PSHP 2026 Residency Conference

Dual beta-lactam (DBL) regimens are leveraged for a variety of infections. Concerns regarding additive toxicity are prevalent despite limited evidence. This study aimed to describe the safety and tolerability of contemporary DBL regimens.


This was a retrospective single-arm cohort study including adult inpatients who received at least 72 hours of pre-specified DBL regimens from September 2021 to August 2025. Patients were excluded if any portion of a DBL course was given at an outside hospital. The primary outcome was the incidence of adverse drug events (ADEs) associated with DBL discontinuation. DBL discontinuation was defined as cessation of one or both beta-lactams due to a documented ADE. Secondary outcomes included time-to-ADE metrics and incidence of pre-specified ADE types (renal, neurologic, hepatobiliary, hematologic, hypersensitivity, or gastrointestinal). Causality was assessed using the WHO-UMC system with secondary adjudication by a co-investigator. Baseline characteristics and outcomes were analyzed using descriptive statistics. The Wilson Score method was used to calculate a 95% confidence interval (CI) for ADE incidence. 


A total of 175 patients were included. The most common DBL regimens were ceftriaxone plus ampicillin (52.0%) and cefepime plus ampicillin (21.7%). The most common DBL indications were E. faecalis synergy and empiric coverage of meningitis. A total of 124 patients (70.8%) had DBL therapy discontinued during admission. Only six discontinuations were associated with a documented ADE (3.4%; 95% CI, 1.6-7.3). Of these, only three were assigned a causality of possible or higher (1.7%; 95% CI, 0.6-4.9). These were leukopenia (n=2) and gastrointestinal intolerance (n=1), which resolved with DBL discontinuation. The median time to any ADE associated with DBL discontinuation was 6.5 days (IQR, 5.3-7.9). 


Treatment-limiting ADEs associated with contemporary DBL regimens were rare and reversible with discontinuation. These findings reinforce conclusions reported in prior literature. These results also suggest that clinicians’ perceived risk of DBL-related ADEs is likely to far exceed the actual risks associated with these regimens. Our findings support the use of DBL when clinically appropriate and in alignment with antimicrobial stewardship.