Evaluation of Ceftaroline (CPT) Activity versus Ceftriaxone (CRO) Against Clinical Isolates of Streptococcus pneumoniae with Varying Susceptibilities to Cephalosporins in an in-vitro Pharmacokinetic/Pharmacodynamic (PK/PD) Model.
Antimicrob Agents Chemother. 2012 Feb 21;
Authors: Steed ME, Vidaillac C, Winterfield P, Biek D, Rybak MJ
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 600 mg q 12 h (fCmax=15.2 ?g/mL, T(1/2)=2.5 h) vs. ceftriaxone 1 g q 24 h (fCmax=23 ?g/mL, T(1/2)=8 h) against six clinical S. pneumoniae isolates in an one-compartment in vitro PK/PD 96 h model (starting inoculum of 10(7) CFU/mL). Differences in CFU/mL (at 24-96 h) were evaluated by ANOVA 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 ?g/mL and ceftriaxone MICs were 0.5, 0.25, 0.25, 4, 4, and 8 ?g/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 - 96 h, - 6.48 log(10) CFU/mL) and was significantly (p ? 0.012) better than ceftriaxone (72-96 h, -2.03 log(10) CFU/mL). Against the ceftriaxone resistant strains, ceftaroline displayed sustained bactericidal activity at 96 h and was significantly better than ceftriaxone [SP211 (-5.91 log(10) CFU/mL, p ? 0.002), SP 90 (-5.26 log(10) CFU/mL, p ? 0.008), and SP1466 (-5.14 log(10) CFU/mL, p ? 0.042).] Ceftaroline was the most effective drug and displayed sustained bactericidal activity. Ceftaroline fosamil may provide a therapeutic option to treat ceftriaxone resistant S. pneumoniae infections.
PMID: 22354289 [PubMed - as supplied by publisher]