Doxycycline and Sitafloxacin Combination Therapy for Treating Highly Resistant Mycoplasma genitalium

Duygu Durukan; Michelle Doyle; Gerald Murray; Kaveesha Bodiyabadu; Lenka Vodstrcil; Eric P.F. Chow; Jorgen S. Jensen; Christopher K. Fairley; Ivette Aguirre; Catriona S. Bradshaw

Disclosures

Emerging Infectious Diseases. 2020;26(8):1870-1874. 

In This Article

Abstract and Introduction

Abstract

Antimicrobial-resistant Mycoplasma genitalium is becoming increasingly common and creating major treatment challenges. We present early data on combination therapy with doxycycline and sitafloxacin to treat highly resistant M. genitalium. We found the regimen was well tolerated and cured 11/12 infections that had failed prior regimens with moxifloxacin and pristinamycin.

Introduction

Mycoplasma genitalium is a sexually transmitted bacterium with marked capacity for developing antimicrobial resistance.[1] Macrolides and 4th-generation fluroquinolones, such as moxifloxacin, have been the main agents displaying efficacy against M. genitalium. However, macrolide resistance has increased to >50% in many nations, and quinolone resistance is increasing.[2–6] In Australia, 16% of M. genitalium strains are reported to have dual-class resistance,[5] and Japan reports dual-class resistance of up to 25%,[2] resulting in infections that often cannot be cured with current recommended therapies.

Sequential monotherapy with doxycycline followed by moxifloxacin[7–9] is currently first-line therapy for macrolide-resistant M. genitalium in guidelines in Australia and the United Kingdom and achieves cure in 92% of cases (95% CI 88.1%–94.6%) at our service.[7] When the doxycycline/moxifloxacin sequential regimen fails, we use a pristinamycin-based regimen, which achieves 75% cure (95% CI 66%–82%).[10] Since August 2017, for patients in whom both regimens failed, we administered a combination of 100 mg doxycycline and 100 mg sitafloxacin 2 times/day for 7 days.

Access to sitafloxacin is limited in many countries, but it is available in the Asia-Pacific region. Most publications on sitafloxacin are from Japan, where its use as a monotherapy is reported to cure ≈90% of M. genitalium infections.[11] However, combination therapies can optimize cure and prevent further resistance in bacteria prone to developing resistance, such as M. genitalium. In vitro, a combination of doxycycline and sitafloxacin (doxycycline+sitafloxacin) shows synergy for quinolone-susceptible M. genitalium strains but has not been evaluated for highly resistant strains (J.S. Jensen, unpub. data). We provide early data on the efficacy and tolerability of a 7-day doxycycline+sitafloxacin combination therapy for treatment-resistant M. genitalium. The ethics committee of Alfred Hospital (Melbourne) approved this study (approval no. 232/16).

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