Understanding the spread of de novo and transmitted macrolide-resistance in Mycoplasma genitalium

Dominique Cadosch; Victor Garcia; Jørgen S Jensen; Nicola Low; Christian L Althaus

doi:10.7717/peerj.8913

Understanding the spread of de novo and transmitted macrolide-resistance in Mycoplasma genitalium

PeerJ. 2020 Apr 7:8:e8913. doi: 10.7717/peerj.8913. eCollection 2020.

Authors

Dominique Cadosch¹, Victor Garcia^{1

2}, Jørgen S Jensen³, Nicola Low¹, Christian L Althaus¹

Affiliations

¹ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
² School of Life Sciences and Facility Management, Zurich University of Applied Sciences, Wädenswil, Switzerland.
³ Research Unit for Reproductive Tract Microbiology, Statens Serum Institut, Copenhagen, Denmark.

Abstract

Background: The rapid spread of azithromycin resistance in sexually transmitted Mycoplasma genitalium infections is a growing concern. It is not yet clear to what degree macrolide resistance in M. genitalium results from the emergence of de novo mutations or the transmission of resistant strains.

Methods: We developed a compartmental transmission model to investigate the contribution of de novo macrolide resistance mutations to the spread of antimicrobial-resistant M. genitalium. We fitted the model to resistance data from France, Denmark and Sweden, estimated the time point of azithromycin introduction and the rates at which infected individuals receive treatment, and projected the future spread of resistance.

Results: The high probability of de novo resistance in M. genitalium accelerates the early spread of antimicrobial resistance. The relative contribution of de novo resistance subsequently decreases, and the spread of resistant infections in France, Denmark and Sweden is now mainly driven by transmitted resistance. If treatment with single-dose azithromycin continues at current rates, macrolide-resistant M. genitalium infections will reach 25% (95% confidence interval, CI [9-30]%) in France, 84% (95% CI [36-98]%) in Denmark and 62% (95% CI [48-76]%) in Sweden by 2025.

Conclusions: Blind treatment of urethritis with single-dose azithromycin continues to select for the spread of macrolide resistant M. genitalium. Clinical management strategies for M. genitalium should limit the unnecessary use of macrolides.

Keywords: Antibiotic resistance; Mathematical model; Mycoplasma genitalium; Sexually transmitted infection.

Grants and funding

This work was supported by the Swiss National Science Foundation through the Epidemiology and Mathematical Modelling in Infectious Diseases Control (EpideMMIC) project (grant number 32003B 160320). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.