Macrolide resistance in Mycoplasma genitalium from female sex workers in Belgium

Highlights

• First report on macrolide resistance-associated mutations in M. genitalium in FSW in Belgium.

• Second report on the occurrence of macrolide resistance in this specific population worldwide.

• M. genitalium was detected in 32/296 (10.8%) of participants.

• Macrolide-resistance associated mutations (A2058G and A2059G) were found in 6.5% of isolates.

• In contrast to other reports, the occurrence of macrolide resistance appears limited in this specific population.

Abstract

Objectives

Mycoplasma genitalium is emerging as an aetiological agent of sexually transmitted infections (STIs). Although M. genitalium is commonly treated with azithromycin, macrolide resistance associated with point mutations in the 23S rRNA gene is emerging.

Methods

In this study, the prevalence of M. genitalium and macrolide resistance in female sex workers (FSW) in Belgium was evaluated by a prospective study conducted between 2015 and 2016. Vaginal swabs were sampled from 303 FSW who underwent testing for M. genitalium along with standard STI screening. All samples positive for M. genitalium were subsequently tested for mutations associated with macrolide resistance.

Results

M. genitalium was detected in 10.8% of participants and macrolide resistance-associated mutations (A2058G and A2059G) were found in 6.5% of isolates.

Conclusions

M. genitalium is clearly present in FSW in Belgium. In contrast to other reports, for now the occurrence of macrolide resistance appears limited in this specific target population.

Introduction

Mycoplasma genitalium is an emerging sexually transmitted infection (STI). The bacterium has been identified as the causative organism of non-gonococcal urethritis (NGU), cervicitis, endometritis, pelvic inflammatory disease, infertility, preterm delivery and increased transmission of human immunodeficiency virus (HIV) [1]. Prevalence estimates for M. genitalium vary greatly worldwide, with community-based studies estimating a maximum prevalence of 3.3% in women and 1.1% in men [2].

As M. genitalium lacks a rigid peptidoglycan-containing cell wall, antibiotics targeting the cell wall (e.g. β-lactam antibiotics) are inactive against this bacterium; however, in vitro studies showed high susceptibility to tetracyclines, macrolides and moxifloxacin [3], [4]. The majority of M. genitalium infections and associated syndromes are presumptively treated with 1 g of azithromycin, which is recommended due to superior cell penetration and ease of single-dose administration [5]. However, a recent meta-analysis found that the efficacy of this treatment regimen has decreased over the last 5 years and is now approaching 60%, which is well below the 95% threshold recommended by the World Health Organization (WHO) for the treatment of STIs [2]. The underlying mechanism in the development of macrolide resistance is single base mutations in nucleotide 2058 or 2059 (Escherichia coli numbering) in region V of the 23S rRNA gene. These mutations can be present before initiation of treatment, but resistance is attributed mainly to prior treatment with a 1 g single dose of azithromycin [6], [7]. In view of this phenomenon, recent European guidelines no longer recommend the 1 g dose as first-line therapy for NGU in men [5]. As slow-growing bacteria such as M. genitalium require treatment for an extended period of 5 days, the preferred treatment regimen consists of the ‘1.5 g schedule’: 500 mg once on the first day, followed by 250 mg once daily from Days 2–5 [8]. Whether or not to screen for M. genitalium and macrolide resistance and how to treat in case of infection has become an important point of discussion.

In Belgium, testing for M. genitalium is not reimbursed and therefore is not widely adopted. Moreover, there are no commercial assays available to test for macrolide resistance. This study explored the presence of M. genitalium and mutations associated with macrolide resistance in a population of female sex workers (FSW) in Belgium.