The postantibiotic effect and post-ß-lactamase-inhibitor effect of ceftazidime, ceftaroline and aztreonam in combination with avibactam against target Gram-negative bacteria.

UNLABELLED: The magnitudes of the postantibiotic effect (PAE) and post-ß-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-ß-lactamases, or did not harbour bla genes. The bla genes included ones that encoded extended spectrum ß-lactamases, AmpC and KPC ß-lactamases, and one metallo-ß-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 (blaKPC-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 ß-lactamase inhibitor and ß-lactam combination. SIGNIFICANCE AND IMPACT OF THE STUDY: A wave of new ß-lactamase inhibitors is entering either therapeutic use or clinical trials. The present work characterizes the postantibiotic effect (PAE) and post-ß-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 ß-lactamase inhibitor. This variability was not reported in earlier studies of clavulanic acid or sulbactam.