1623. Outcomes of Critically Ill Adults, Hospitalized Patients (Pts) with Pseudomonas aeruginosa (PSA) Hospital- and Ventilator-Associated Pneumonia (HAP/VAP) Who Received an Active Anti-Pseudomonal β-Lactam (ASPB): Does “S” Equal Success in the Presence of Resistance to other ASPB?
Authors: Lodise Thomas , Puzniak Laura A , Wei Rong , Tian Yun , Im Theresa M , Chen Lie Hong , Tartof Sara 
Published: January 2021

Abstract

Background
The most commonly prescribed antibiotics for PSA HAP/VAP are ASPBs: meropenem (MER), piperacillin/tazobactam (TZP),cefepime (FEP) and ceftazidime (CAZ). Similar resistance mechanisms in PSA affect these agents, and it is unclear if you can use a susceptible ASPB when the PSA is resistant to other ASPBs. This study evaluates the impact of ASPB resistance among pts with PSA HAP/VAP who initially received therapy with an ASPB to which PSA was susceptible.

Methods
A cohort study of Kaiser Permanente Southern California (KPSC) members (1/1/11-12/31/17) was performed. Inclusion criteria: (1) age ≥ 18 years; (2) HAP/VAP diagnosis; (3) monomicrobial PSA on a clinical respiratory culture (index PSA); (4) ICU at index PSA; (5) received MER, TZP, FEP or CAZ within ≤ 2 days of index PSA; (6) index PSA was susceptible to ASPB received; (7) no cystic fibrosis; (8) survived &gt; 2 days post index PSA, and (9) ≥ 6 months of KPSC membership prior to index PSA. Pts were stratified by presence of resistance to MER, TZP, and FEP on index PSA (0 vs. ≥1 resistant ASPB). Outcomes: 30-day mortality and discharge to home.

Results
560 patients were included. Mean (SD) age was 70.5 (14.2) years, 60% were male, and most had many comorbidities. Thirty-day mortality was 28%, and 32% were discharged home. Ninety-five (17%) received an active ASPB for PSA HAP/VAP that was resistance to ≥ 1 ASPB. Relative to pts with no ASPB resistance, pts with resistance ≥ 1 ASPB had higher 30-day mortality (32% vs. 27%) and were less likely to be discharged home (17% vs. 35%). In multivariate analyses, pts with resistance ≥ 1 ASPB had higher 30-day mortality (aOR=1.61 [CI: 1.01-2.56]) and were less likely to be discharged home (aHR [95%]: 0.5 [0.3-0.9]).
Crude and Adjusted Associations Between Presence of Anti-Pseudomonal β-Lactam -Resistance (Reference= no ASPB resistance) and Outcomes among Adult, ICU patients with HAP/VAP due to PSA who received a Microbiologic Active Anti-Pseudomonal β-Lactam

Conclusion
Despite receiving a microbiologic active agent within ≤ 2 days of their PSA HAP/VAP, pts with PSA that were resistant to ≥ 1 ASPB had worse outcomes relative to those that had no ASPB resistance. Further study is needed, but these findings suggest that the full ASPB susceptibility profile needs to be considered when selecting therapy for pts with PSA HAP/VAP. More studies are also needed to determine if alternative or combination therapies may be needed to maximize outcomes in PSA infection when there is resistance ≥ 1 ASPB.

Disclosures
Thomas Lodise, PharmD, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Laura A. Puzniak, PhD, Merck (Employee) Rong Wei, MA, Kaiser Permenante (Research Grant or Support) Yun Tian, MS, Merck (Research Grant or Support) Theresa M. Im, MPH, Merck (Research Grant or Support) Lie Hong Chen, DrPH, Merk (Research Grant or Support) Sara Tartof, PhD, Merck (Grant/Research Support)