Adverse Events Comparison of Double Beta-Lactam Combinations for Bloodstream Infections: Ampicillin plus Ceftriaxone and Ampicillin/Cloxacillin

Abstract

In Japan, only ampicillin/cloxacillin (ABPC/MCIPC) is available as an anti-staphylococcal penicillin-based treatment for Staphylococcus aureus bacteremia. However, the incidence of adverse events associated with double beta-lactam administration remains unknown. Therefore, we investigated the adverse events of double beta-lactam administration in patients with bacteremia. Adult patients (≥18 years) with bacteremia treated with ABPC, ABPC + ceftriaxone (CTRX), or ABPC/MCIPC were retrospectively analyzed. The primary outcome of this study was the incidence of adverse events such as acute kidney injury, liver dysfunction, and myelosuppression. Chi-square tests and t-tests were used for bivariate analysis. Propensity score (PS) matching was conducted to adjust for confounding factors. We included 277 ABPC-, 57 ABPC + CTRX-, and 43 ABPC/MCIPC-treated patients. Significant differences were noted in age, number of male patients, proportion of patients with qSOFA score ≥2, incidence of chronic kidney disease, treatment duration, mechanical ventilation use, vasopressor use, and proportion of patients with acute kidney injury (AKI) KDIGO grade ≥2. Further, a significant difference was observed between ABPC and ABPC/MCIPC, with a hazard ratio of 1.83 in AKI. In the PS-matched cohort, AKI incidence associated with ABPC/MCIPC was significantly higher than that associated with ABPC. ABPC + CTRX may be safe, whereas ABPC/MCIPC presents a higher risk of AKI and may not be suitable.

Keywords

• acute kidney injury
• ampicillin/cloxacillin
• beta-lactam
• double beta-lactam