In vitro activity of ceftaroline and comparator antimicrobials against European and Middle East isolates from complicated skin and skin-structure infections collected in 2008-2009

The activities of ceftaroline, the active metabolite of the pro-drug ceftaroline fosamil, a novel anti-meticillin-resistant staphylococcal cephalosporin, and nine comparators were determined against surveillance isolates collected in 2008-2009. Over 3000 isolates associated with complicated skin and skin-structure infections (cSSSIs) were collected from 106 centres in 19 countries. MICs were determined using CLSI broth microdilution methodology. Clonal relatedness of meticillin-resistant Staphylococcus aureus (MRSA) with raised ceftaroline MICs (2 mg/L) was assessed by MLST, PFGE and mec typing. The presence of Panton-Valentine leukocidin in these isolates was also determined. Ceftaroline was active against 500 MRSA and 479 meticillin-susceptible S. aureus, with MIC50/90 values of 0.5/2 mg/L and 0.25/0.25 mg/L, respectively. For coagulase-negative staphylococci (CoNS), the ceftaroline MIC50/90 values for meticillin-resistant strains (n = 159) were the same as those seen for MRSA. Meticillin-susceptible CoNS (n = 113) had the same MIC90 as that seen with S. aureus, but the MIC50 was lower at 0.06 mg/L. Ceftaroline was also active against β-haemolytic streptococci (n = 526; MIC50/90 = 0.004/0.015 mg/L), other streptococci (n = 75; 0.015/0.06 mg/L), common Enterobacteriaceae (n = 897; 0.25/≥128 mg/L) and Enterococcus faecalis (n = 329; 1/16 mg/L). Those MRSA with ceftaroline MICs of 2 mg/L were found to be from four clonal groups associated with the country of origin. These data confirm the broad-spectrum in vitro activity of ceftaroline against cSSSI pathogens. Ceftaroline is unique among clinically available cephalosporins, having good in vitro activity against MRSA and meticillin-resistant CoNS and moderate activity against Gram-negative bacteria.