Antimicrobial activity of ceftaroline tested against staphylococci with reduced susceptibility to linezolid, daptomycin, or vancomycin from U.S. hospitals, 2008 to 2011

Abstract

Vancomycin, linezolid, and daptomycin are very active against staphylococci, but isolates with decreased susceptibility to these antimicrobial agents are isolated sporadically. A total of 19,350 Staphylococcus aureus isolates (51% methicillin resistant [MRSA]) and 3,270 coagulase-negative staphylococci (CoNS) were collected consecutively from 82 U.S. medical centers from January 2008 to December 2011 and tested for susceptibility against ceftaroline and comparator agents by the reference broth microdilution method. Among S. aureus strains, 14 isolates (0.07%) exhibited decreased susceptibility to linezolid (MIC, ≥ 8 μg/ml), 18 (0.09%) to daptomycin (MIC, ≥ 2 μg/ml), and 369 (1.9%) to vancomycin (MIC, ≥ 2 μg/ml; 368 isolates at 2 μg/ml and 1 at 4 μg/ml). Fifty-one (1.6%) CoNS were linezolid resistant (MIC, ≥ 8 μg/ml), and four (0.12%) were daptomycin nonsusceptible (MIC, ≥ 2 μg/ml). Ceftaroline was very active against S. aureus overall (MIC50/90, 0.5/1 μg/ml; 98.5% susceptible), including MRSA (MIC50/90, 0.5/1 μg/ml; 97.2% susceptible). All daptomycin-nonsusceptible and 85.7% of linezolid-resistant S. aureus isolates were susceptible to ceftaroline. Against S. aureus isolates with a vancomycin MIC of ≥ 2 μg/ml, 91.9, 96.2, and 98.9% were susceptible to ceftaroline, daptomycin, and linezolid, respectively. CoNS strains were susceptible to ceftaroline (MIC50/90, 0.25/0.5 μg/ml; 99.1% inhibited at ≤ 1 μg/ml), including methicillin-resistant (MIC50/90, 0.25/0.5 μg/ml), linezolid-resistant (MIC50/90, 0.5/0.5 μg/ml), and daptomycin-nonsusceptible (4 isolates; MIC range, 0.03 to 0.12 μg/ml) strains. In conclusion, ceftaroline demonstrated potent in vitro activity against staphylococci with reduced susceptibility to linezolid, daptomycin, or vancomycin, and it may represent a valuable treatment option for infections caused by these multidrug-resistant staphylococci.