Evaluation of ceftaroline activity versus ceftriaxone against clinical isolates of Streptococcus pneumoniae with various susceptibilities to cephalosporins in an in vitro pharmacokinetic/pharmacodynamic model.

Antimicrobial Agents and Chemotherapy
Molly E SteedMichael J Rybak

Abstract

Drug resistance in Streptococcus pneumoniae, a frequent pathogen in community-acquired pneumonia, is increasing. Ceftaroline (active metabolite of ceftaroline fosamil) is a broad-spectrum intravenous cephalosporin with activity in vitro against drug-resistant Gram-positive organisms. We investigated ceftaroline at 600 mg every 12 h (q12h) (maximum concentration of the free, unbound drug in serum [fC(max)] is 15.2 μg/ml, and half-life [T(1/2)] is 2.5 h) versus ceftriaxone at 1 g q24h (fC(max) = 23 μg/ml, T(1/2) = 8 h) against six clinical S. pneumoniae isolates in a one-compartment in vitro pharmacokinetic/pharmacodynamic 96-h model (starting inoculum of 10(7) CFU/ml). Differences in CFU/ml (at 24 to 96 h) were evaluated by analysis of variance with a Tukey's post hoc test. Bactericidal activity was defined as a ≥ 3 log(10) CFU/ml decrease from the initial inoculum. Ceftaroline MICs were 0.06, 0.015, ≤ 0.008, 0.25, 0.25, and 0.5 μg/ml, and ceftriaxone MICs were 0.5, 0.25, 0.25, 4, 4, and 8 μg/ml for SP 1477, SP 669, SP 132, SP 211, SP 90, and SP 1466, respectively. Against the ceftaroline- and ceftriaxone-susceptible strain SP 1477, ceftaroline displayed sustained bactericidal activity (3 to 96 h, -5.49 log(10) CFU/ml) and was s...Continue Reading

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