Antimicrobial Activity of Ceftazidime-Avibactam Tested Against Pseudomonas aeruginosa Isolates from USA Hospitals Stratified by Site of Infection: Results from the INFORM Surveillance Program, 2013-2015

Background: Ceftazidime (CAZ)-avibactam (AVI) was approved by the United States (US) Food and Drug Administration (FDA) for treatment of complicated intra-abdominal and urinary tract infections in 2015 and is under clinical development for treatment of hospital-acquired pneumonia.

Methods: 5,486 P. aeruginosa (PSA) isolates (one per patient) were consecutively collected in 2013-2015 from 77 USA medical centers (37 states from all 9 census regions) by the INFORM Surveillance Program. CAZ-AVI (AVI at fixed 4 µg/mL) and comparators were tested for susceptibility (S) by CLSI broth microdilution methods and results were stratified by infection type.

Results: Isolates were mostly from pneumonia (n=2,903; 52.9%), skin/soft tissue (SSSI; 1,286; 23.4%), bloodstream (BSI; 436; 7.9%), urinary tract (UTI; 417; 7.6%) and intra-abdominal infections (IAI; 199; 3.6%). Overall, CAZ-AVI was active against 97.0% of isolates at the US-FDA S breakpoint of ≤8 µg/mL, while S rates for meropenem (MEM), piperacillin-tazobactam (PT) and amikacin (AMK) were 82.0%, 81.3% and 96.8%, respectively (Table). When stratified by infection type, CAZ-AVI S rates varied from 95.6% (BSI) to 98.2% (SSSI), whereas S rates for MEM varied from 78.9% (pneumonia) to 87.1% (SSSI). The occurrences of multidrug-resistance (MDR) and extensively drug-resistance (XDR) were highest among isolates from pneumonia (18.2 and 10.7%, respectively) and UTI (14.9 and 9.6%, respectively), and CAZ-AVI was active against 81.9 and 74.6% of MDR and XDR isolates, respectively. In contrast, S rates for MEM and PT were only 20.5 and 17.8% among MDR and 7.0 and 6.4% among XDR isolates, respectively. High rates of cross-resistance were observed among MEM, PT and CAZ; while CAZ-AVI retained good in vitro activity against PSA isolates that were not S to MEM, PT and CAZ, inhibiting 69.9% at ≤8 µg/mL.

Conclusion: CAZ-AVI exhibited potent in vitro activity and spectrum when tested against a large collection (n=5,486) of recent PSA clinical isolates. CAZ-AVI was consistently active against PSA isolates from all infection types and retained activity against isolates not S to other anti-PSA β-lactams, as well as MDR and XDR strains.