2775. Clinical Outcomes and Treatment-Emergent Resistance of Piperacillin-tazobactam, Cefepime, Carbapenems and Fluoroquinolones for the Treatment of Bloodstream Infections due to AmpC β-Lactamase-Producing Enterobacterales
Authors: Jawanda Jasanjeet , O’Donnell Matthew A , Shah Sunish , Clarke Lloyd , Shields Ryan K 
Published: November 2023

Abstract

Background
Cefepime (FEP) and carbapenems (CB) are preferred over piperacillin-tazobactam (TZP) for treatment (tx) of Enterobacterales with significant AmpC production due to concerns for inducible resistance. We aimed to determine if dose-optimized TZP is as effective for bloodstream infections (BSI), and to establish rates of tx-emergent resistance in an era of β-lactam (BL) dose optimization.

Methods
Patients with BSI due to E. cloacae, K. aerogenes and C. freundii from 2017 to 2022 at two hospitals were included. We excluded patients surviving &lt; 48 hours or if polymicrobial BSI due to a Gram-negative organism resistant to BLs. Primary outcome was 30-day success, defined as survival, clinical improvement, completion of definitive tx and absence of recurrent infection. Development of resistance was assessed over 90 days.

Results
429 patients were identified; 362 met inclusion criteria. The median age was 65 years, 61% were male and median Pitt Bacteremia score was 2 (Table 1). Median (IQR) time to in-vitro active tx was 7.6 (1.4-20.7) hours. 48%, 30%, and 11% of patients received TZP, FEP, and CB as empiric tx, respectively. By comparison, 15%, 47%, and 22% received TZP, FEP, and CB as definitive tx, respectively (n=344). Patients tx’d with definitive CB were more likely to receive inactive empiric tx (p=0.0004) and have complicated BSI (p=0.015). Dose optimization was more common for TZP than FEP or CB (p=0.02). Early clinical failure was more common for CB than other agents, but similar for TZP and FEP (Table 2). 30-day clinical success rates ranged 58-85%, were lower for patients tx’d with CB (58%; p=0.0006), and comparable for TZP and FEP (p=0.25). By empiric tx, there were no differences in early clinical failures, microbiologic relapse, 30-day success, or all-cause mortality between patients tx’d with TZP or FEP (Table 3). Overall, 226, 279, and 117 patients received TZP, FEP, and CB as empiric or definitive tx. Corresponding rates of resistance development within 90 days were 2%, 1%, and 3%, respectively.
Results Table 1. Patient demographics, severity of illness, infection and treatment characteristics based on definitive therapy
Results Table 2
Results Table 3

Conclusion
Definitive tx with dose-optimized TZP did not lead to worse clinical or microbiologic outcomes compared to FEP, CB and FQ. There were no cases of tx-emergent resistance among patients who received TZP as definitive tx, and overall rates of resistance development were low.

Disclosures
Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support