Treatment efficacy, treatment failures and selection of macrolide resistance in patients with high load of Mycoplasma genitalium during treatment of male urethritis with josamycin

Abstract

BackgroundAzithromycin has been widely used for Mycoplasma genitalium treatment internationally. However, the eradication efficacy has substantially declined recent decade. In Russia, josamycin (another macrolide) is the recommended first-line treatment for M. genitalium infections, however, no data regarding treatment efficacy with josamycin and resistance in M. genitalium infections have been internationally published. We examined the M. genitalium prevalence in males attending an STI clinic in Moscow, Russia from December 2006 to January 2008, investigated treatment efficacy with josamycin in male urethritis, and monitored the M. genitalium DNA eradication dynamics and selection of macrolide resistance in M. genitalium during this treatment.MethodsMicroscopy and real-time PCRs were used to diagnose urethritis and non-viral STIs, respectively, in males (n = 320). M. genitalium positive patients were treated with recommended josamycin regimen and treatment efficacy was monitored using quantitative real-time PCR. Macrolide resistance mutations were identified using sequencing of the 23S rRNA gene.ResultsForty-seven (14.7%) males were positive for M. genitalium only and most (85.1%) of these had symptoms and signs of urethritis. Forty-six (97.9%) males agreed to participate in the treatment efficacy monitoring. All the pre-treatment M. genitalium specimens had wild-type 23S rRNA. The elimination of M. genitalium DNA was substantially faster in patients with lower pre-treatment M. genitalium load, and the total eradication rate was 43/46 (93.5%). Of the six patients with high pre-treatment M. genitalium load, three (50%) remained positive post-treatment and these positive specimens contained macrolide resistance mutations in the 23S rRNA gene, i.e., A2059G (n = 2) and A2062G (n = 1).ConclusionsM. genitalium was a frequent cause of male urethritis in Moscow, Russia. The pre-treatment M. genitalium load might be an effective predictor of eradication efficacy with macrolides (and possibly additional antimicrobials) and selection of macrolide resistance. Additional in vivo and in vitro data are crucial to support the recommendation of using josamycin as first-line treatment for M. genitalium infections in Russia. It would be valuable to develop international M. genitalium management guidelines, and quantitative diagnostic PCRs determining also M. genitalium load and resistance mutations (for macrolides and ideally also moxifloxacin) should ideally be recommended.

Background review for the 2016 European guideline on Mycoplasma genitalium infections

“…Another macrolide, josamycin, is widely used in Russia for treatment of M. genitalium ‐positive patients as first‐line treatment. In a recently published study, josamycin given as 500 mg three times a day for 10 days showed a 93.5% eradication rate in males with urethritis caused by macrolide‐susceptible M. genitalium . Macrolide resistance to this 16‐membered macrolide was reported with approximately the same rate as for azithromycin but the mutation was selected at the A2062G position of the 23S rRNA gene (different from the A2058G/A2059G mutations described for azithromycin).…”

Bacterial Load in Daily Urine Samples of Patients Infected withMycoplasma genitalium, Mutation Analysis, and Response to Treatment

“…Jensen et al found mutations in region V of the 23S rRNA gene in positions 2058 and 2059 ( Escherichia coli numbering) accounting for some of the macrolide failures seen [15]. High bacterial load may also be associated with treatment failure [16, 17]. In cases of treatment failure moxifloxacin, a fluoroquinolone, is recommended as a second line treatment [7].…”

The modern view of the diagnosis and treatment of sexually transmitted mono- and mixed infections

“…Высокую эффективность в лечения МгИ пока-зало использование джозамицина по схеме 500 мг 3 раза в сутки в течение 10 дней, что позволило до-стичь эффективности лечения в 93,5% [46]. Джоза-мицин включен в качестве альтернативного препа-рата для лечения хламидийной инфекции в Реко-мендации IUSTI/ВОЗ и в качестве одного из основ-ных препаратов в рекомендациях РОДВиК 2012 г.…”