In vitro activity of ceftaroline against multidrug-resistant Staphylococcus aureus and Streptococcus pneumoniae: a review of published studies and the AWARE Surveillance Program (2008-2010)

David J Farrell, Mariana Castanheira, Rodrigo E Mendes, Helio S Sader, Ronald N Jones
Clinical Infectious Diseases 2012, 55: S206-14
Ceftaroline is a new broad-spectrum parenteral cephalosporin with antibacterial activity against the prevalent pathogens causing both acute bacterial skin and skin structure infections (ABSSSIs) and community-acquired bacterial pneumonia (CABP). The Assessing Worldwide Antimicrobial Resistance Evaluation Surveillance Program was conducted in the United States between 2008 and 2010 to assess the in vitro activity of ceftaroline and comparator antibacterial agents against ABSSSI and CABP pathogens. A total of 8469 Staphylococcus aureus isolates and 3593 Streptococcus pneumoniae isolates collected from 72 medical centers representing all US Census regions were submitted to a central reference laboratory (JMI Laboratories, North Liberty, IA) for broth microdilution testing by reference methods. The overall prevalence of methicillin resistance among S. aureus isolates was 52.6%, and although ceftaroline showed more potent activity against methicillin-susceptible S. aureus (minimum inhibitory concentration for 50% [MIC(50)] and 90% [MIC(90)] of organisms, both 0.25 µg/mL) than against methicillin-resistant S. aureus (MIC(50) and MIC(90), both 1 µg/mL), it showed good activity against all 8469 S. aureus isolates (MIC(50) and MIC(90), 0.5 and 1 µg/mL, respectively), with 8296 isolates (98.0%) testing susceptible at the US Food and Drug Administration (FDA) break point of ≤ 1 µg/mL and no isolates having MICs of >2 µg/mL. Against S. pneumoniae, ceftaroline inhibited 98.7% of tested isolates at the FDA susceptible break point of ≤ 0.25 µg/mL (MIC(50) and MIC(90), 0.015 and 0.12 µg/mL, respectively) and was 16-fold more active than ceftriaxone (MIC(90), 2 µg/mL). The prevalence of multidrug resistance among S. pneumoniae isolates was 30.1% overall and remained stable over each of the 3 monitored years. Ceftaroline demonstrated high activity (MIC(50) and MIC(90), 0.12 and 0.25 µg/mL, respectively) against multidrug-resistant S. pneumoniae, with only 44 of 1001 strains (4.4%) testing nonsusceptible and all 44 nonsusceptible strains having a ceftaroline MIC of only 0.5 µg/mL. Ceftriaxone resistance among S. pneumoniae was 2.1% (10.9% were nonsusceptible), with an intermediate susceptibility rate of 8.8%, resulting in an overall susceptibility rate of only 89.1%. Ceftaroline surveillance in the United States during 2008-2010 documented sustained potency and spectrum against multidrug-resistant S. aureus and multidrug-resistant S. pneumoniae known to cause ABSSSI and CABP.

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