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The postantibiotic effect and post‐β‐lactamase‐inhibitor effect of ceftazidime, ceftaroline and aztreonam in combination with avibactam against target Gram‐negative bacteria
Author(s) -
Pillar C.M.,
Stoneburner A.,
Shinabarger D.L.,
Krause K.M.,
Nichols W.W.
Publication year - 2016
Publication title -
letters in applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.698
H-Index - 110
eISSN - 1472-765X
pISSN - 0266-8254
DOI - 10.1111/lam.12592
Subject(s) - avibactam , aztreonam , beta lactamase inhibitors , klebsiella pneumoniae , microbiology and biotechnology , clavulanic acid , ceftazidime , cephalosporin , biology , sulbactam , ceftazidime/avibactam , chemistry , pseudomonas aeruginosa , bacteria , antibiotics , biochemistry , amoxicillin , gene , imipenem , escherichia coli , antibiotic resistance , genetics
The magnitudes of the postantibiotic effect ( PAE ) and post‐β‐lactamase‐inhibitory effect ( PLIE ) of ceftazidime‐avibactam, ceftaroline‐avibactam, and aztreonam‐avibactam were determined against isolates of Enterobacteriaceae and Pseudomonas aeruginosa that either harboured genes encoding serine and/or metallo‐β‐lactamases, or did not harbour bla genes. The bla genes included ones that encoded extended spectrum β‐lactamases, AmpC and KPC β‐lactamases, and one metallo‐β‐lactamase, NDM ‐1. No substantial PAE was observed for any combination against any isolate. One substantial PLIE was found: a value of 1·9 h for ceftazidime‐avibactam against Klebsiella pneumoniae ( bla KPC‐2 ). From comparison with results in the literature, we propose that the existence of a substantial PLIE depends on the bacterial isolate and on the specific β‐lactamase inhibitor and β‐lactam combination. Significance and Impact of the Study A wave of new β‐lactamase inhibitors is entering either therapeutic use or clinical trials. The present work characterizes the postantibiotic effect (PAE) and post‐β‐lactamase‐inhibitory effect (PLIE) of the clinically most advanced of these compounds, avibactam. We show that the existence of a measurable PLIE is strain‐ (and possibly compound‐) dependent, and cannot be relied upon as a standard component of the primary pharmacology of a new β‐lactamase inhibitor. This variability was not reported in earlier studies of clavulanic acid or sulbactam.