Activity Analyses of Staphylococcal Isolates From Pediatric, Adult, and Elderly Patients: AWARE Ceftaroline Surveillance Program

Abstract

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a broad-spectrum cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), and common Gram-negative organisms. We evaluated the activity of ceftaroline and various antimicrobial agents against S. aureus isolates according to patient age. A total of 2143 consecutive unique patient strains of clinical significance were collected between January and December 2010 from 65 US medical centers as part of the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Program. Ceftaroline and various comparator agents were tested by reference Clinical and Laboratory Standards Institute broth microdilution methods. Ceftaroline was consistently active against methicillin-susceptible S. aureus (MSSA) (MIC(50), 0.25 μg/mL; MIC(90), 0.25 μg/mL; 100.0% susceptible) and MRSA (MIC(50), 0.50 μg/mL, MIC(90), 1 μg/mL; 98.4% susceptible) from all age groups. In general, resistance rates to erythromycin, clindamycin, and levofloxacin were higher in the population aged ≥ 65 years, whereas resistance rates to clindamycin and levofloxacin were lowest among isolates from patients aged 6-17 years. When tested against MSSA, levofloxacin resistance was higher among isolates from patients aged ≥ 65 years (16.1%) than among isolates from the other age groups (6.1%-10.5%), and ceftaroline was generally 16-fold more active than ceftriaxone (MIC(50), 4 μg/mL; MIC(90), 4 μg/mL; 97.9% susceptible overall). Ceftaroline (MIC(50), 0.50 μg/mL; MIC(/90), 1 μg/mL), daptomycin (MIC(50), 0.25 μg/mL; MIC(90), 0.5 μg/mL), linezolid (MIC(50), 1 μg/mL; MIC(90), 1 μg/mL), and vancomycin (MIC(50), 1 μg/mL(;) MIC(90), 1 μg/mL) were the most active compounds tested against MRSA strains, and the activity of these compounds did not vary significantly among the age groups. In contrast, susceptibility rates to clindamycin and levofloxacin varied from 94.0% and 60.7% (aged 6-17 years), respectively, to only 57.6% and 15.1% (aged ≥ 65 years), respectively, among MRSA strains. The results of this study showed major differences in the susceptibility rates to clindamycin and levofloxacin according to patient age group. The results also indicate that ceftaroline is highly active against MSSA and MRSA isolated from US medical centers, independent of patient age group.