Vancomycin penetration into intra-abdominal compartments: Site concentration disparities and implications for dose optimization in gram-positive infections

Objective To characterize vancomycin penetration into intra-abdominal infection sites (ascites and bile) in critically ill patients with Gram-positive complicated intra-abdominal infection (cIAI), and to explore whether incorporating site-specific therapeutic drug monitoring (TDM) is associated with better clinical outcomes compared to standard serum TDM alone. Methods This prospective, single-center observational cohort study enrolled ICU patients with Gram-positive cIAI from 2021 to 2024. All patients received vancomycin administration and underwent TDM of serum drug concentrations (serum-only group), while a subset of patients also underwent TDM of the infection site fluid (bile/ascites, dual-TDM group). Primary outcome: vancomycin TDM concentration and target attainment among the cIAI patients. Secondary outcomes: Efficacy and safety among the two groups, and vancomycin penetration in bile/ascites. Results A total of 39 patients were included in this study, with 25 in dual-TDM and 14 in serum-only TDM. Serum trough concentration (Cmin) was 12.04 (8.60-15.87) mg/L and area under the concentration-time curve over 24 hours/ minimum inhibitory concentration (AUC24h/MIC) was 448.45 (325.89-855.07). Vancomycin exposure was significantly higher in ascites than in bile (11.67 ± 3.60 vs 4.31 ± 2.11 mg/L; P < .0001). Penetration rates were 65.99% ± 26.90% in ascites and 18.50% ± 9.48% in bile (P < .0001). Compared with serum-only TDM, dual-TDM was associated with higher clinical efficacy (88.00% vs 57.14%; P = .047) and microbiological efficacy (92.00% vs 57.14%; P = .016), without increased adverse events. Conclusion Vancomycin demonstrates adequate penetration into ascitic fluid but markedly limited penetration into bile. In this exploratory cohort, dual-TDM was associated with higher target attainment and apparent clinical benefit, but allocation was non-random and the analysis was under-powered; site-specific TDM, alongside consideration of alternative anti-Gram-positive agents for biliary infections, warrants confirmation in adequately powered randomized trials. © 2026 Elsevier Ltd and International Society of Antimicrobial Chemotherapy.