Abstract
Aims Augmented renal clearance (ARC), which is commonly defined as increased renal clearance above 130 ml/min/1.73 m2, is a common phenomenon among critically ill patients. The increased elimination rate of drugs through the kidneys in patients with ARC can increase the risk of treatment failure due to the exposure to subtherapeutic serum concentrations of medications and affect the optimal management of infections, length of hospital stay, and outcomes. The main goal of this review article is to summarize the recommendations for appropriate dosing of antibiotics in patients with ARC. Methods This article is a narrative review of the articles that evaluated different dosing regimens of antibiotics in patients with ARC. The keywords “Augmented Renal Clearance,” “Critically ill patients,” “Drug dosing,” “Serum concentration,” “Beta-lactams,” “Meropenem,” “Imipenem,” “Glycopeptide,” “Vancomycin,” “Teicoplanin,” “Linezolid,” “Colistin,” “Aminoglycosides,” “Amikacin,” “Gentamycin,” “Fluoroquinolones,” “Ciprofloxacin,” and “Levofloxacin” were searched in Scopus, Medline, PubMed, and Google Scholar databases, and pediatric, nonhuman, and non-English studies were excluded. Results PK properties of antibiotics including lipophilicity or hydrophilicity, protein binding, the volume of distribution, and elimination rate that affect drug concentration should be considered along with PD parameters for drug dosing in critically ill patients with ARC. Conclusion This review recommends a dosing protocol for some antibiotics to help the appropriate dosing of antibiotics in ARC and decrease the risk of subtherapeutic exposure that may be observed while receiving conventional dosing regimens in critically ill patients with ARC.
Highlights
To the best of our knowledge, there is no published guideline for drug dosing in patients with augmented renal clearance (ARC). e main goal of this narrative review article is to summarize the recommendations for appropriate dosing of antibiotics in ARC to reduce the risk of subtherapeutic exposure that may be observed while receiving conventional dosing regimens in critically ill patients with ARC
Studies that described the impact of ARC on the dosing regimens of antibiotics, based on achieving target pharmacokinetic/pharmacodynamic (PK/PD) indices, have increased in recent years. ere are some review articles aimed to recommend dosing regimens for antibiotics in patients with ARC, but each contains only a few antibiotics, B-lactams and vancomycin [4, 8, 15, 57, 58]
Udy A.A. et al reported 82% and 72% of trough levels were less than the minimum inhibitory concentration (MIC) and 4 × MIC, respectively, in critically ill patients with ARC treated with empirical doses of B-lactams [29]
Summary
Augmented renal clearance (ARC) is a common phenomenon in critical care settings. e incidence of ARC was reported between 14 and 85% depending on the study population and the cutoff value of creatinine clearance (CrCl). e CrCl ≥130 ml/min/1.73 m2 has been considered the ARC phenomenon in most studies, different values have been suggested as well. e elimination rate of drugs, especially hydrophilic antibiotics that are mainly eliminated through the kidney, increased in ARC. Augmented renal clearance (ARC) is a common phenomenon in critical care settings. E incidence of ARC was reported between 14 and 85% depending on the study population and the cutoff value of creatinine clearance (CrCl). E CrCl ≥130 ml/min/1.73 m2 has been considered the ARC phenomenon in most studies, different values have been suggested as well. According to the effect of ARC on the optimal management of infections, length of hospital stay, and clinical outcomes, determination of the ARC phenomenon is necessary for adjusting the optimal treatment to reduce the risk of subtherapeutic exposure that may be observed while receiving conventional dosing regimens in critically ill patients with ARC. E higher rate of renal elimination of the medications in ARC impacts the dosing regimens of antibiotics to achieve target pharmacokinetic/pharmacodynamic (PK/PD) indices. We tried to prepare an almost complete article that involved most antibiotics with renal excretion
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