Outcomes of Resistance-guided Sequential Treatment of Mycoplasma genitalium Infections: A Prospective Evaluation

Abstract

Background: Rising macrolide and quinolone resistance in Mycoplasma genitalium necessitate new treatment approaches. We evaluated outcomes of sequential antimicrobial therapy for M. genitalium guided by a macrolide-resistance assay.

Methods: In mid-2016, Melbourne Sexual Health Centre switched from azithromycin to doxycycline (100 mg twice daily for 7 days) for nongonococcal urethritis, cervicitis, and proctitis. Cases were tested for M. genitalium and macrolide-resistance mutations (MRMs) by polymerase chain reaction. Directly after doxycycline, MRM-negative infections received 2.5 g azithromycin (1 g, then 500 mg daily for 3 days), and MRM-positive infections received sitafloxacin (100 mg twice daily for 7 days). Assessment of test of cure and reinfection risk occurred 14-90 days after the second antibiotic.

Results: Of 244 evaluable M. genitalium infections (52 women, 68 heterosexual men, 124 men who have sex with men) diagnosed from 20 June 2016 to 15 May 2017, MRMs were detected in 167 (68.4% [95% confidence interval {CI}, 62.2%-74.2%]). Treatment with doxycycline decreased bacterial load by a mean 2.60 log10 (n = 56; P < .0001). Microbiologic cure occurred in 73 of 77 MRM-negative infections (94.8% [95% CI, 87.2%-98.6%]) and in 154 of 167 MRM-positive infections (92.2% [95% CI, 87.1%-95.8%]). Selection of macrolide resistance occurred in only 2 of 76 (2.6% [95% CI, .3%-9.2%]) macrolide-susceptible infections.

Conclusions: In the context of high levels of antimicrobial resistance, switching from azithromycin to doxycycline for presumptive treatment of M. genitalium, followed by resistance-guided therapy, cured ≥92% of infections, with infrequent selection of macrolide resistance.

Figure 1.

Selection of cases and outcomes of resistance-guided sequential treatment of Mycoplasma genitalium infections. Bottom row: data in parentheses indicate the 95% confidence interval. ^aReasons why 116 patients were not treated according to the resistance result and were excluded: women treated for pelvic inflammatory disease (n = 33), treatment initiated in the community (n = 23), patients given single-dose azithromycin at diagnosis, mostly with ceftriaxone for gonorrhea (n = 22), individuals who did not return for treatment (n = 16), patients given pristinamycin because quinolones were contraindicated (n = 12), other variations in dose or medication choice (n = 10). ^bThese individuals reported condomless sex with an untreated sexual partner. ^cSanger sequencing of pretreatment samples from these 4 individuals identified macrolide-resistance mutations (MRMs) in 1 sample. MRMs were detected in 2 of the remaining 3 samples, meaning MRMs emerged during treatment in 2 of 76 cases.

Figure 2.

Bacterial load (log₁₀) of Mycoplasma genitalium in urine samples before and after doxycycline 100 mg twice daily for 7 days (n = 56).