Ceftaroline Activity Against Multidrug-Resistant Streptococcus pneumoniae from U.S. Medical Centers (2014) and Molecular Characterization of a Single Ceftaroline Nonsusceptible Isolate

Abstract

Streptococcus pneumoniae isolates (2,614) were collected from patients at 135 U.S. Medical Centers during 2014. Isolates were evaluated for multidrug resistance to penicillin, ceftriaxone, erythromycin, tetracycline, trimethoprim–sulfamethoxazole, and levofloxacin. A single isolate (853008) demonstrated a ceftaroline nonsusceptible minimal inhibitory concentration (MIC) value, and it was subjected to molecular characterization. Ceftaroline (MIC_50/90, ≤0.015/0.12 μg/ml) was eightfold more potent than ceftriaxone (MIC_50/90, ≤0.06/1 μg/ml) against all isolates. For multidrug-resistant (MDR) isolates (28.8% of tested strains), ceftaroline (MIC_50/90, 0.06/0.25 μg/ml; 99.9% susceptible) was the most active agent tested, being eightfold more active than ceftriaxone (MIC_50/90, 0.25/2 μg/ml; 81.5% susceptible at MIC, ≤1 μg/ml) and 16-fold more active than penicillin (MIC_50/90, 0.25/4 μg/ml; 78.5% susceptible at MIC, ≤2 μg/ml). Isolate 853008 was a single locus variant of sequence type 377 and serotype 35B. It had multiple substitutions in the penicillin-binding proteins (PBPs), mainly PBP2x, when compared with reference sequences from the R6 strain. Isolate 853008 showed 31 amino acid alterations in MurM. The in vitro data presented here confirm that ceftaroline potency against S. pneumoniae to be higher than other β-lactams, including against those isolates demonstrating ceftriaxone nonsusceptible and MDR phenotypes.