Abstract

Abstract Background The 2022 IDSA Guidance on the Treatment of Antimicrobial-Resistant Gram-negative Infections recommends the use of a novel beta-lactam/beta-lactamase inhibitor, such as ceftolozane-tazobactam (C/T) or ceftazidime-avibactam (C/A), as first-line for treatment of resistant Pseudomonas aeruginosa infections. C/T is often preferred for these infections due to a narrower spectrum and lower cost. However, from December 2020 to January 2022, a global shortage of C/T resulted in widespread adoption of C/A as an alternative. While in vitro susceptibilities support the use of C/A for P. aeruginosa, real-world experience comparing clinical outcomes to C/T is limited. Methods This multicenter, retrospective analysis was conducted at an urban, academic healthcare system in the Bronx, NY. Between January 2018 and December 2020, admitted adult patients who received C/A or C/T to treat P. aeruginosa infections were included. Patients were excluded if in vitro resistance to either drug was demonstrated or if susceptibility was missing. The primary outcome was clinical success, defined as resolution of signs and symptoms of infection, by end of treatment. Secondary outcomes included 30-day mortality, resistance to study drug after therapy, modification of therapy, 14-day microbiological failure, 90-day infection recurrence, and length of stay. Results A total of 46 patients received C/A and 56 patients received C/T to treat P. aeruginosa infections. Most baseline characteristics were similar between the two arms, though more patients were critically ill in the C/A arm (Table 1). Clinical success was similar between C/A and C/T patients (72% vs. 63%, p=0.33). No significant differences between arms were identified for secondary outcomes (Table 2). Development of drug resistance within 90 days of treatment occurred more frequently in the C/A arm, approaching significance. On multivariate regression analysis, vasopressor use at the time of study drug initiation was the only variable associated with reduced clinical success. Conclusion C/A may be an effective alternative treatment for multidrug-resistant P. aeruginosa infections with close monitoring for development of resistance. Larger comparative studies are needed to confirm these findings. Disclosures Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support.

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