Differences in therapeutic efficacy among cell wall-active antibiotics in a mouse model of gram-negative sepsis.
The in vivo efficacy of three cell wall-active antibiotics, imipenem, meropenem, and ceftazidime, was compared in mice rendered hypersusceptible to the pathophysiologic effects of lipopolysaccharide by treatment with D-galactosamine. When CF-1 mice were administered Escherichia coli, D-galactosamine, and saline intraperitoneally, an LD50 was achieved at an inoculum of approximately 2 x 10(4) cfu. Administration of antibiotic at 20 mg/kg resulted in significant but widely variable protective efficacy from E. coli lethality among the three antibiotics. At this dose, an approximately 3-fold increase in LD50 was observed with either meropenem or ceftazidime, whereas administration of imipenem resulted in an approximately 8-fold increase in LD50 (P = .0053). When the dose of antibiotic was decreased to 2 mg/kg, neither meropenem nor ceftazidime could provide measurable protection, whereas imipenem was almost fully protective (P < .002). These differences in protective efficacy were also noted with experimental Pseudomonas aeruginosa but not Staphylococcus aureus infection.
Bucklin
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Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City 66160, USA.
Morrison
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DC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002442:Ceftazidime / Q000627:therapeutic use; D002473:Cell Wall / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D005260:Female; D005688:Galactosamine / Q000494:pharmacology; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D015378:Imipenem / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D018805:Sepsis / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D015378:Imipenem; D005688:Galactosamine; D002442:Ceftazidime