In vitro activity of ceftobiprole against key pathogens associated with pneumonia in hospitalized patients: results from the PEG surveillance study, 2010

Abstract

Empirical treatment of hospital-acquired pneumonia (HAP) has increasingly been threatened by methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistant Gram-negative pathogens. In contrast, empirical treatment of community-acquired pneumonia (CAP) is primarily impeded by antimicrobial-resistant pneumococci. Ceftobiprole, recently approved for the treatment of HAP and CAP in Europe, is active against a broad-spectrum of Gram-positive and Gram-negative pathogens, including MRSA and Pseudomonas aeruginosa. The objective of this study was to evaluate the susceptibility of ceftobiprole among 1,246 S. aureus, Streptococcus pneumoniae, Enterobacteriaceae species and P. aeruginosa isolated from respiratory tract and blood. Isolates were collected in 25 laboratories across Germany, Switzerland and Austria. Minimum inhibitory concentrations (MICs) were determined using the microdilution method according to the standard ISO 20776-1:2006 and interpreted by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. Two-thirds of the isolates were obtained from respiratory specimens and one third from blood. There were 544 intensive care unit (ICU) isolates and 702 non-ICU isolates. The share of MRSA in S. aureus was 16%. Among pneumococci, 18.5% showed reduced susceptibility to penicillin. An extended-spectrum β-lactamase (ESBL) phenotype was confirmed for 18.4% of the Escherichia coli and 16.7% of the Klebsiella pneumoniae isolates. Of the P. aeruginosa isolates, 20.7% were ceftazidime-resistant. MIC50/90 values of ceftobiprole for methicillin-susceptible S. aureus (MSSA) and MRSA were 0.5/0.5 mg/L and 2/2 mg/L, respectively. All pneumococci were inhibited at 1 mg/L ceftobiprole. The activity of ceftobiprole against E. coli and K. pneumoniae was similar to that of ceftriaxone, but ceftobiprole showed superior activity against Enterobacteriaceae species known to produce chromosomally encoded AmpC-β-lactamases. MIC50/90 values of ceftobiprole for ceftazidime-susceptible (4/16 mg/L) and ceftazidime-resistant P. aeruginosa (16/>32 mg/L) were comparable to those of cefepime (4/8 mg/L and 32/>32 mg/L, respectively). These findings suggest that ceftobiprole may represent a suitable option for the empirical treatment of HAP and CAP.