Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population

Background Mycoplasma genitalium is a common sexually transmitted infection. Treatment guidelines focus on those with symptoms and sexual contacts, generally with regimens including doxycycline and/or azithromycin as first-line and moxifloxacin as second-line treatment. We investigated the prevalence of antimicrobial resistance (AMR)-conferring mutations in M. genitalium among the sexually-active British general population. Methods The third national survey of sexual attitudes and lifestyles (Natsal-3) is a probability sample survey of 15 162 men and women aged 16–74 years in Britain conducted during 2010–12. Urine test results for M. genitalium were available for 4507 participants aged 16–44 years reporting >1 lifetime sexual partner. In this study, we sequenced regions of the 23S rRNA and parC genes to detect known genotypic determinants for resistance to macrolides and fluoroquinolones respectively. Results 94% (66/70) of specimens were re-confirmed as M. genitalium positive, with successful sequencing in 85% (56/66) for 23S rRNA and 92% (61/66) for parC genes. Mutations in 23S rRNA gene (position A2058/A2059) were detected in 16.1% (95%CI: 8.6% to 27.8%) and in parC (encoding ParC D87N/D87Y) in 3.3% (0.9%–11.2%). Macrolide resistance was more likely in participants reporting STI diagnoses (past 5 years) (44.4% (18.9%–73.3%) vs 10.6% (4.6%–22.6%); p=0.029) or sexual health clinic attendance (past year) (43.8% (23.1%–66.8%) vs 5.0% (1.4%–16.5%); p=0.001). All 11 participants with AMR-conferring mutations had attended sexual health clinics (past 5 years), but none reported recent symptoms. Conclusions This study highlights challenges in M. genitalium management and control. Macrolide resistance was present in one in six specimens from the general population in 2010–2012, but no participants with AMR M. genitalium reported symptoms. Given anticipated increases in diagnostic testing, new strategies including novel antimicrobials, AMR-guided therapy, and surveillance of AMR and treatment failure are recommended.

[1]  M. Rayment,et al.  British Association for Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium (2018) , 2019, International journal of STD & AIDS.

[2]  J. Jensen P664 In vitro evaluation of gepotidacin, an oral antimicrobial against multidrug-resistant mycoplasma genitalium , 2019, Poster Presentations.

[3]  S. Garland,et al.  Outcomes of Resistance-guided Sequential Treatment of Mycoplasma genitalium Infections: A Prospective Evaluation , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  J. Saunders,et al.  Mycoplasma genitalium: the next sexually transmitted superbug? , 2018, British Medical Journal.

[5]  C. Mercer,et al.  Collecting and exploiting data to understand a nation’s sexual health needs: Implications for the British National Surveys of Sexual Attitudes and Lifestyles (Natsal) , 2018, Sexually Transmitted Infections.

[6]  M. Unemo,et al.  In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant, fluoroquinolone-resistant and antimicrobial-susceptible Mycoplasma genitalium strains , 2018, The Journal of antimicrobial chemotherapy.

[7]  S. Paukner,et al.  In Vitro Activity of Lefamulin against Sexually Transmitted Bacterial Pathogens , 2018, Antimicrobial Agents and Chemotherapy.

[8]  N. Low,et al.  Prevalence of Mycoplasma genitalium in different population groups: systematic review andmeta-analysis , 2017, Sexually Transmitted Infections.

[9]  C. Mercer,et al.  Should we screen for the sexually-transmitted infection Mycoplasma genitalium? Evidence synthesis using a transmission-dynamic model , 2017, Scientific Reports.

[10]  N. Woodford,et al.  Detection of markers predictive of macrolide and fluoroquinolone resistance in Mycoplasma genitalium from patients attending sexual health services in England , 2017, Sexually Transmitted Infections.

[11]  I. Martin,et al.  Prevalence and antibiotic resistance of Mycoplasma genitalium among STI clinic attendees in Western Canada: a cross-sectional analysis , 2017, BMJ Open.

[12]  M. Cusini,et al.  2016 European guideline on Mycoplasma genitalium infections , 2016, Journal of the European Academy of Dermatology and Venereology.

[13]  D. Getman,et al.  Mycoplasma genitalium Prevalence, Coinfection, and Macrolide Antibiotic Resistance Frequency in a Multicenter Clinical Study Cohort in the United States , 2016, Journal of Clinical Microbiology.

[14]  V. Allen,et al.  Mycoplasma genitalium in Toronto, Ont: Estimates of prevalence and macrolide resistance. , 2016, Canadian family physician Medecin de famille canadien.

[15]  M. Cusini,et al.  European guideline on Mycoplasma genitalium infections , 2016 .

[16]  Anne M Johnson,et al.  Epidemiology of Mycoplasma genitalium in British men and women aged 16–44 years: evidence from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) , 2015, International journal of epidemiology.

[17]  K. Workowski,et al.  Sexually transmitted diseases treatment guidelines, 2015. , 2015, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[18]  A. Rowhani-Rahbar,et al.  Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. , 2015, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  M. Unemo,et al.  In Vitro Activity of the New Fluoroketolide Solithromycin (CEM-101) against Macrolide-Resistant and -Susceptible Mycoplasma genitalium Strains , 2014, Antimicrobial Agents and Chemotherapy.

[20]  A. Witney,et al.  High Prevalence of Antibiotic-Resistant Mycoplasma genitalium in Nongonococcal Urethritis: The Need for Routine Testing and the Inadequacy of Current Treatment Options , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  Anne M Johnson,et al.  Prevalence, risk factors, and uptake of interventions for sexually transmitted infections in Britain: findings from the National Surveys of Sexual Attitudes and Lifestyles (Natsal) , 2013, The Lancet.

[22]  Wendy Macdowall,et al.  Methodology of the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) , 2013, Sexually Transmitted Infections.

[23]  G. Gilbert,et al.  Fluoroquinolone and Macrolide Resistance-Associated Mutations in Mycoplasma genitalium , 2013, Journal of Clinical Microbiology.

[24]  M. Golden,et al.  Mycoplasma genitalium: should we treat and how? , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  D. Taylor-Robinson,et al.  Mycoplasma genitalium: from Chrysalis to Multicolored Butterfly , 2011, Clinical Microbiology Reviews.

[26]  D. Taylor-Robinson,et al.  Association of Mycoplasma genitalium with balanoposthitis in men with non-gonococcal urethritis , 2010, Sexually Transmitted Infections.

[27]  N. Verlander,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 , 2009, Sexually Transmitted Infections.

[28]  J. Hagood,et al.  Emerging Macrolide Resistance in Mycoplasma pneumoniae in Children: Detection and Characterization of Resistant Isolates , 2009, The Pediatric infectious disease journal.

[29]  J. Jensen,et al.  Use of TaqMan 5′ Nuclease Real-Time PCR for Quantitative Detection of Mycoplasma genitalium DNA in Males with and without Urethritis Who Were Attendees at a Sexually Transmitted Disease Clinic , 2004, Journal of Clinical Microbiology.

[30]  T. Deguchi,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. , 2001, The Journal of antimicrobial chemotherapy.