Doxycycline and Sitafloxacin Combination Therapy for Treating Highly Resistant Mycoplasma genitalium

Abstract

M ycoplasma 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%

Azithromycin and Doxycycline Resistance Profiles of U.S. Mycoplasma genitalium Strains and Their Association with Treatment Outcomes

“…In this strategy, patients were presumptively treated with DOX while awaiting detection of M. genitalium and MRM SNP typing using the ResistancePlus MG test (SpeeDx, Inc., Sydney, Australia). Patients infected with MRM-containing M. genitalium were treated with sitafloxacin (or moxifloxacin [MXF] in a subsequent study [ 67 ]), while those with the AZM-susceptible allele were treated with high dose azithromycin (2.5 g). This regimen increased microbiologic cure rates to 92.5%, even though prevalence of MRM was 62% in this patient population, and reduced the emergence of AZM resistance during treatment to 2.6% ( 66 , 67 ).…”

“…Patients infected with MRM-containing M. genitalium were treated with sitafloxacin (or moxifloxacin [MXF] in a subsequent study [ 67 ]), while those with the AZM-susceptible allele were treated with high dose azithromycin (2.5 g). This regimen increased microbiologic cure rates to 92.5%, even though prevalence of MRM was 62% in this patient population, and reduced the emergence of AZM resistance during treatment to 2.6% ( 66 , 67 ). Accordingly, the UK ( 42 ) and Australian ( http://www.sti.guidelines.org.au/sexually-transmissible-infections/mycoplasma-genitalium ) guidelines recommend resistance-guided treatment strategies.…”

Emergence and Mechanism of Resistance of Tulathromycin Against Mycoplasma hyopneumoniae in a PK/PD Model and the Fitness Costs of 23S rRNA Mutants

“…Doxycycline combined with sitafloxacin also had a good therapeutic effect on multidrugresistant M. genitalium. At the same time, under this combined treatment there was only one parC G248T / S83I mutation and no gyrA mutations (56). Therefore, rotation and combination of medications provide a way to prevent drug resistance.…”

Initial Failure of Pristinamycin Treatment in a Case of Multidrug-Resistant Mycoplasma genitalium Urethritis Eventually Treated by Sequential Therapy

“…11 Durukan et al reported 11/12 cured MG infections using doxycycline and sitafloxacine combination therapy, after pristinamycin failure. 12 However, sitafloxacine is not available in France.…”