In Vitro Antibacterial Activity of the Ceftazidime-Avibactam (NXL104) Combination against Pseudomonas aeruginosa Clinical Isolates

The -lactamase inhibitor avibactam (NXL104) displays potent inhibition of both class A and C enzymes. The in vitro antibacte-rial activity of the combination ceftazidime-avibactam was evaluated against a clinical panel of Pseudomonas aeruginosa iso-lates. Avibactam offered efficient protection from hydrolysis since 94 % of isolates were susceptible to ceftazidime when com-bined with 4g/ml avibactam, compared with 65 % susceptible to ceftazidime alone. Ceftazidime-avibactam also demonstrated better antipseudomonal activity than imipenem (82 % susceptibility), a common reference treatment. Pseudomonas aeruginosa is a major opportunistic pathogen fre-quently involved in hospital-acquired infections that may be resistant to many classes of antimicrobial agents. The expression of the naturally occurring chromosomal AmpC -lactamase, as well as acquired extended-spectrum -lactamases (ESBLs), strongly limits the susceptibility of P. aeruginosa isolates to peni-cillins, such as piperacillin, and cephalosporins, such as ceftazi-dime. In addition,most of these enzymes are only poorly inhibited by the-lactamase inhibitors clavulanic acid and tazobactam. Re-sistance to imipenem is also common and is frequently associated with the loss of functional OprD outer membrane protein and