P-1500. Evaluation of Imipenem-cilastatin-relebactam for the Treatment of Infections Caused by Pseudomonas aeruginosa
Authors: Caniff Kaylee E , Xhemali Xhilda , Tran Nikki , Eubank Taryn A , Garey Kevin W , Guo Yi , Chang Mei H , Barber Katie , Biagi Mark , Carlson Travis J , Frens Jeremy J , Krekel Tamara , Veena Venugopalan , Kufel Wesley D , Carr Amy L , Hayes Jillian , Sanders James , Chandler Elisabeth , Li Rosanna , Justo Julie Ann , Antosz Kayla , Benefield Russell J , Moore William Justin , Ross Jennifer K , Hobbs Athena L V , Mercuro Nicholas , Raux Brian , Zeitler Kristen , Rybak Michael J 
Published: January 2025

Abstract

Background
The escalating prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa presents a serious threat to patient care due to its limited treatment options. However, imipenem-cilastatin-relebactam (IMI/REL) is a promising beta-lactam/beta-lactamase inhibitor combination with expanded activity against MDR P. aeruginosa. This study aimed to explore the patient characteristics, efficacy and safety of IMI/REL for treatment of infections due to P. aeruginosa.Table 1.Patient and infection characteristics.

Methods
This was a retrospective, observational, multicenter cohort study that included patients ≥ 18 years old who received IMI/REL for ≥ 48 hours for the treatment of an infection due to P. aeruginosa. The primary outcome was clinical success, defined as the resolution of or improvement in infectious signs and symptoms following initiation of IMI/REL until the end of therapy. Secondary outcomes included 30-day all-cause mortality, 30-day microbiologic recurrence, 30-day symptomatic recurrence and incidence of adverse drug reactions (ADRs).Table 2.Infection management and IMI/REL prescribing.

Results
There were 104 patients from nine U.S. medical centers included. The mean (standard deviation) age was 56.6 (17.2) years and the majority of patients were non-Hispanic Caucasian (64.4%). IMI/REL was predominantly used to treat lower-respiratory tract infections (55.7%) and 12.5% of cases developed secondary bacteremia. MDR P. aeruginosa was isolated in most patients (84.6%), while four patients (3.8%) were infected with a difficult-to-treat isolate. IMI/REL was initiated at a median (interquartile range) of 100.5 (44.8-170.3) hours from the time of index culture collection and was primarily selected due to the presence of resistance to alternative agents. Clinical success occurred in 73.1% of patients and 16.3% experienced 30-day all-cause mortality. Thirty-day microbiologic recurrence occurred in 14.4% of patients. ADRs occurred in six patients resulting in IMI/REL discontinuation in two cases.Table 3.Clinical outcomes.

Conclusion
To our knowledge, this is the largest report to date describing the use of IMI/REL for infections due to P. aeruginosa. The promising results herein justify the need for larger and comparative studies investigating the use of IMI/REL in this setting.

Disclosures
Kaylee E. Caniff, PharmD, BCIDP, T2Biosystems: Honoraria Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support Travis J. Carlson, PharmD, BCIDP, Aimmune Therapeutics, Inc.: Speakers Bureau Tamara Krekel, PharmD, BCPS, BCIDP, Merck Inc: Honoraria Wesley D. Kufel, Pharm.D., BCPS, BCIDP, Merck & Co.: Grant/Research Support|Shionogi, Inc: Grant/Research Support Amy L. Carr, PharmD, BCIDP, Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|Gilead: Advisor/Consultant|InflaRx: Advisor/Consultant|LaJolla: Advisor/Consultant|Melinta: Advisor/Consultant|MicroGenDx: Advisor/Consultant|Shionogi: Grant/Research Support Jillian Hayes, PharmD, BCIDP, GlaxoSmithKline: employee James Sanders, PhD, PharmD, Merck: Grant/Research Support|Shionogi: Grant/Research Support Julie Ann Justo, PharmD, MS, FIDSA, BCPS, Shionogi: Advisor/Consultant Russell J. Benefield, PharmD, BCPS-AQ ID, Paratek Pharmaceuticals: Grant/Research Support Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Advisor/Consultant|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Grant/Research Support|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Speaker