Treatment variability among people assigned male at birth with repeat positive Mycoplasma genitalium tests: a case series

BACKGROUND: Mycoplasma genitalium (MG) can cause nongonococcal urethritis (NGU) and symptomatic proctitis. Rising antimicrobial resistance and lack of clinically available molecular resistance assays make MG treatment challenging. This study adds systematic data on the effectiveness of alternative MG regimens. METHODS: Adult natal male patients who attended a public Sexual Health Clinic (SHC) and had ≥2 positive MG nucleic acid amplification tests within any 6-month period from January 2023-September 2025 were included. We classified cases as persistent infection or reinfection using clinical, demographic and self-reported behavioral data. For each patient, we summarized total number of visits, number, duration and components of each antibiotic regimen, and outcomes by MG clinical syndrome and infection status (persistence vs reinfection). RESULTS: Among 3,009 SHC patients, 400 (13%) had incident MG and 19 (4.8%) met inclusion criteria for repeat MG infection across 61 clinic visits. Nongonococcal urethritis (n=14/19 patients, 74%) and proctitis (n=2/19 patients, 10%) were the most prevalent syndromes. Suspected reinfection was common (40%). All 19 patients achieved cure, including 10 (53%) with microbiologic and 9 (47%) with presumed clinical cure, after treatment for a mean of 18-49 days with between 1-9 antibiotic regimens. Eight (53%) patients were cured with doxycycline plus moxifloxacin, two (100%) with doxycycline plus pristinamycin, three (75%) with minocycline alone, and three (75%) with prolonged minocycline plus tinidazole treatment. CONCLUSIONS: Despite frequent reinfection, most repeat positive tests represented persistent MG infections. All cases achieved cure after initial treatment failure, but many required multiple regimens over several weeks.