How should I manage a patient with Mycoplasma genitalium who is resistant to first-line antibiotics?

Management of Mycoplasma genitalium infection resistant to first-line antibiotics requires a resistance-guided treatment approach to optimise outcomes and reduce further resistance development. Initially, confirm resistance to first-line agents such as azithromycin or doxycycline through molecular testing for macrolide and fluoroquinolone resistance mutations ¹.

If macrolide resistance is detected, the recommended next step is to use alternative antibiotics guided by resistance profiles, typically involving moxifloxacin as a second-line agent due to its efficacy against resistant strains ¹. However, emerging resistance to fluoroquinolones necessitates consideration of newer or combination therapies.

Recent literature supports expanded resistance-guided strategies, including the use of pristinamycin or combination regimens (e.g., doxycycline followed by sitafloxacin or moxifloxacin) in cases where both macrolide and fluoroquinolone resistance are present (Sweeney et al., 2022). Additionally, Qiu et al. (2024) highlight advances in genitourinary infection management that suggest tailoring therapy based on local resistance patterns and incorporating novel agents or extended treatment durations to overcome resistance.

Close follow-up with test-of-cure at least 3 weeks post-treatment is essential to confirm eradication and guide further management ¹. In summary, managing resistant Mycoplasma genitalium involves resistance testing, use of second-line agents like moxifloxacin, and consideration of alternative or combination therapies informed by emerging evidence, with careful monitoring to prevent treatment failure and resistance spread.