The comparison of adverse events in combination with double beta-lactam antimicrobials: Ampicillin plus Ceftriaxone and Ampicillin/Cloxacillin with bloodstream infections.

Background: We frequently administered double beta-lactam, but the incidence rate of adverse events remains unclear. In Japan, only ampicillin/cloxacillin (ABPC/MCIPC) is available as anti-staphylococcal penicillin for Staphylococcus aureus bacteremia. Our goal was to investigates the adverse events of double beta-lactam. Methods: Adult patients (≥18 years) with bacteremia treated with ABPC, ABPC+CTRX, or ABPC/MCIPC were retrospectively analyzed. The primary outcome of this study was the incidence of adverse events. Chi-square and T-tests were used for bivariate analysis. To analyze acute kidney injury (AKI) events, Kaplan-Meier analysis, the log-rank test, and Cox proportional hazards models were performed. Propensity score (PS) matching was conducted to adjust for confounding factors. Results: We included 277 ABPC, 57 ABPC+CTRX, and 43 ABPC/MCIPC patients. There were significant differences in age (71.1[standard deviation: SD 16.5], 64.0[16.9], 56.6[17.5]), number of male patients (62.5%, 47.4%, 72.1%), proportion of patients with qSOFA score ≥2 (23.1%, 64.4%, 41.9%), incidence of chronic kidney disease (39.0%, 35.1%, 18.6%), treatment duration[SD] (14.0 [12.1], 9.3 [8.8], 29.0 [19.2]), mechanical ventilation use (5.4%, 24.6%, 20.9%), vasopressor use (10.5%, 31.6%, 23.3%), and proportion of patients with AKI KDIGO grade ≥ 2 (9.0%, 12.3%, 30.2%). Kaplan–Meier analysis showed a significant difference between ABPC and ABPC/MCIPC with hazard ratio of 1.83(95% confidence interval, 1.22–2.74, p=0.003) in AKI. In the PS-matched cohort, the incidence of AKI in AMPC/MCIPC was a significantly higher compared to the ABPC. Conclusions: ABPC+CTRX may be safe under certain conditions, whereas ABPC/MCIPC presents a higher risk of AKI and may not be suitable.