Laboratory and clinical studies on meropenem

A newly developed broad-spectrum carbapenem, meropenem (MEPM), was evaluated in vitro and in vivo in comparison with imipenem (IPM), ceftazidime, ceftizoxime, cefuzonam and piperacillin. The results were as follows; 1. Antimicrobial activity: Minimal inhibitory concentrations (MICs) against 480 clinical isolates including 15 different species were determined by the microbroth dilution method. MEPM showed excellent antimicrobial activity against gram-positive and-negative bacteria. The MIC values of MEPM for gram-positive bacteria were slightly inferior to those of IPM, but superior to those of the other antibiotics tested. Against gram-negative bacteria, including Pseudomonas aeruginosa, MEPM showed the best antibacterial activity among the antibiotics tested. 2. MEPM concentrations in serum and sputum: MEPM was intravenously administered in a single dose of 500 mg to two patients, one with bronchiectasis and the other with diffuse panbronchiolitis (DPB) complicated with chronic renal failure, and its concentrations in serum and sputum were measured at various intervals by bioassay. The peak concentrations of MEPM in serum were observed immediately after intravenous injection: 32 µg/ml in the bronchiectasis patient and 27 µg/ml in the DPB patient. The peak concentrations in sputum were 0.37 µg/ml at 4 hours after administration in the former patient, and 3.6 µg/ml after 7 hours in the latter patient. 3. Clinical efficacy and adverse reactions: Nineteen patients with respiratory tract infections were treated with MEPM, and the overall efficacy rate was 81.3% (excellent in 5 cases, good in 8, fair in 3, unjudged in 3). No side effects were observed. Although leukocytopenia in one case, eosinophilia in two cases and elevation of GOT, GPT and/or ALP in 4 cases were observed as abnormal laboratory findings, they were mild and transient, and improved rapidly after the completion of MEPM treatment.