","article-title":"High prevalence and resistance rates of mycoplasma genitalium among patients visiting two sexually transmitted infection clinics in the Netherlands","volume":"32","author":"Hetem","year":"2021","journal-title":"Int. J. STD AIDS."},{"key":"B13","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1186\/s12879-015.1041-6","article-title":"Management of mycoplasma genitalium infections - can we hit a moving target","volume":"15","author":"Jensen","year":"2015","journal-title":"BMC Infect. Dis."},{"key":"B25","doi-asserted-by":"publisher","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. JEADV"},{"key":"B6","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/jdv.17972","article-title":"2021 European Guideline on the management of mycoplasma genitalium infections","volume":"36","author":"Jensen","year":"2022","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"B33","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1136\/sextrans-2019-054058","article-title":"Extragenital mycoplasma genitalium infections among men who have sex with men","volume":"96","author":"Latimer","year":"2020","journal-title":"Sex Transm. Infect."},{"key":"B4","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1093\/cid\/civ312","article-title":"Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis","volume":"61","author":"Lis","year":"2015","journal-title":"Clin. Infect. Dis. Off Publ. Infect. Dis. Soc. Am."},{"key":"B20","doi-asserted-by":"publisher","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":"B39","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1093\/infdis\/jiz550","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":"B46","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00278-22","article-title":"parC variants in mycoplasma genitalium: Trends over time and association with moxifloxacin failure","volume":"66","author":"Murray","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"B41","doi-asserted-by":"publisher","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":"B47","doi-asserted-by":"publisher","first-page":"ciad057","DOI":"10.1093\/cid\/ciad057","article-title":"gyrA mutations in mycoplasma genitalium and their contribution to moxifloxacin failure: Time for the next generation of resistance-guided therapy","author":"Murray","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1177\/09564624211030040","article-title":"Mycoplasma genitalium infection in women reporting dysuria: A pilot study and review of the literature","volume":"32","author":"Olson","year":"2021","journal-title":"Int. J. STD AIDS."},{"key":"B32","doi-asserted-by":"publisher","first-page":"100779","DOI":"10.1016\/j.eclinm.2021.100779","article-title":"Impact of screening on the prevalence and incidence of mycoplasma genitalium and its macrolide resistance in men who have sex with men living in Australia: A mathematical model","volume":"33","author":"Ong","year":"2021","journal-title":"E. Clin. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.pharmthera.2014.03.003","article-title":"Azithromycin: Mechanisms of action and their relevance for clinical applications","volume":"143","author":"Parnham","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1136\/sextrans-2017-053164","article-title":"Detection of markers predictive of macrolide and fluoroquinolone resistance in mycoplasma genitalium from patients attending sexual health services in England","volume":"94","author":"Pitt","year":"2018","journal-title":"Sex Transm. Infect."},{"key":"B45","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1136\/sextrans-2019-054129","article-title":"Antimicrobial resistance in mycoplasma genitalium sampled from the British general population","volume":"96","author":"Pitt","year":"2020","journal-title":"Sex Transm. Infect."},{"key":"B21","doi-asserted-by":"publisher","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":"B8","doi-asserted-by":"publisher","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":"B29","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1071\/SH12092","article-title":"Anatomic distribution of neisseria gonorrhoeae, chlamydia trachomatis and mycoplasma genitalium infections in men who have sex with men","volume":"10","author":"Reinton","year":"2013","journal-title":"Sex Health"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e0236921","DOI":"10.1128\/jcm.02369-21","article-title":"Clinical importance of superior sensitivity of the aptima TMA-based assays for mycoplasma genitalium detection","volume":"60","author":"Salado-Rasmussen","year":"2022","journal-title":"J. Clin. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s002030050339","article-title":"Tetracyclines: Antibiotic action, uptake, and resistance mechanisms","volume":"165","author":"Schnappinger","year":"1996","journal-title":"Arch. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"461","DOI":"10.2340\/00015555-0929","article-title":"Guidelines for the laboratory diagnosis of mycoplasma genitalium infections in East European countries","volume":"90","author":"Shipitsyna","year":"2010","journal-title":"Acta Derm. Venereol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.3201\/eid2311.170998","article-title":"Mycoplasma genitalium infection in adults reporting sexual contact with infected partners, Australia, 2008-2016","volume":"23","author":"Slifirski","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1136\/sextrans-2018-053831","article-title":"Launch of the BASHH guideline for the management of M. genitalium in adults","volume":"95","author":"Soni","year":"2019","journal-title":"Sex Transm. Infect."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e267","DOI":"10.1016\/S1473-3099(21)00629-0","article-title":"Individualised treatment of mycoplasma genitalium infection-incorporation of fluoroquinolone resistance testing into clinical care","volume":"22","author":"Sweeney","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"105911","DOI":"10.1016\/j.ijantimicag.2020.105911","article-title":"Molecular basis of antimicrobial resistance in mycoplasma genitalium","volume":"55","author":"van der Schalk","year":"2020","journal-title":"Int. J. Antimicrob. Agents."},{"key":"B37","doi-asserted-by":"publisher","first-page":"332","DOI":"10.3201\/eid2602.190533","article-title":"Mycoplasma genitalium antimicrobial resistance in community and sexual health clinic patients, Auckland, new Zealand","volume":"26","author":"Vesty","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"B31","doi-asserted-by":"publisher","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. Morb. Mortal. Wkly. Rep. Recomm. Rep."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1155451\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T08:47:11Z","timestamp":1680252431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1155451\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":47,"alternative-id":["10.3389\/fcimb.2023.1155451"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1155451","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,31]]},"article-number":"1155451"}}