Activity of Ceftaroline-Avibactam Tested Against Gram-negative Organism Populations, Including Strains Expressing One or More ÃÂ²-Lactamases and Methicillin-Resistant Staphylococcus aureus Carrying Various SCCmec Types.
Antimicrob Agents Chemother. 2012 Jun 25;
Authors: Castanheira M, Sader HS, Farrell DJ, Mendes RE, Jones RN
Ceftaroline is a new cephalosporin with broad-spectrum activity against Gram-positive and -negative organisms. The prodrug of ceftaroline, ceftaroline fosamil, combined with the ÃÂ²-lactamase inhibitor avibactam (formerly NXL104) was tested against Enterobacteriaceae strains producing Ambler class A, B, C, and D enzymes, including strains producing multiple enzymes, as well as Pseudomonas aeruginosa, Acinetobacter spp. and methicillin-susceptible and -resistant (MRSA) Staphylococcus aureus strains. Isolates were collected from 1999-2008 from global surveillance programs and susceptibility testing was performed by reference broth microdilution methods. Ceftaroline-avibactam exhibited potent activity against Enterobacteriaceae producing various ÃÂ²-lactamase types (MIC(90), 0.25 to 2 ÃÂ¼g/ml; except metallo-enzymes), including 99 strains carrying multiple enzymes (2 to 4 ÃÂ²-lactamases; MIC(90), 2 ÃÂ¼g/ml). All isolates were inhibited by ceftaroline-avibactam at Ã¢ÂÂ¤4 ÃÂ¼g/ml. Ceftaroline-avibactam (MIC(90), 0.5-1 ÃÂ¼g/ml) was more active than meropenem (MIC(90), >8 ÃÂ¼g/ml) and other comparators when tested against KPC-producing strains. S. aureus strains, including MRSA with four SCCmec types, were dominantly (99.1%) inhibited by ceftaroline-avibactam at Ã¢ÂÂ¤2 ÃÂ¼g/ml and the ceftaroline MIC was not adversely affected by the addition of the ÃÂ²-lactamase inhibitor (MIC(50/90), 1 and 2 ÃÂ¼g/ml for ceftaroline with and without avibactam). Ceftaroline-avibactam demonstrated limited activity against Acinetobacter spp. and P. aeruginosa (MIC(50), 32 and 16 ÃÂ¼g/ml, respectively). These results document that ceftaroline-avibactam has potent activity against Enterobacteriaceae that produce KPC, various ESBL types (CTX-M types), and AmpC (chromosomally derepressed or plasmid mediated enzymes), as well as those producing more than one of these ÃÂ²-lactamase types and its development as therapeutic option for treatment of infections caused by multidrug-resistant Enterobacteriaceae as well as MRSA is warranted.
PMID: 22733066 [PubMed - as supplied by publisher]Link to Article at PubMed