Mycoplasma genitalium: the next sexually transmitted superbug?

Mycoplasma genitalium is a common cause of nongonococcal urethritis. Treatment trials have shown that doxycycline is inefficient, whereas a 5-day course of azithromycin eradicates the bacterium from 95% of infected men. The aim of the study was to establish the reason for the occasional treatment failures. Seven M. genitalium strains isolated from men who experienced azithromycin treatment failure were tested for in vitro susceptibility to macrolides with use of a cell culture-based method. The genetic basis for the drug resistance was established by sequencing parts of the 23S ribosomal RNA gene and the genes encoding the L4 and L22 proteins. Nine sets of specimens obtained before and after treatment from patients who experienced azithromycin treatment failure were examined with use of sequencing of polymerase chain reaction products. The 7 strains that were isolated from patients who experienced treatment failure with azithromycin had minimum inhibitory concentrations >8 microg/mL for azithromycin and erythromycin. Three different mutations at positions 2058 and 2059 (Escherichia coli numbering) in region V of the 23S rRNA gene were found. Of the 9 patients with specimens obtained before and after treatment, only 2 had an initial specimen in which the mutation was present, indicating that drug resistance was induced as the result of an inappropriate dosage of azithromycin. Development of macrolide resistance was shown to correlate with subsequent azithromycin treatment failure. The genetic basis for the drug resistance was shown to be mutations in region V of the 23S rRNA gene, which is well described in other Mollicutes. These findings raise concern about the use of single-dose azithromycin treatment of nongonococcal urethritis of unknown etiology.

Background Mycoplasma genitalium is a common cause of non-gonococcal non-chlamydial urethritis and cervicitis. Testing of asymptomatic populations has been proposed, but prevalence in asymptomatic populations is not well established. We aimed to estimate the prevalence of M. genitalium in the general population, pregnant women, men who have sex with men (MSM), commercial sex workers (CSWs) and clinic-based samples. Methods We searched Embase, Medline, IndMED, African Index Medicus and LILACS from 1 January 1991 to 12 July 2016 without language restrictions. We included studies with 500 participants or more. Two reviewers independently screened and selected studies and extracted data. We examined forest plots and conducted random-effects meta-analysis to estimate prevalence, if appropriate. Between-study heterogeneity was examined using the I2 statistic and meta-regression. Results Of 3316 screened records, 63 were included. In randomly selected samples from the general population, the summary prevalence was 1.3% (95% CI 1.0% to 1.8%, I2 41.5%, three studies, 9091 people) in countries with higher levels of development and 3.9% (95% CI 2.2 to 6.7, I2 89.2%, three studies, 3809 people) in countries with lower levels. Prevalence was similar in women and men (P=0.47). In clinic based samples, prevalence estimates were higher, except in asymptomatic patients (0.8%, 95% CI 0.4 to 1.4, I2 0.0%, three studies, 2889 people). Summary prevalence estimates were, in the following groups: pregnant women 0.9% (95% CI 0.6% to 1.4%, I2 0%, four studies, 3472 people), MSM in the community 3.2% (95% CI 2.1 to 5.1, I2 78.3%, five studies, 3012 people) and female CSWs in the community 15.9% (95% CI 13.5 to 18.9, I2 79.9%, four studies, 4006 people). Discussion This systematic review can inform testing guidelines for M. genitalium. The low estimated prevalence of M. genitalium in the general population, pregnant women and asymptomatic attenders at clinics does not support expansion of testing to these groups. Registration numbers PROSPERO: CRD42015020420

Escalating resistance to azithromycin and moxifloxacin is being reported for Mycoplasma genitalium in the Asia-Pacific region. Analyzing 140 infections, we found pretreatment fluoroquinolone-resistance mutations in parC (13.6%) and gyrA (5%). ParC S83 changes were associated with moxifloxacin failure. Combined macrolide/fluoroquinolone-resistance mutations were in 8.6% of specimens, for which recommended therapies would be ineffective.