Introduction: Ceftaroline (CPT) is a novel, parenteral, broad-spectrum cephalosporin exhibiting bactericidal activity against Gram-positive organisms, including methicillin-resistant S. aureus (MRSA) and multidrug-resistant S. pneumoniae (MDRSP) and common Gram-negative pathogens, including non-ESBL-producing Enterobacteriaceae (ENT). CPT is in late-stage development for treatment of complicated skin and skin structure infections (cSSSI) and community-acquired bacterial pneumonia. We evaluated the activity of CPT and comparator agents tested against cSSSI pathogens.

Methods: Unique (1 per patient) clinically significant isolates were consecutively collected from cSSSI in 25 USA medical centers in 2008-2009. Each medical center contributed approximately 50 strains each year and the most frequently isolated organisms were analyzed. Susceptibility (S) testing was performed by reference CLSI broth microdilution method (M07-A8; M100-S20) against CPT and numerous antimicrobials currently available for cSSSI treatment.

Results: More than 2,000 strains were tested and the 8 most common organisms are shown in the Table. The most frequently isolated organisms were MRSA (31.9%), methicillin-S S. aureus (MSSA; 27.8%) and E. coli (9.3%). 53.5% of S. aureus were MRSA. CPT was very active against MSSA and MRSA with highest MIC being 0.5 and 2 ?g/ml, respectively. CPT (MIC90, 1 ?g/ml; 100% inhibited at ≤2 ?g/ml), linezolid (MIC90, 2 ?g/ml; 100% S) and vancomycin (MIC90, 2 ?g/ml; 100% S) were the most active compounds tested against MRSA. Levofloxacin (LEV; 44% S) and clindamycin (80% S) showed limited activity against MRSA. CPT was 8-fold more potent than ceftriaxone (CRO) against MSSA. Against Enterobacteriaceae, CPT and CRO showed similar spectrum with 80-90% and 79-92% S rates, respectively (see Table). LEV showed variable activity against ENT species; only 69% of E. coli was LEV-S. P. aeruginosa (PSA) showed high resistance (R) rates to most antimicrobials; the most active agents were piperacillin/tazobactam (88% S) and imipenem (IMI; 89% S). PSA and CRO-R ENT generally exhibited elevated CPT MIC values.

Organism	MIC90 (µg/ml)/% Susceptible
(no. tested)	CPT	CRO	IMI	LEV
MRSA (656)	1/100a	>32/0	8/0	>4/44
MSSA (571)	.5/100a	4/>99	≤.12/100	2/92
ßHS (72)	.015/100a	≤.25/100	≤.12/100	1/100
EF (99)	4/80a	>32/NA	2/NA	>4/78
E. coli (190)	.2/90a	≤.25/92	.25/100	>4/69
KSP (93)	>16/85a	32/86	1/94	>4/88
ESP (94)	>16/80a	32/79	1/95	≤.5/99
PSA (118)	>16/3a	>32/2	>8/86	>4/73

a. % inhibited at ≤2 ?g/ml for CPT. NA = not applicable. ßHS = beta-haemolytic streptococci; EF = E. faecalis; KSP = Klebsiella spp., ESP = Enterobacter spp.
PSA = P. aeruginosa

Conclusions: CPT was highly active against Gram-positive and ENT pathogens recently isolated from cSSSI in USA medical centers, including MRSA. CPT spectrum against Gram-positive pathogens was similar to those of LZD and vancomycin; while against Gram-negative organisms CPT showed spectrum comparable to CRO. CPT appears to be a valuable agent for the treatment of organisms causing cSSSI.