Prolonged sitafloxacin and doxycycline combination regimen for treating infections by highly resistant Mycoplasma genitalium

Mycoplasma genitalium, which causes sexually transmitted diseases, is increasingly resistant to key antibiotics such as macrolides and quinolones, posing a challenge for treatment. To assess the effectiveness of prolonged sitafloxacin and doxycycline combination therapy as a new alternative treatment strategy for highly drug-resistant M. genitalium strains. A prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan, from 1 January 2020 to 31 October 2022. Patients with M. genitalium urogenital or rectal infections and those who did not receive the initial sitafloxacin monotherapy were included. Patients were administered sitafloxacin and doxycycline for 21 days as salvage therapy. M. genitalium isolates were tested for parC, gyrA and 23S rRNA resistance-associated mutations. Twenty-seven patients received the combination therapy. All M. genitalium strains available for resistance analysis had parC (24/24) and macrolide resistance-associated (25/25) mutations, and 68% (17/25) had gyrA mutations. The overall cure rate was 77.8%. For strains with concurrent parC and gyrA mutations, the cure rate was 68.8% (P = 0.053) compared with that for monotherapy (37.5%). Prolonged combination therapy is highly effective against M. genitalium strains with concurrent parC and gyrA mutations. Future research should focus on establishing the optimal treatment duration and monitoring the risk of resistance.