Efficacy of human simulated exposures of ceftaroline against phenotypically diverse Enterobacteriaceae isolates.

Antimicrobial Agents and Chemotherapy
Seth T HousmanDavid P Nicolau

Abstract

Ceftaroline fosamil, a new broad-spectrum cephalosporin, exhibits potent bactericidal activity against common Gram-negative pathogens, including Enterobacteriaceae, and Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. The purpose of this study was to evaluate the efficacy of a human simulated dose of ceftaroline fosamil against clinical Enterobacteriaceae in both neutropenic and immunocompetent mouse thigh infection models. Thirty-five Enterobacteriaceae isolates with ceftaroline MICs ranging from 0.25 to 32 μg/ml were selected for the neutropenic model, and five Escherichia coli isolates were also tested in the immunocompetent model. Two hours after inoculation, the ceftaroline fosamil human simulated regimen of 600 mg intravenously (i.v.) every 12 h was administered. The change in log(10) CFU after 24 h was compared to that in 0 h controls. The human simulated regimen produced predictable efficacy against 18 of 20 isolates with a MIC of ≤ 1 μg/ml. Similar efficacy was seen in the immunocompetent model against isolates with a MIC of ≤ 2 μg/ml, and enhanced efficacy was observed against the isolate with a MIC of 4 μg/ml. Human simulated exposures t...Continue Reading

References

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Citations

Sep 4, 2014·Arquivos Brasileiros De Cirurgia Digestiva : ABCD = Brazilian Archives of Digestive Surgery·Paula Virginia Michelon ToledoAyrton Alves Aranha-Junior
Feb 6, 2014·Expert Review of Clinical Pharmacology·Eric BeresfordH David Friedland
Mar 30, 2017·Journal of Pharmacokinetics and Pharmacodynamics·Catharine C BulikPaul G Ambrose

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