Susceptibility Profiles of Ceftolazane-Tazobactam (C-T) and Ceftazidime-Avibactam (CZA) Against Isolates of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa

Abstract

Background. Nosocomial infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas are increasing in frequency and are difficult to treat. The newer cephalosporin-beta-lactamase inhibitor combinations, C-T and CZA have demonstrated activity against Pseudomonas aeruginosa isolates with activity against isolates resistant to ceftazidime alone or piperacillin-tazobactam. Both cephalosporin-beta-lactamase inhibitor antibiotics C-T and CZA are currently approved for use with complicated intra-abdominal infections with addition of metronidazole or complicated urinary tract infections, including pyelonephritis, though use for other indications is not currently approved by the FDA. Published articles showcasing C-T have reported successful treatment of lower respiratory tract infections in off-label use where MDR Pseudomonas aeruginosa was isolated. Methods. Susceptibility testing was performed using E-test agar diffusion methods for 35 clinical isolates of MDR/XDR Pseudomonas aeruginosa and 1 reference strain of P. aeruginosa with testing against all 36 isolates against C-T and 35 against CZA. Twenty-two organisms were isolated from respiratory secretions, 6 from wounds not from an intra-abdominal source, 5 from urine, and 2 from blood. Twenty were classified as MDR while 15 were XDR. Breakpoints for susceptibility include susceptible at ≤ 4/4, intermediate at 8/4 and resistant at >16/4 for C-T, and susceptible at ≤ 8/4, and resistant at >16/4 for CZA. Results. The modal MIC for C-T was 0.75 mcg/mL and for CZA was 2 mcg/mL. The MICs at which 90% of the isolates tested were inhibited (MIC90) for C-T was ≥128 and for CZA was 32 63% of isolates demonstrated susceptibility to C-T at ≤ 4/ 4, while 76% of isolates were susceptible to CZA at ≤ 8/4. Conclusion. Results of antimicrobial agent testing demonstrate the potential of CT and CZA to treat susceptible isolates of MDR/XDR Pseudomonas. Results support consideration of these agents as an option to treat respiratory tract infections where extensive resistance leaves no alternative for standard antimicrobial intervention and where use of colistin is not advised or the organism is resistant.