Ceftaroline activity against pathogens associated with complicated skin and skin structure infections: results from an international surveillance study

Abstract

To assess the spectrum and potency of ceftaroline, a novel anti-methicillin-resistant staphylococcal cephalosporin, against a 2008 surveillance collection of clinical isolates from patients in the USA and Europe. A collection of 14 169 isolates of various bacterial species from complicated skin and skin structure infections (cSSSIs) was tested for susceptibility to ceftaroline and 19 comparator agents in a central reference laboratory using CLSI broth microdilution methods. Organisms were received from 55 medical centres; 27 in the USA and 28 in Europe (12 countries, including Israel). The clonality of isolates of Staphylococcus aureus with elevated ceftaroline MICs (4 mg/L) was determined by PFGE and single and multilocus sequence typing, and the mechanism of ceftaroline non-susceptibility was assessed by molecular methods (PCR amplification and sequencing). Ceftaroline, the active component of the parenteral prodrug ceftaroline fosamil, was active against 2988 methicillin-resistant S. aureus (MRSA) isolates, with an MI₉₀ of 1 mg/L. The MIC₉₀ for methicillin-susceptible strains was 0.25-0.5 mg/L. Ceftaroline was additionally active against coagulase-negative staphylococci (MIC₉₀, 0.5-1 mg/L), Enterococcus faecalis (MIC₅₀, 2 mg/L), β-haemolytic and viridans group streptococci (MIC₉₀, 0.015-0.25 mg/L) and three commonly isolated Enterobacteriaceae (Escherichia coli, Klebsiella spp. and Proteus mirabilis; MIC₉₀ values of 0.25 to > 16 mg/L). All but four isolates of MRSA (0.13%) had ceftaroline MIC values of ≤ 2 mg/L. The isolates for which ceftaroline MICs were 4 mg/L were clonal (single Greek hospital) and had detectable mecA mutations (N146K, N204K, E150K and H351N). The ceftaroline yearly (2008) surveillance for the USA and Europe documented low MIC₅₀/₉₀ values for MRSA isolates at 1/1 and 1/2 mg/L, respectively. Ceftaroline demonstrated promising potency and coverage against Gram-positive and -negative pathogens known to cause cSSSIs, including MRSA and β-haemolytic streptococci.