Abstract
Background
Ceftazidime/avibactam (CZA) and ceftolozane-tazobactam (CT) are new additions to the antibiotic armamentarium with activity against gram-negative pathogens, most notably drug-resistant Pseudomonas aeruginosa (PSA). The purpose of this study was to compare the in vitro activity of CZA and CT against a large real-world sample of clinical isolates of PSA displaying different phenotypes of resistance to conventional β-lactams at an institution where both CZA and CT are routinely tested on all isolates.
Methods
All cultures from patient infections with PSA from May 2018 to February 2019 at Michigan Medicine were included. Minimum inhibitory concentrations (MICs) for all β-lactams were determined using TREK broth microdilution panels and isolates were considered susceptible to CZA if the MIC was ≤8 mg/L and CT if the MIC was ≤4 mg/L.
Results
A total of 2,972 isolates of PSA from clinical specimens were included. Table 1 compares CZA and CT susceptibility, MIC50, MIC90, and MIC range for all isolates including those displaying resistance to various β-lactams. Among all isolates of PSA, CZA (96.2% susceptible) was slightly more active than CT (94.2%) and both agents were ~10% more active than the closest comparator (ceftazidime, 86.6%). In vitro activity of cefepime, piperacillin/tazobactam, and meropenem were 84.8%, 78%, and 80.3%, respectively. The activity of both CZA and CT dropped significantly among isolates with pan-β-lactam resistance (i.e., resistance to all conventional anti-pseudomonal β lactams, PBR) but CZA remained more active than CT (59.4% vs. 41.5%, P < 0.001). Of isolates displaying resistance to CT, 84 (48.6%) were susceptible to CZA. However, of those with resistance to CZA, only 24 (21.2%) were susceptible to CT (Table 2).
Conclusion
CZA was the most active β-lactam against PSA isolates at Michigan Medicine. Among PSA with PBR, CZA demonstrated superior activity compared with CT. Additionally, a significant number of isolates with resistance to CT were susceptible to CZA. Our findings are unique compared with other published reports where CT has consistently demonstrated greater activity than CZA against resistant P. aeruginosa and suggest routine testing of both CT and CZA should occur.
Disclosures
All authors: No reported disclosures.
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