Meropenem / Clavulanate

Beta-lactam antibiotics are ineffective against Mycobacterium tuberculosis, being rapidly hydrolyzed by the chromosomally encoded blaC beta-lactamase. The carbapenem class of b-lactams are very poor substrates for BlaC. Meropenem and clavulanate are US FDA–approved drugs and could potentially be used to treat patients with currently untreatable disease. A clinical trial was developed to evaluate the early bactericidal activity (EBA), safety, tolerability and pharmacokinetics of meropenem administered intravenously three times a day, plus amoxycillin/CA administered orally three times a day; and of faropenem administered orally three times a day, plus amoxycillin/CA administered orally three times a day. Drugs were administered for 14 consecutive days, in adult participants with newly diagnosed, smear positive pulmonary tuberculosis, in order to help establish proof-of-concept for carbapenem antibiotics as antituberculosis agents and to select the appropriate agent and route of administration for later stage clinical development.