1887

Abstract

Failure of fluoroquinolones, the principal treatment option for macrolide-resistant infections, has recently emerged. This is of particular concern for men who have sex with men (MSM), who have high proportions of macrolide-resistant infections. Treatment failure with moxifloxacin is likely the result of single nucleotide polymorphisms (SNPs) in , whilst concurrent mutations may play a role.

The levels of fluoroquinolone resistance and dual-class (i.e. macrolide and fluoroquinolone) resistance in among asymptomatic MSM is unknown.

To (i) determine the proportion of fluoroquinolone resistance and dual-class resistance in infections among asymptomatic MSM, (ii) explore any clinical and behavioural associations with fluoroquinolone resistance, and (iii) determine the distribution of antibiotic resistance among sequence types (STs).

positive samples (=94) were obtained from 1001 asymptomatic MSM enrolled in a study at Melbourne Sexual Health Centre (Carlton, Australia) between August 2016 and September 2017. Sanger sequencing was performed to determine the proportion of infections with SNPs in that have previously been associated with failure of moxifloxacin (corresponding to amino changes S83I, D83R, D87Y and D87N) and in (corresponding to amino acid changes M95I, D99N, D99Y and D99G). Associations between clinical/behavioural factors and SNPs were examined. Strain typing was performed by sequencing a portion of the gene.

The proportion of MSM with infections harbouring and SNPs was 13.0 % [95 % confidence interval (CI): 6.8–23.2 %] and 4.7 % (95 % CI: 1.1–13.4 %), respectively; dual-class resistance was 13.0 %. No significant clinical/behavioural associations were found. Antibiotic resistance was not restricted to specific STs.

One in eight (13 %) of asymptomatic MSM with had an infection with dual-class-resistance mutations. Typing by sequence suggested fluoroquinolone resistance is arising from independent mutation events. This study illustrates that asymptomatic MSM may act as a reservoir for antibiotic-resistant .

Funding
This study was supported by the:
  • department of health and human services, state government of victoria
    • Principle Award Recipient: GeraldL Murray
  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001429
2021-09-30
2024-12-07
Loading full text...

Full text loading...

/deliver/fulltext/jmm/70/9/jmm001429.html?itemId=/content/journal/jmm/10.1099/jmm.0.001429&mimeType=html&fmt=ahah

References

  1. Taylor-Robinson D, Jensen JS. Mycoplasma genitalium: from chrysalis to multicolored butterfly. Clin Microbiol Rev 2011; 24:498–514 [View Article] [PubMed]
    [Google Scholar]
  2. Horner PJ, Martin DH. Mycoplasma genitalium infection in men. J Infect Dis 2017; 216:S396–S405 [View Article] [PubMed]
    [Google Scholar]
  3. Lis R, Rowhani-Rahbar A, Manhart LE. Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. Clin Infect Dis 2015; 61:418–426 [View Article] [PubMed]
    [Google Scholar]
  4. Ross JD, Brown L, Saunders P, Alexander S. Mycoplasma genitalium in asymptomatic patients: implications for screening. Sex Transm Infect 2009; 85:436–437 [View Article] [PubMed]
    [Google Scholar]
  5. Fernández-Huerta M, Barberá MJ, Esperalba J, Fernandez-Naval C, Vall-Mayans M et al. Prevalence of Mycoplasma genitalium and macrolide resistance among asymptomatic people visiting a point of care service for rapid STI screening: a cross-sectional study. Sex Transm Infect 2020; 96:300–305 [View Article] [PubMed]
    [Google Scholar]
  6. Berçot B, Charreau I, Rousseau C, Delaugerre C, Chidiac C et al. 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. Clin Infect Dis 2020ciaa1832 [View Article] [PubMed]
    [Google Scholar]
  7. Read TRH, Murray GL, Danielewski JA, Fairley CK, Doyle M et al. Symptoms, sites, and significance of Mycoplasma genitalium in men who have sex with men. Emerg Infect Dis 2019; 25:719–727 [View Article] [PubMed]
    [Google Scholar]
  8. Bradshaw CS, Fairley CK, Lister NA, Chen SJ, Garland SM et al. Mycoplasma genitalium in men who have sex with men at male-only saunas. Sex Transm Infect 2009; 85:432–435 [View Article] [PubMed]
    [Google Scholar]
  9. Francis SC, Kent CK, Klausner JD, Rauch L, Kohn R et al. Prevalence of rectal Trichomonas vaginalis and Mycoplasma genitalium in male patients at the San Francisco STD clinic, 2005-2006. Sex Transm Dis 2008; 35:797–800 [View Article] [PubMed]
    [Google Scholar]
  10. Soni S, Alexander S, Verlander N, Saunders P, Richardson D et al. The prevalence of urethral and rectal Mycoplasma genitalium and its associations in men who have sex with men attending a genitourinary medicine clinic. Sex Transm Infect 2010; 86:21–24 [View Article] [PubMed]
    [Google Scholar]
  11. Zheng B, Yin Y, Han Y, Shi M, Jian N et al. The prevalence of urethral and rectal Mycoplasma genitalium among men who have sex with men in China, a cross-sectional study. BMC Public Health 2014; 14:195 [View Article] [PubMed]
    [Google Scholar]
  12. Couldwell DL, Jalocon D, Power M, Jeoffreys NJ, Chen SCA et al. Mycoplasma genitalium: high prevalence of resistance to macrolides and frequent anorectal infection in men who have sex with men in western Sydney. Sex Transm Infect 2018; 94:406–410 [View Article] [PubMed]
    [Google Scholar]
  13. Crowell TA, Lawlor J, Lombardi K, Nowak RG, Hardick J et al. Anorectal and urogenital Mycoplasma genitalium in Nigerian men who have sex with men and transgender women: prevalence, incidence, and association with HIV. Sex Transm Dis 2020; 47:202–206 [View Article] [PubMed]
    [Google Scholar]
  14. Latimer RL, Shilling HS, Vodstrcil LA, Machalek DA, Fairley CK et al. Prevalence of Mycoplasma genitalium by anatomical site in men who have sex with men: a systematic review and meta-analysis. Sex Transm Infect 2020; 96:563–570 [View Article] [PubMed]
    [Google Scholar]
  15. Bradley I, Varma R, Knight V, Iliakis D, McNally L et al. Prevalence of rectal Mycoplasma genitalium and macrolide resistance in men who have sex with men attending Sydney Sexual Health Centre. Sex Health 2020; 17:114–120 [View Article] [PubMed]
    [Google Scholar]
  16. Bissessor M, Tabrizi SN, Bradshaw CS, Fairley CK, Hocking JS et al. The contribution of Mycoplasma genitalium to the aetiology of sexually acquired infectious proctitis in men who have sex with men. Clin Microbiol Infect 2016; 22:260–265 [View Article] [PubMed]
    [Google Scholar]
  17. Ong JJ, Aung E, Read TRH, Fairley CK, Garland SM et al. Clinical characteristics of anorectal Mycoplasma genitalium infection and microbial cure in men who have sex with men. Sex Transm Dis 2018; 45:522–526 [View Article] [PubMed]
    [Google Scholar]
  18. Machalek DA, Tao Y, Shilling H, Jensen JS, Unemo M et al. Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis. Lancet Infect Dis 2020; 20:1302–1314 [View Article] [PubMed]
    [Google Scholar]
  19. Kenyon C, Manoharan-Basil SS. Macrolide consumption and resistance in Mycoplasma genitalium. Lancet Infect Dis 2020; 20:1235–1236 [View Article] [PubMed]
    [Google Scholar]
  20. Read TRH, Fairley CK, Murray GL, Jensen JS, Danielewski J et al. Outcomes of resistance-guided sequential treatment of Mycoplasma genitalium infections: a prospective evaluation. Clin Infect Dis 2019; 68:554–560 [View Article] [PubMed]
    [Google Scholar]
  21. Durukan D, Read TRH, Murray G, Doyle M, Chow EPF et al. Resistance-guided antimicrobial therapy using doxycycline-moxifloxacin and doxycycline-2.5g azithromycin for the treatment of Mycoplasma genitalium infection: efficacy and tolerability. Clin Infect Dis 2020; 71:1461–1468 [View Article] [PubMed]
    [Google Scholar]
  22. Li Y, Le WJ, Li S, Cao YP, Su XH. Meta-analysis of the efficacy of moxifloxacin in treating Mycoplasma genitalium infection. Int J STD AIDS 2017; 28:1106–1114 [View Article] [PubMed]
    [Google Scholar]
  23. Deguchi T, Maeda S, Tamaki M, Yoshida T, Ishiko H et al. 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. J Antimicrob Chemother 2001; 48:742–744 [View Article] [PubMed]
    [Google Scholar]
  24. Couldwell DL, Tagg KA, Jeoffreys NJ, Gilbert GL. Failure of moxifloxacin treatment in Mycoplasma genitalium infections due to macrolide and fluoroquinolone resistance. Int J STD AIDS 2013; 24:822–828 [View Article] [PubMed]
    [Google Scholar]
  25. Murray GL, Bradshaw CS, Bissessor M, Danielewski J, Garland SM et al. Increasing macrolide and fluoroquinolone resistance in Mycoplasma genitalium. Emerg Infect Dis 2017; 23:809–812 [View Article] [PubMed]
    [Google Scholar]
  26. Murray GL, Bodiyabadu K, Danielewski J, Garland SM, Machalek DA et al. Moxifloxacin and sitafloxacin treatment failure in Mycoplasma genitalium infection: association with parC mutation G248T (S83I) and concurrent gyrA mutations. J Infect Dis 2020; 221:1017–1024 [View Article] [PubMed]
    [Google Scholar]
  27. Australia Sexual Health Alliance Australian STI Management Guidelines for Use in Primary Care Sydney: Australia Sexual Health Alliance; 2018
    [Google Scholar]
  28. Golden MR, Workowski KA, Bolan G. Developing a public health response to Mycoplasma genitalium. J Infect Dis 2017; 216:S420–S426 [View Article]
    [Google Scholar]
  29. Bradshaw CS, Horner PJ, Jensen JS, White PJ. Syndromic management of STIs and the threat of untreatable Mycoplasma genitalium. Lancet Infect Dis 2018; 18:251–252 [View Article] [PubMed]
    [Google Scholar]
  30. Bradshaw CS, Jensen JS, Waites KB. New horizons in Mycoplasma genitalium treatment. J Infect Dis 2017; 216:S412–S419 [View Article]
    [Google Scholar]
  31. Baetselier D, Kenyon C, Vanden Berghe W, Smet H, Wouters K et al. An alarming high prevalence of resistance associated mutations to macrolides and fluoroquinolones in Mycoplasma genitalium in Belgium: results from samples collected between 2015-2018. Sex Transm Infect 2021; 97:297–303 [View Article] [PubMed]
    [Google Scholar]
  32. Shimada Y, Deguchi T, Nakane K, Masue T, Yasuda M et al. Emergence of clinical strains of Mycoplasma genitalium harbouring alterations in ParC associated with fluoroquinolone resistance. Int J Antimicrob Agents 2010; 36:255–258 [View Article] [PubMed]
    [Google Scholar]
  33. Hjorth SV, Björnelius E, Lidbrink P, Falk L, Dohn B et al. Sequence-based typing of Mycoplasma genitalium reveals sexual transmission. J Clin Microbiol 2006; 44:2078–2083 [View Article] [PubMed]
    [Google Scholar]
  34. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular Evolutionary Genetics Analysis across computing platforms. Mol Biol Evol 2018; 35:1547–1549 [View Article] [PubMed]
    [Google Scholar]
  35. Jalili V, Afgan E, Gu Q, Clements D, Blankenberg D et al. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2020 update. Nucleic Acids Res 2020; 48:W395–W402 [View Article] [PubMed]
    [Google Scholar]
  36. Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 2015; 32:268–274 [View Article] [PubMed]
    [Google Scholar]
  37. Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat Methods 2017; 14:587–589 [View Article] [PubMed]
    [Google Scholar]
  38. Letunic I, Bork P. Interactive Tree of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res 2019; 47:W256–W259 [View Article]
    [Google Scholar]
  39. Plummer EL, Murray GL, Bodiyabadu K, Su J, Garland SM et al. A custom amplicon sequencing approach to detect resistance associated mutations and sequence types in Mycoplasma genitalium. J Microbiol Methods 2020; 179:106089 [View Article] [PubMed]
    [Google Scholar]
  40. Piñeiro L, Idigoras P, Cilla G. Molecular typing of Mycoplasma genitalium-positive specimens discriminates between persistent and recurrent infections in cases of treatment failure and supports contact tracing. Microorganisms 2019; 7:609 [View Article]
    [Google Scholar]
  41. Fernández-Huerta M, Bodiyabadu K, Esperalba J, Bradshaw CS, Serra-Pladevall J et al. Multicenter clinical evaluation of a novel multiplex real-time PCR (qPCR) assay for detection of fluoroquinolone resistance in Mycoplasma genitalium. J Clin Microbiol 2019; 57:e00886–19 [View Article] [PubMed]
    [Google Scholar]
  42. Latimer RL, Vodstrcil L, Petra D, Fairley CK, Read TR et al. Extragenital Mycoplasma genitalium infections among men who have sex with men. Sex Transm Infect 2020; 96:10–18 [View Article] [PubMed]
    [Google Scholar]
  43. Romano SS, Jensen JS, Lowens MS, Morgan JL, Chambers LC et al. Long duration of asymptomatic Mycoplasma genitalium infection after syndromic treatment for nongonococcal urethritis. Clin Infect Dis 2019; 69:113–120 [View Article] [PubMed]
    [Google Scholar]
  44. Ong JJ, Ruan L, Lim AG, Bradshaw CS, Taylor-Robinson D et al. 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. EClinicalMedicine 2021; 33:100779 [View Article] [PubMed]
    [Google Scholar]
  45. Gaydos CA. Mycoplasma genitalium: accurate diagnosis is necessary for adequate treatment. J Infect Dis 2017; 216:S406–S411 [View Article]
    [Google Scholar]
  46. Bodiyabadu K, Danielewski J, Garland SM, Machalek DA, Bradshaw CS et al. Detection of parC gene mutations associated with quinolone resistance in Mycoplasma genitalium: evaluation of a multiplex real-time PCR assay. J Med Microbiol 2021; 70:001257 [View Article] [PubMed]
    [Google Scholar]
  47. Fernández-Huerta M, Serra-Pladevall J, Esperalba J, Moreno-Mingorance A, Fernández-Naval C et al. Single-locus-sequence-based typing of the mgpB gene reveals transmission dynamics in Mycoplasma genitalium. J Clin Microbiol 2020; 58:e01886–19 [View Article] [PubMed]
    [Google Scholar]
  48. Sweeney EL, Tickner J, Bletchly C, Nimmo GR, Whiley DM. Genotyping of Mycoplasma genitalium suggests de novo acquisition of antimicrobial resistance, Queensland, Australia. J Clin Microbiol 2020; 58:e00641–20 [View Article] [PubMed]
    [Google Scholar]
  49. Cazanave C, Charron A, Renaudin H, Bébéar C. Method comparison for molecular typing of French and Tunisian Mycoplasma genitalium-positive specimens. J Med Microbiol 2012; 61:500–506 [View Article] [PubMed]
    [Google Scholar]
  50. Guiraud J, Lounnas M, Boissière A, Le Roy C, Elguero E et al. Lower mgpB diversity in macrolide-resistant Mycoplasma genitalium infecting men visiting two sexually transmitted infection clinics in Montpellier, France. J Antimicrob Chemother 2021; 76:43–47 [View Article]
    [Google Scholar]
  51. Dumke R, Rust M, Glaunsinger T. MgpB types among Mycoplasma genitalium strains from men who have sex with men in Berlin, Germany, 2016-2018. Pathogens 2020; 9:12 [View Article]
    [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.001429
Loading
/content/journal/jmm/10.1099/jmm.0.001429
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error