587. Antimicrobial Activity of Ceftaroline/NXL104 Tested Against Contemporary (2010) Clinical Isolates from USA Medical Centers
Session: Poster Abstract Session: Novel Antimicrobial Agents
Friday, October 21, 2011
Room: Poster Hall B1

Background: Ceftaroline (CPT), the active form of CPT fosamil, is a broad-spectrum, bactericidal cephalosporin active against Gram-positive (including MRSA and multidrug-resistant [R] S. pneumoniae [SPN]) and common Gram-negative organisms. NXL104 (NXL) is a novel non-β-lactam β-lactamase inhibitor of Ambler class A, C, and D enzymes. We evaluated the activity and potency of CPT/NXL (CPT104) against recent clinical isolates.

Methods: Isolates were consecutively collected in 2010 from 65 USA medical centers from all 9 CDC Census Regions (5-10/region). Susceptibility (S) testing for CPT104 (NXL at fixed 4 mg/ml), CPT and comparators was performed by CLSI broth microdilution on 8434 strains.

Results: For MSSA and MRSA, all strains were inhibited at ≤0.5 and ≤2 mg/mL of CPT104, respectively (Table), and CPT MICs were not impacted by the addition of NXL. Penicillin (PEN)-R (MIC50/90, 0.25/0.25 mg/mL) and levofloxacin-non-S (MIC50/90, ≤0.03/0.25 mg/mL) SPN were CPT104-S. CPT104 was 8- to 16-fold more active than ceftriaxone against MSSA and PEN-R SPN; the highest CPT104 MIC value was only 0.5 mg/mL for both organisms. Against H. influenzae, the highest CPT104 MIC value was 0.06 mg/ml (MIC90, ≤0.03 mg/ml). β-haemolytic and viridans group streptococci were CPT104-S with MIC90s of 0.015 and 0.12 mg/mL, respectively. All E. coli, including ESBL-producing strains, were inhibited at CPT104 MIC values of ≤0.5 mg/mL. CPT104 was also active against H. influenzae (MIC90 ≤0.03 mg/mL), Klebsiella spp. (MIC90, 0.12 mg/mL), including ESBL-phenotype and meropenem-non-S strains (MIC90, 1 mg/mL for both subsets) and M. morganii (MIC90 0.12 mg/mL).

Conclusion: CPT104 and CPT were the most potent β-lactam agents tested against staphylococci and streptococci collected from USA hospitals. MRSA and PEN-R-SPN were particularly S to CPT104 and CPT (data not shown). CPT104 was also highly active against Enterobacteriaceae producing KPC, various ESBL types, and AmpC (chromosomal or plasmid mediated) enzymes. CPT104 represents a potential therapeutic option for infections caused by these R organisms.


Subject Category: A. Antimicrobial agents and Resistance

Helio S. Sader, M.D., Ph.D.1, David J. Farrell, Ph.D.1, Gary J. Moet1, Gregory Williams2 and Ronald Jones, MD1, (1)Microbiology, JMI Laboratories, North Liberty, IA, (2)Cerexa Inc. (a wholly-owned subsidiary of Forest Laboratories Inc.), Oakland, CA

Disclosures:

H. S. Sader, None

D. J. Farrell, None

G. J. Moet, None

G. Williams, Cerexa, Inc.: Employee, Salary

R. Jones, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.