Activity of ceftaroline-avibactam tested against Gram-negative organism populations, including strains expressing one or more β-lactamases and methicillin-resistant Staphylococcus aureus carrying various staphylococcal cassette chromosome mec types.
Ceftaroline is a new cephalosporin with broad-spectrum activity against Gram-positive and -negative organisms. The prodrug of ceftaroline, ceftaroline fosamil, combined with the β-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 methicillin-resistant Staphylococcus aureus (MRSA) strains. Isolates were collected from 1999 to 2008 from global surveillance programs, and susceptibility testing was performed by reference broth microdilution methods. Ceftaroline-avibactam exhibited potent activity against Enterobacteriaceae producing various β-lactamase types (MIC(90), 0.25 to 2 μg/ml, except for metalloenzymes), including 99 strains carrying multiple enzymes (2 to 4 β-lactamases; MIC(90), 2 μg/ml). All isolates were inhibited by ceftaroline-avibactam at ≤4 μg/ml. Ceftaroline-avibactam (MIC(90), 0.5 to 1 μg/ml) was more active than meropenem (MIC(90), >8 μg/ml) and other comparators when tested against KPC-producing strains. S. aureus strains, including MRSA with four staphylococcal cassette chromosome mec (SCCmec) types, were dominantly (99.1%) inhibited by ceftaroline-avibactam at ≤2 μg/ml, and the ceftaroline MIC was not adversely affected by the addition of the β-lactamase inhibitor (MIC(50/90), 1 and 2 μg/ml for ceftaroline with and without avibactam). Ceftaroline-avibactam demonstrated limited activity against Acinetobacter spp. and P. aeruginosa (MIC(50)s, 32 and 16 μg/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 against those producing more than one of these β-lactamase types, and its development as a therapeutic option for the treatment of infections caused by multidrug-resistant Enterobacteriaceae as well as MRSA is warranted.
JMI Laboratories, North Liberty, Iowa, USA. mariana-castanheira@jmilabs.com
Mariana
M
Castanheira
Helio S
HS
Sader
David J
DJ
Farrell
Rodrigo E
RE
Mendes
Ronald N
RN
Jones
D000150:Acinetobacter / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D002876:Chromosomes, Bacterial; D004338:Drug Combinations; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D010957:Plasmids; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics; D000097583:Ceftaroline
D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D002511:Cephalosporins; D004338:Drug Combinations; D007527:Isoenzymes; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; D000097583:Ceftaroline; C543519:avibactam