Pharmacokinetic, Pharmacodynamic, and Clinical Outcomes of Vancomycin and β-Lactam Antibiotics in Adults With Augmented Renal Clearance: A Systematic Review.

Augmented renal clearance (ARC) is frequently seen in the critically ill population and may lead to faster clearance of antibiotics with renally dependent clearance. For β-lactam antibiotics and vancomycin, this may compromise drug exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment, which is a clinically relevant risk for sub-therapeutic drug exposure and treatment failure. The aim of this study was to systematically review pharmacokinetic, pharmacodynamic, microbiological, and clinical outcomes of vancomycin and β-lactam antibiotics in adults with ARC. This systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD420261300771). Studies in which adults with ARC were treated with either vancomycin or β-lactams and had data on at least one of the pharmacokinetics, pharmacodynamics, microbiology, and/or clinical endpoints were identified in PubMed, Scopus, and Cochrane Library databases. Data synthesis is presented narratively following Synthesis Without Meta-analysis (SWiM) guidelines. There were 13 studies, all conducted mostly in intensive care units. Overall, in the included studies, the most frequent pharmacokinetic pattern for the studied antibiotics was reduced clearance and lower systemic exposure of antibiotics in patients with ARC. For vancomycin, in a retrospective cohort study, more than 60% of patients with ARC had their trough levels below 10 µg/mL. In another small randomized vancomycin trial, with once-every-eight-hours dosing, area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) above 400 mg·h/L at MIC of 1 mg/L was reached in 82.14% of participants compared to 46.42% with once-every-twelve-hours dosing. In the case of β-lactams, improved PK/PD target attainment with prolonged and continuous infusion was seen in some studies. However, clinical and microbiological results were scarce. In general, ARC was linked with enhanced antibiotic clearance, decreased exposure, and inadequate PK/PD target attainment on standard dosing regimens. Optimization of dose regimens could help in improving target attainment; however, present evidence is not enough to show that there is an improvement in clinically important outcomes.