title: Macrolide resistance and azithromycin failure in a Mycoplasma genitalium-infected cohort and response of azithromycin failures to alternative antibiotic regimens.
abstract: BACKGROUND
  Our aim was to determine the efficacy of 1 g azithromycin and alternative antibiotic regimens in a prospective cohort of Mycoplasma genitalium-infected participants, and factors associated with azithromycin failure.
  
  
  METHODS
  Consecutive eligible M. genitalium-infected men and women attending the Melbourne Sexual Health Centre between July 2012 and June 2013 were treated with 1 g of azithromycin and retested by polymerase chain reaction (PCR) on days 14 and 28. Cure was defined as PCR negative on day 28. Cases failing azithromycin were treated with moxifloxacin, and those failing moxifloxacin were treated with pristinamycin. Pre- and posttreatment samples were assessed for macrolide resistance mutations (MRMs) by high-resolution melt analysis. Mycoplasma genitalium samples from cases failing moxifloxacin were sequenced for fluoroquinolone resistance mutations. Multivariable analysis was used to examine associations with azithromycin failure.
  
  
  RESULTS
  Of 155 participants treated with 1 g azithromycin, 95 (61% [95% confidence interval {CI}, 53%-69%]) were cured. Pretreatment MRM was detected in 56 (36% [95% CI, 28%-43%]) participants, and strongly associated with treatment failure (87% [95% CI, 76%-94%]; adjusted odds ratio, 47.0 [95% CI, 17.1-129.0]). All 11 participants who had MRM detected in posttreatment samples failed azithromycin. Moxifloxacin was effective in 53(88% [95% CI, 78%-94%]) of 60 cases failing azithromycin; all failures had gyrA and parC mutations detected in pretreatment samples. Six of 7 patients failing moxifloxacin treatment received pristinamycin, and all were PCR negative 28 days after pristinamycin treatment.
  
  
  CONCLUSIONS
  We report a high azithromycin failure rate (39%) in an M. genitalium-infected cohort in association with high levels of pretreatment macrolide resistance. Moxifloxacin failure occurred in 12% of patients who received moxifloxacin; all had pretreatment fluoroquinolone mutations detected. Pristinamycin was highly effective in treating macrolide- and quinolone-resistant strains.
authors.affiliation: Melbourne Sexual Health Centre, Alfred Hospital Melbourne School of Population and Global Health.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bissessor
authors.affiliation: Department of Obstetrics and Gynaecology, University of Melbourne Department of Microbiology, Infectious Diseases, The Royal Women's Hospital, Murdoch Childrens Research Institute.
authors.forename: Sepehr N
authors.initials: SN
authors.lastname: Tabrizi
authors.affiliation: Department of Microbiology, Infectious Diseases, The Royal Women's Hospital, Murdoch Childrens Research Institute.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Twin
authors.affiliation: Department of Microbiology, Infectious Diseases, The Royal Women's Hospital, Murdoch Childrens Research Institute.
authors.forename: Houda
authors.initials: H
authors.lastname: Abdo
authors.affiliation: Melbourne Sexual Health Centre, Alfred Hospital Central Clinical School, Monash University, Melbourne, Victoria, Australia.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Fairley
authors.affiliation: Melbourne Sexual Health Centre, Alfred Hospital Central Clinical School, Monash University, Melbourne, Victoria, Australia.
authors.forename: Marcus Y
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Melbourne Sexual Health Centre, Alfred Hospital Melbourne School of Population and Global Health Department of Microbiology, Infectious Diseases, The Royal Women's Hospital, Murdoch Childrens Research Institute.
authors.forename: Lenka A
authors.initials: LA
authors.lastname: Vodstrcil
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Jorgen S
authors.initials: JS
authors.lastname: Jensen
authors.affiliation: Melbourne School of Population and Global Health.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Hocking
authors.affiliation: Department of Obstetrics and Gynaecology, University of Melbourne.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.affiliation: Melbourne Sexual Health Centre, Alfred Hospital Melbourne School of Population and Global Health Central Clinical School, Monash University, Melbourne, Victoria, Australia.
authors.forename: Catriona S
authors.initials: CS
authors.lastname: Bradshaw
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use; D006801:Humans; D018942:Macrolides / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D009175:Mycoplasma Infections / Q000188:drug therapy* / Q000382:microbiology; D045704:Mycoplasma genitalium / Q000187:drug effects* / Q000302:isolation & purification; D025762:Pristinamycin / Q000627:therapeutic use; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D018942:Macrolides; D025762:Pristinamycin; D017963:Azithromycin; D000077266:Moxifloxacin
keywords: Mycoplasma genitalium; azithromycin; macrolide resistance; moxifloxacin; pristinamycin