Ceftaroline Activity Tested against Bacterial Isolates from Pediatric Patients: Results from the Assessing Worldwide Antimicrobial Resistance and Evaluation (AWARE) Program for the United States (2011-2012)

Background: Ceftaroline (CPT), the active form of CPT fosamil, is a cephalosporin with broad-spectrum bactericidal activity against resistant (R) gram-positive (GP) organisms, including methicillin-R S. aureus (MRSA), and many Enterobacteriaceae species. CPT fosamil is FDA-approved for treatment of acute bacterial skin/skin structure infections and community-acquired bacterial pneumonia in adults.

Methods: 5291 consecutive unique pediatric patient strains of clinical significance were collected from 157 USA medical centers as part of the AWARE Program. The isolates were identified locally and forwarded to a central monitoring laboratory (JMI Laboratories) for reference antimicrobial susceptibility (S) testing. S results were analyzed according to patient age as follows: ≤1 years old (yo; 1857 strains); 2-5 (1342); 6-12 (1281) and 13-17 (811).

Results: MRSA rates were slightly lower in isolates from patients 13-17 yo (39.9%) compared to other age groups, and CPT was consistently active against S. aureus (SA) isolates from all four age groups (MIC_50/90, 0.25/1 µg/mL; 99.8-100.0% S). 99.8% of MRSA were CPT-S (MIC_50/90, 0.5/1 µg/mL). R rates to erythromycin, clindamycin and levofloxacin among SA did not vary significantly among age groups. All S. pneumoniae (SPN) strains (1178) were CPT-S (MIC_50/90, ≤0.015/0.12 µg/mL), while ceftriaxone S varied from 84.8 (≤1 yo) to 89.7% (13-17 yo). The highest CPT MIC among H. influenzae (HI; 587 strains) was 0.12 µg/mL (100.0% S), and β-lactamase production rates varied from 24.2 (13-17 yo) to 30.1% (6-12 yo); 27.9% overall. CPT was also very active against β-hemolytic streptococci (BHS; 556 strains, highest MIC 0.06 µg/mL). ESBL-phenotype rates among E. coli (EC)/Klebsiella spp. (KSP) were 6.0/5.1, 11.0/11.5, 5.1/8.3 and 11.4/14.7% for the ≤1, 2-5, 6-12 and 13-17 age groups, respectively. CPT exhibited good activity against non-ESBL-phenotype strains of EC and KSP (MIC₉₀, 0.25 µg/mL for both organisms), but limited activity against ESBL-producing strains.

Conclusion : CPT demonstrated potent in vitro activity against SA, SPN, BHS and HI isolated from pediatric patients, independent of patient age. Differences in S rates to comparator agents according to patient age group were observed mainly among EC and KSP.