In vitro Activity of Ceftaroline and 11 Comparators against Pediatric Staphylococcus aureus and Pneumococcal isolates from 2007-2013, Focusing on Invasive and Antibiotic Resistant Strains

Background: Ceftaroline (CPT) is a parenteral cephalosporin FDA approved for adult use. It has bactericidal activity against Staphylococcus aureus (SA), both methicillin resistant (MRSA) and methicillin susceptible (MSSA), and pneumococci (SPN), including multi-drug resistant (MDR) 19A strains. To expand data on pediatric isolates, we assayed in vitro MICs of CPT for pediatric MSSA, MRSA and SPN.

Methods: From a repository with 1240 non-duplicate SA and SPN strains isolated at Children’s Mercy Hospitals from pediatric patients during 2007-2013, 416 isolates have been tested to date. Susceptibility was assayed by CLSI broth microdilution testing against CPT and 11 comparators specific for each species. All SPN were serotyped by the Quellung method. For CPT, SA were considered susceptible at ≤1.0 μg/mL and SPN at ≤0.25 μg/mL per FDA breakpoints.

Results: Clindamycin resistant SA made up nearly 20% of both MSSA and MRSA, with most clindamycin resistant MSSA being D test positive. Among tested SA, CPT had MIC50/90 of 0.25/1 μg/mL. CPT MIC50/90 values for MRSA were higher than for MSSA (0.5/1 μg/mL vs. 0.25/0.5 μg/ml). For 230 invasive SA (63% MSSA), all were susceptible to vancomycin and linezolid; and 95% were susceptible to trimethoprim/sulfa. Among all SA (52% MRSA), MIC50/90 for linezolid was 1/2 μg/mL, for levofloxacin 0.25/4 μg/mL and for tetracycline 0.5/1 μg/mL.

Among SPN, 34% had penicillin MIC ≥2 μg/mL and 19% had penicillin MIC >0.1 but <2.0 μg/mL; 22% were ceftriaxone-nonsusceptible. All were vancomycin susceptible. For 186 SPN overall, CPT had MIC50/90 of <0.06/0.25 μg/mL. CPT MIC50/90 values were <0.06/0.125 μg/mL for clindamycin resistant and 0.25/0.5 μg/mL for ceftriaxone non-susceptible strains. Against penicillin-resistant SPN (≥2 μg/mL), MIC50/90 for CPT was 0.25/0.5 μg/mL, compared to 2/4 μg/mL for ceftriaxone, 4/8 μg/mL for cefuroxime, and 8/16 μg/mL for amoxicillin. Among the 69 serogroup-19 strains, MIC50/90 for CPT was 0.125/0.25 μg/mL.

Conclusion: Against pediatric invasive SA isolates, CPT has potent in vitro activity vs. MRSA and MSSA, including isolates resistant to clindamycin, tetracycline or levofloxacin. CPT also has consistent activity against pediatric SPN including MDR serotype 19A strains.