In vitro activity of ceftaroline (PPI-0903M, T-91825) against bacteria with defined resistance mechanisms and phenotypes

作者：Shazad Mushtaq, Marina Warner, Yigong Ge, Koné Kaniga, David M. Livermore · 发表于：Journal of Antimicrobial Chemotherapy · 年份：2007 · DOI：10.1093/jac/dkm150 · 被引用次数：133 · 研究领域：Antimicrobial Resistance in Staphylococcus、Antibiotic Resistance in Bacteria、Bacterial biofilms and quorum sensing

BACKGROUND: Ceftaroline (PPI-0903M, T-91825) is a novel cephalosporin, administered as an N-phosphono prodrug. We investigated its in vitro activity and resistance selection potential. METHODS: MICs were determined by CLSI agar dilution, but with varied inocula. Mutant selection was investigated in single- and multi-step procedures. RESULTS: MICs for methicillin-resistant Staphylococcus aureus (MRSA) were 0.5-2 mg/L, compared with 0.12-0.25 mg/L for methicillin-susceptible S. aureus; corresponding values for coagulase-negative staphylococci were 0.25-2 and 0.06-0.12 mg/L, respectively. Even with 2% NaCl added, all MRSA were susceptible at 2 mg/L. MICs for Enterococcus faecalis were from 0.25 to 8 mg/L; E. faecium was resistant. MICs for Escherichia coli, Klebsiella spp., Morganella morganii and Proteeae without acquired resistance were 0.06-0.5 mg/L versus 0.12-1 mg/L for Enterobacter, Serratia and Citrobacter spp. and 2-8 mg/L for Acinetobacter spp. MICs rose to 1-2 mg/L for many Enterobacteriaceae with classical TEM beta-lactamases, and were much higher for those with extended-spectrum beta-lactamases (ESBLs), hyperproduced AmpC or K1 enzymes. MICs for strains with classical TEM/SHV beta-lactamases rose if the inoculum was increased to 10(6) cfu/spot; this effect was even more marked for those with ESBLs. Resistance due to Class A beta-lactamases was reversed by clavulanate. Geometric mean MICs were 0.005, 0.05 and 0.09 mg/L for penicillin-susceptible, -intermediate and -re...