β-Lactam/β-Lactamase Inhibitor Combinations in Sepsis-Associated Acute Kidney Injury and Renal Replacement Therapy

Sepsis-associated acute kidney injury (SA-AKI) often requires renal replacement therapy (RRT), which markedly alters antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations broaden options against multidrug-resistant Gram-negative bacteria, but dosing during RRT remains uncertain. This review summarizes PK/PD features, extracorporeal clearance, and practical dosing considerations about ceftolozane–tazobactam, ceftazidime–avibactam, aztreonam–avibactam, cefiderocol, meropenem–vaborbactam, imipenem–relebactam, and newer agents including sulbactam–durlobactam, cefepime–enmetazobactam, and cefepime–taniborbactam. Pharmacokinetic data, RRT impact, PK/PD targets, pediatric aspects, and clinical outcomes were extracted from experimental models, case reports, and clinical studies. Drug exposure varies with RRT modality, effluent flow, membrane properties, and patient-specific factors such as augmented renal clearance, hypoalbuminemia, and fluid overload. Standard renal-adjusted dosing often yields subtherapeutic concentrations in critically ill patients. Pediatric data remain scarce and largely limited to case reports. Optimal BL/BLI use in septic patients with SA-AKI on RRT requires individualized dosing that accounts for PK/PD variability and dialysis settings. Full-dose initiation during the first 24–48 h, followed by careful adjustment, appears prudent. Therapeutic drug monitoring should be used when available, and institution-specific protocols should be integrated into stewardship programs to improve efficacy and minimize resistance.