Mecillinam against genital Chlamydia trachomatis infection: a small-scale proof-of-concept study shows a low cure rate

Mecillinam is highly active in vitro against Chlamydia spp. We aimed to determine whether mecillinam should be evaluated further as treatment for genital Chlamydia trachomatis infection. The study was conducted at an open-access clinic for sexually transmitted infections in Oslo, Norway. We planned to include 50 patients. Participants were asymptomatic, heterosexual male patients with a first-void urine sample found to be positive for C. trachomatis by PCR. Treatment consisted of 400 mg of pivmecillinam hydrochloride three times a day for 7 days. A test-of-cure sample, a medication diary and a questionnaire were returned by the participants, and they were used to evaluate treatment outcome, compliance, risk of reinfection and theoretical percentage of time above MIC (t/MIC %). The study was registered in Eudra-CT (no. 2013-002379-179) and clinicaltrals.gov (NCT02083276). The study was discontinued after including 20 patients, due to a high failure rate. Only two of the 17 participants who delivered a test-of-cure sample were cured. Three participants reported condomless sex before the follow-up sample. When the average or most favourable pharmacokinetics (PK)/pharmacodynamics (PD) reported from other studies were applied in a theoretical model, the estimated t/MIC % was above 50% for all of the 15 participants returning a medication diary. Using the least favourable PK/PD, no participant had t/MIC % of >36%. The mean dose interval was 8 h 36 min (standard deviation 3 h 12 min). A low cure rate combined with uncertainty about intracellular availability and attained t/MIC % makes mecillinam an unattractive candidate for further evaluation as treatment for genital C. trachomatis infection.