Comparative ceftaroline activity tested against pathogens associated with community-acquired pneumonia: results from an international surveillance study

Objectives: To document the spectrum of activity of ceftaroline, the active form of the prodrug, ceftaroline fosamil, a new cephalosporin with anti-methicillin-resistant staphylococcal activity, against a surveillance collection of clinical isolates obtained from the USA and Europe during 2008-09. Methods: A selected group of species associated with community-acquired pneumonia (CAP; 6496 of 17326 monitored strains) were tested for susceptibility in a central laboratory using CLSI broth microdilution methods. Organisms were sampled from 55 medical centres, 27 in the USA and 28 (12 countries) in Europe. Ceftaroline and comparator agents were tested and interpretations of MIC endpoints made by applying current CLSI (2010) and EUCAST (2010) breakpoint criteria. Results: Against 1340 Streptococcus pneumoniae, ceftaroline inhibited all isolates at <= 0.5 mg/L (MIC50/90, <= 0.008/0.12 mg/L) and was 8-fold more active than ceftriaxone (MIC90, 1 mg/L; only 79.2% coverage at EUCAST breakpoint). Haemophilus influenzae (n=584; MIC50/90, <= 0.008/0.015 mg/L), Moraxella catarrhalis (n=377; MIC50/90, 0.03-0.06/0.12 mg/L) and Staphylococcus aureus (n=590; MIC50/90, 0.5/1 mg/L) were very susceptible to ceftaroline, regardless of beta-lactamase production or multidrug resistance (MDR) patterns. The potency of ceftaroline against three species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae) was similar to that of ceftriaxone, ceftazidime and piperacillin/tazobactam. Only modest differences in rates of ceftaroline susceptibility (breakpoint <= 2 mg/L) were noted with extended-spectrum beta-lactamase-negative Enterobacteriaceae strains between the USA and Europe (97.9% versus 97.0% for E. coli). Ceftaroline, like ceftriaxone, was not active against ceftazidime-resistant E. coli (10.2%-26.2% susceptible at <= 2 mg/L) or K. pneumoniae (5.3%-11.2%). Conclusions: The ceftaroline surveillance for 2008-09 (USA and Europe) documented low MIC50/90 values for S. aureus isolates at 0.5/1 and 0.25/1 mg/L, respectively. More importantly, ceftaroline MIC90 results for S. pneumoniae (0.12 mg/L), H. influenzae (0.015 mg/L) and M. catarrhalis (0.12 mg/L) were very low, all MICs being <= 0.5 mg/L. Ceftaroline exhibited promising high potency and wide coverage against Gram-positive and -negative pathogens known to cause CAP, especially isolates of MDR pneumococci and methicillin-resistant S. aureus.