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

J Antimicrob Chemother. 2016 Aug;71(8):2270-2. doi: 10.1093/jac/dkw134. Epub 2016 May 10.

Abstract

Objectives: 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.

Patients and methods: 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).

Results: 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).

Conclusions: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amdinocillin / administration & dosage*
  • Anti-Infective Agents, Urinary / administration & dosage*
  • Chlamydia trachomatis / drug effects*
  • Humans
  • Lymphogranuloma Venereum / drug therapy*
  • Male
  • Middle Aged
  • Norway
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Infective Agents, Urinary
  • Amdinocillin

Associated data

  • ClinicalTrials.gov/NCT02083276