title: 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 (MIC50/90, ≤0.015/0.12 μg/ml) was eightfold more potent than ceftriaxone (MIC50/90, ≤0.06/1 μg/ml) against all isolates. For multidrug-resistant (MDR) isolates (28.8% of tested strains), ceftaroline (MIC50/90,0.06/0.25 μg/ml; 99.9% susceptible) was the most active agent tested, being eightfold more active than ceftriaxone (MIC50/90, 0.25/2 μg/ml; 81.5% susceptible at MIC, ≤1 μg/ml) and 16-fold more active than penicillin (MIC50/90, 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.
authors.affiliation: 1 JMI Laboratories , North Liberty, Iowa.|2 University of Iowa , Iowa City, Iowa.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pfaller
authors.affiliation: 1 JMI Laboratories , North Liberty, Iowa.
authors.forename: Rodrigo E
authors.initials: RE
authors.lastname: Mendes
authors.affiliation: 1 JMI Laboratories , North Liberty, Iowa.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.affiliation: 1 JMI Laboratories , North Liberty, Iowa.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.affiliation: 1 JMI Laboratories , North Liberty, Iowa.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
mesh_terms: D000046:Academic Medical Centers; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004917:Erythromycin / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D064704:Levofloxacin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D046915:Penicillin-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D010406:Penicillins / Q000494:pharmacology; D011018:Pneumonia, Pneumococcal / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology; D014481:United States / Q000453:epidemiology; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D002511:Cephalosporins; D004917:Erythromycin; D064704:Levofloxacin; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D013752:Tetracycline; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000097583:Ceftaroline
keywords: Streptococcus pneumoniae; antimicrobial; pneumococcal infections