Introduction: Ceftaroline (CPT) is a novel, parenteral, broad-spectrum cephalosporin exhibiting bactericidal activity against Gram-positive organisms, including MRSA and multidrug-resistant Streptococcus pneumoniae (MDRSP), as well as common Gram-negative pathogens. CPT is in late-stage clinical development for treatment of complicated skin and skin structure infections (cSSSI) and community-acquired bacterial pneumonia. S. aureus is the main cause of cSSSI. We assessed the activity of CPT tested against S. aureus from USA hospitals.

Methods: 6,626 unique clinical S. aureus strains, consecutively collected from 40 USA medical centers in 2008-2009, plus 10 molecularly characterized USA300-0114 strains (from cSSSI) were tested for susceptibility (S) against CPT and various comparator agents by CLSI broth microdilution methods.

Results: 53.4% of S. aureus were MRSA. CPT was very active against methicillin-S strains (MSSA) and MRSA with MIC90s of 0.25 and 1 ?g/ml, respectively. All MRSA were inhibited at ≤2 ?g/ml of CPT (see Table). CPT was eight- to 16-fold more potent than ceftriaxone (MIC50/90, 4/4 ?g/ml) and cefepime (MIC50/90, 2/4 ?g/ml) against MSSA. MRSA showed high resistance rates to erythromycin (92.5%), levofloxacin (71.3%) and clindamycin (34.7%), but remained 100.0% S to linezolid (MIC50/90, 2/2 ?g/ml), vancomycin (MIC50/90, 1/1 ?g/ml) and daptomycin (MIC50/90, 0.25/0.5 ?g/ml). CPT was four- to eight-fold more active than linezolid or vancomycin and showed activity similar to daptomycin when tested against MRSA. All USA300-0114 strains were PVL positive, had SCCmec type IVa and were highly CPT-S (MIC range, 0.5-1 ?g/ml).

Organism	Cumulative % inhibited at CPT MIC of:
(no.)	≤.06	.12	.25	.5	1	2
MSSA (3,089)	0.8	6.4	90.3	99.8	100	-
MRSA (3,537)	0.0	0.1	1.4	40.6	95.2	100
USA300 (10)	0.0	0.0	0.0	50.0	100	-

Conclusions: CPT was highly active against a large collection of MSSA and MRSA strains recently isolated in USA hospitals, including representative strains of the pandemic USA300 clone. CPT represents a very promising therapeutic option for treatment of cSSSI infections, including those caused by MRSA.