Researchers detected macrolide resistance mutations (MRMs) in more than 40 percent of Mycoplasma (M.) genitalium infections among individuals aged 14-59 years in the US in 2017-2018, representing about 1.4 million macrolide-resistant infections.
Macrolides are a class of antibiotics used to treat or prevent bacterial infections. They primarily work by inhibiting bacterial protein synthesis. Macrolide resistance occurs when bacteria develop the ability to survive exposure to macrolide antibiotics (such as azithromycin, clarithromycin, and erythromycin).
In the current study, the weighted MRM prevalence was 42.7 percent, corresponding to about 1.4 million macrolide-resistant M. genitalium infections. The most common mutation was A2058G, with a weighted prevalence of 26.9 per cent.
MRM prevalence was significantly higher among individuals <25 years than among those aged 25 years or older (64.3 percent vs 30.7 percent). It decreased by 5 percent for each 1-year increase in age (prevalence ratio [PR], 0.95, 95 percent confidence interval [CI], 0.92-0.98).
The highest MRM prevalence was observed among people who had received mental health care (92.9 percent; PR, 2.7, 95 percent CI, 1.53-5.12) or those who reported a new sexual partner in the past year (76.1 percent; PR, 2.7, 95 percent CI, 1.34–5.34).
No quinolone resistance-associated mutations (QRAMs) were found in any specimens tested. Specifically, none were detected in parC (0 of 41 specimens) or gyrA (0 of 42 specimens).
Population-level prevalence
Researchers analysed urine specimens from participants aged 14-59 years in the 2017-2018 National Health and Nutrition Examination Survey (NHANES) to estimate the population-level prevalence of antimicrobial resistance in M. genitalium. [Open Forum Infect Dis 2026;13:ofag641]
NHANES collected data from the civilian, non-institutionalised US population through clustered sampling, including household interviews and health examinations at mobile examination centres.
MRMs in the 23S rRNA gene were detected using reverse transcriptase polymerase chain reaction followed by PyroMark24 sequencing, whereas QRAMs in the parC and gyrA genes were detected using conventional polymerase chain reaction followed by Sanger sequencing.
Researchers estimated the overall weighted prevalence of MRMs and the prevalence ratios across sociodemographic, behavioural, and clinical subgroups.
Of 58 M. genitalium-positive urine specimens, 49 (84.5 percent) yielded MRM results, 41 (70.7 percent) yielded parC QRAM results, and 42 (72.4 percent) yielded gyrA QRAM results.
Implication to practice
“The high MRM prevalence likely resulted from the widespread use of macrolides,” said the researchers led by Dr Lisa Manhart of the Department of Epidemiology, School of Public Health, University of Washington in Seattle, Washington, US.
She added that although QRAMs were not detected, quinolone resistance has increased in other countries and will continue to increase in the US as M. genitalium testing and moxifloxacin treatment expand.
“MRM testing is becoming more widely available. Ideally, it should be done alongside diagnostic testing for M. genitalium, and moxifloxacin should be prescribed only if azithromycin is unsuitable,” she noted.
Study caveats included the small number of M. genitalium-positive specimens, which reduced statistical power and increased variance, particularly for population subgroup estimates that may be unstable. Some M. genitalium-positive participants lacked specimens, and testing of available specimens yielded no results. These factors may have introduced residual bias despite the use of weighted analysis.
The National Institute of Allergy and Infectious Diseases at the National Institutes of Health supported this study.