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

TL;DR

This review discusses how to properly dose new antibiotic combinations in sepsis patients with kidney failure undergoing dialysis.

Contribution

The paper provides practical dosing guidance for β-lactam/β-lactamase inhibitors during renal replacement therapy.

Findings

Standard dosing often leads to subtherapeutic antibiotic levels in critically ill patients on dialysis.

Drug exposure is influenced by dialysis modality, membrane properties, and patient-specific factors.

Full-dose initiation followed by adjustment is recommended, with therapeutic drug monitoring when available.

Abstract

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.

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