Combination therapy for multidrug-resistant Mycoplasma genitalium infections: a case series

Objectives In Belgium, approximately a quarter of Mycoplasma genitalium infections are resistant to both macrolides and fluoroquinolones—termed multidrug-resistant (MDR) infections. The optimal treatment approach for these MDR infections remains uncertain. Combination therapy has shown promise in treating other MDR pathogens by enhancing efficacy and reducing resistance development. We report the first five cases of MDR M. genitalium urethritis successfully treated with a novel combination therapy regimen consisting of minocycline, metronidazole, methenamine and pristinamycin (‘M3P’).

Methods We describe a case series of five individuals treated with M3P as salvage therapy for M. genitalium urethritis. Clinical data, laboratory findings, resistance profiles and treatment outcomes were reviewed.

Results All five men with macrolide-resistant and fluoroquinolone-resistant M. genitalium urethritis received M3P for a minimum of 14 days. Two men received an extended 28-day M3P regimen, in which minocycline and methenamine were given for 28 days. All five patients experienced clinical and microbiological cure. Adverse effects were minimal and transient, with one patient reporting increased urinary frequency during treatment and another reporting mild dyspepsia.

Conclusions This case series demonstrates the potential efficacy of M3P as a novel salvage therapy for MDR M. genitalium urethritis, particularly where standard therapies have failed. The combination of pristinamycin, methenamine, and other agents may synergistically reduce bacterial load and increase efficacy. Further, in vitro and clinical studies are required to assess the optimal treatment strategies for MDR M. genitalium.