Antimicrobial Activity of Ceftaroline Tested Against Common Pathogens Causing Complicated Skin and Soft Tissue Infections in European Medical Centres in 2009

≤0.008 0.015 0.03 0.06 0.12 0.25 0.5 1 2 S. aureus (1985) 1 (0.1) 0 (0.1) 0 (0.1) 13 (0.7) 145 (8.0) 1240 (70.5) 306 (85.9) 200 (96.0) 80 (100.0) MSSA (1496) 1 (0.1) 0 (0.1) 0 (0.1) 13 (0.9) 145 (10.6) 1227 (92.7) 108 (99.9) 2 (100.0) - MRSA (489) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 13 (2.7) 198 (43.2) 198 (83.6) 80 (100.0) Abstract Objective: To assess the activity of ceftaroline and comparator agents tested against pathogens responsible for complicated skin and soft tissue infections (cSSTI). Ceftaroline, the active component of the prodrug ceftaroline fosamil, demonstrates bactericidal activity against Gram-positive organisms, including methicillin-resistant S. aureus (MRSA), and common Gram-negative pathogens associated with cSSTI. Methods: Clinically significant, unique (1 per patient) isolates of S. aureus (n=1985; 24.6% MRSA) and b-haemolytic streptococci (BHS; n=388) were collected consecutively from 27 medical centres in 11 European (EU) countries, Turkey and Israel in 2009. Isolates were tested and interpreted for susceptibility (S) by CLSI broth microdilution methods (M07-A8; M100-S21) to ceftaroline and numerous comparator antimicrobials currently available for cSSTI treatment. Results: Ceftaroline was very active against all S. aureus (24.6% MRSA; highest MIC, 2 mg/L). Oxacillin-S S. aureus (MSSA; MIC50 and MIC90, 0.25 mg/L) had lower MICs than MRSA (MIC50/90, 1/2 mg/L). Against MSSA, ceftaroline was 2-, 4-, 8-, 16- and 16-fold more potent than daptomycin (DAP), vancomycin (VAN), linezolid (LZD), ceftriaxone (CRO) and cefepime (CPM), respectively. MRSA isolates demonstrated 100.0% S to LZD, VAN, DAP and tigecycline, but high resistance to levofloxacin (LEV; 89.4%), erythromycin (ERY; 65.6%) and clindamycin (CLI; 32.1%). Against BHS, all isolates were inhibited at ≤0.03 mg/L of ceftaroline, with the greatest activity (MIC90) observed against group A (≤0.008 mg/L), followed by other BHS (0.015 mg/L) and group B (0.03 mg/L). Ceftaroline was 8-, 16-, 32- and 32-fold more potent than DAP, VAN, LZD and LEV, respectively, against BHS. The lowest S rates among BHS isolates were observed against CLI (90.2%) and ERY (82.5%).