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, Dgalactosamine,...

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Bibliographic Details
Published in:The Journal of infectious diseases 1995-12, Vol.172 (6), p.1519-1527
Main Authors: Bucklin, Scott E., Morrison, David C.
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - therapeutic use
Antibacterial agents
Antibiotics
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antibodies, Monoclonal - therapeutic use
Bacteria
Biological and medical sciences
Ceftazidime - therapeutic use
Cell Wall - drug effects
Cell walls
Dosage
Endotoxins
Escherichia coli
Escherichia coli Infections - drug therapy
Female
Galactosamine - pharmacology
Gram-Negative Bacterial Infections - drug therapy
Imipenem - therapeutic use
Infections
Lethal dose 50
Lipopolysaccharides - toxicity
Major Articles
Medical sciences
Mice
Mice, Inbred C3H
Pharmacology. Drug treatments
Pseudomonas aeruginosa
Sepsis
Sepsis - drug therapy
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Summary: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, Dgalactosamine, and saline intraperitoneally, an LD50 was achieved at an inoculum of ∼2 × 104 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 ∼3-fold increase in LD50 was observed with either meropenem or ceftazidime, whereas administration of imipenem resulted in an ∼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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/172.6.1519