2026 Southeastern Residency Conference

Background/Purpose: 
Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales bacteremia is associated with increased morbidity and mortality. Although carbapenems are considered standard therapy, their use is not always feasible in clinical practice, emphasizing the need for evidence supporting effective alternative strategies. Newer β-lactam/β-lactamase inhibitor combinations, including ceftolozane/tazobactam and ceftazidime/avibactam, demonstrate activity against ESBL-producing organisms, but comparative effectiveness remains limited.  
 
The purpose of this study was to evaluate clinical outcomes of patients with ESBL bacteremia treated with meropenem compared with ceftolozane/tazobactam, or ceftazidime/avibactam.  
 
Methodology:  
This multicenter retrospective cohort study included adult patients (≥18 years) with at least one positive blood culture for ESBL-producing Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis who received ≥48 hours of definitive monotherapy with meropenem, ceftolozane/tazobactam, or ceftazidime/avibactam. Patients were identified through electronic medical records reports across AdventHealth hospital campuses. A retrospective chart review was conducted for encounter occurring between August 1, 2022, and December 31, 2025.  
 
The primary outcome was clinical efficacy, defined as a composite of: resolution of fever by day 5, improvement in leukocytosis (white blood cell count ≤10,000/µL) by day 5, no vasopressor requirement at day 5, survival at hospital discharge or 30 days from admission, and absence of recurrent primary infection due to ESBL-producing Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis at day 5. 
 
Secondary outcomes included 14-day all-cause mortality, hospital length of stay, need for transfer to a higher level of care ≥48 hours after treatment onset, escalation or change in antimicrobial therapy, and serious adverse events such as Clostridioides difficile infection and seizures. A Desirability of Outcome Ranking (DOOR) analysis was performed to evaluate overall clinical outcomes incorporating treatment response, safety events, and mortality. 
 
Results:  
A total of 68 patients met inclusion criteria and were included across three treatment groups: meropenem (MEM, n=44), ceftolozane/tazobactam (C/T, n=10), and ceftazidime/avibactam (CZA, n=14). Baseline characteristics were generally comparable between groups, with similar illness severity based on Pitt bacteremia scores. Clinical success rates did not significantly differ between treatment groups (MEM 68.2% vs C/T 70% vs CZA 78.6%; p>0.05). No statistically significant differences were observed in recurrence of infection, 14-day all-cause mortality, hospital length of stay, transfer to higher level of care, or adverse events such as seizures. However, antibiotic change occurred significantly more often in the BL/BLI groups compared with meropenem (C/T 30%, p<0.001; CZA 21.4%, p=0.002), with most changes involving transition to meropenem therapy. DOOR analysis demonstrated similar overall patient outcomes across treatment groups without statistically significant differences.   
 
Conclusions:  
In this multicenter retrospective cohort study, meropenem and novel β-lactam/β-lactamase inhibitor agents demonstrated comparable clinical efficacy and mortality outcomes for treatment of ESBL bloodstream infections. While overall outcomes were similar, meropenem showed greater therapeutic stability, reflected by the absence of antibiotic change. Interpretation is limited by the retrospective design and small sample size, highlighting the need for larger prospective studies to better define the role of these agents in ESBL bacteremia management.