Comparative Evaluation of Amoxicillin–Clavulanate and Ertapenem in an Exploratory Rat Model of ESBL E. coli Peritonitis

Background: Extended-spectrum β-lactamase (ESBL)–producing Escherichia coli represent an increasing therapeutic challenge. While ertapenem (ERP) is commonly used as first-line therapy, amoxicillin–clavulanic acid (AMC) achieves therapeutic concentrations in serum and ascitic fluid and may offer a narrower-spectrum alternative. This exploratory preclinical study evaluated whether AMC produces effects comparable to ERP in a rat model of ESBL E. coli peritonitis. Methods: Thirty-three male rats were allocated to four groups: untreated E. coli, AMC, ERP, and sham controls. Peritonitis was induced by intraperitoneal injection of an ESBL-producing E. coli strain. The primary outcome was peritoneal bacterial culture positivity. Secondary outcomes included plasma inflammatory cytokines (CRP, PCT, TNF-α, IL-1β, IL-6), proteomic signaling markers, and histopathological inflammation scores in the peritoneum, spleen, and lungs. Results: One death occurred in the untreated group. Both AMC and ERP were associated with lower peritoneal culture positivity compared with untreated animals, with ERP achieving statistical significance and AMC showing a similar downward trend. Inflammatory cytokines and proteomic markers demonstrated comparable reductions in both treated groups. Histopathology showed reduced inflammatory scores, with AMC exhibiting the lowest peritoneal inflammation. Lung involvement was observed in 7/10 untreated rats versus 5/10 AMC- and ERP-treated rats; these differences were not statistically significant, reflecting the limited sample size. Conclusions: AMC and ERP produced broadly comparable effects on microbiological, biochemical, and inflammatory parameters in ESBL E. coli peritonitis. These findings suggest that AMC may merit further investigation as a potential narrower-spectrum option, though definitive comparisons require larger, adequately powered studies.