In vitro and in vivo antibacterial activities of meropenem, a new carbapenem antibiotic.
The in vitro and in vivo antibacterial activities of meropenem were compared with those of imipenem, ceftazidime, flomoxef, cefuzonam and cefotiam. Meropenem showed a broad antibacterial spectrum against clinical isolates of Gram-positive and Gram-negative bacteria. Against Gram-negative bacteria, with the exception of Acinetobacter calcoaceticus, meropenem exhibited the most potent activity among the drugs tested. It inhibited all 330 strains of Enterobacteriaceae at 0.78 mg/l. Meropenem was sensitive against several cephem-resistant strains of Enterobacteriaceae. Against Pseudomonas aeruginosa, meropenem was four-fold more active than imipenem and eight-fold more active than ceftazidime, with an MIC90 of 0.78 mg/l. The therapeutic effect of meropenem on systemic infection in mice was ten to twenty-fold less than that of imipenem against Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae. However, meropenem was as effective as imipenem on infections of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Acinetobacter calcoaceticus and Pseudomonas aeruginosa. Meropenem was eliminated from mice plasma two-fold faster than imipenem, with a plasma half-life of 7.6 min. From the above results the authors concluded that meropenem is a promising drug for clinical use.
Harabe
E
E
Department of Microbiology, Kyoto Pharmaceutical University, Japan.
Kawai
Y
Y
Kanazawa
K
K
Otsuki
M
M
Nishino
T
T
D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D002511:Cephalosporins / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D015378:Imipenem / Q000494:pharmacology; D008297:Male; D000077731:Meropenem; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D013845:Thienamycins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D002511:Cephalosporins; D013845:Thienamycins; D015378:Imipenem; D000077731:Meropenem