Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis: A Critical Review

Abstract

Purpose: Antibiotics are frequently used in patients receiving intermittent or continuous renal replacement therapy (RRT). Continuous renal replacement may alter the pharmacokinetics (PK) and the ability to achieve PK/pharmacodynamic (PD) targets. Therapeutic drug monitoring (TDM) could help evaluate drug exposure and guide antibiotic dosage adjustment. The present review describes recent TDM data on antibiotic exposure and PK/PD target attainment (TA) in patients receiving intermittent or continuous RRT, proposing practical guidelines for performing TDM.Methods: Studies on antibiotic TDM performed in patients receiving intermittent or continuous RRT published between 2000 and 2020 were searched and assessed. The authors focused on studies that reported data on PK/PD TA. TDM recommendations were based on clinically relevant PK/PD relationships and previously published guidelines.Results: In total, 2383 reports were retrieved. After excluding nonrelevant publications, 139 articles were selected. Overall, 107 studies reported PK/PD TA for 24 agents. Data were available for various intermittent and continuous RRT techniques. The study design, TDM practice, and definition of PK/PD targets were inconsistent across studies. Drug exposure and TA rates were highly variable. TDM seems to be necessary to control drug exposure in patients receiving intermittent and continuous RRT techniques, especially for antibiotics with narrow therapeutic margins and in critically ill patients. Practical recommendations can provide insights on relevant PK/PD targets, sampling, and timing of TDM for various antibiotic classes.Conclusions: Highly variable antibiotic exposure and TA have been reported in patients receiving intermittent or continuous RRT. TDM for aminoglycosides, beta-lactams, glycopeptides, linezolid, and colistin is recommended in patients receiving RRT and suggested for daptomycin, fluoroquinolones, and tigecycline in critically ill patients on RRT.

Population Pharmacokinetics of Isavuconazole in Critical Care Patients with COVID-19-Associated Pulmonary Aspergillosis and Monte Carlo Simulations of High Off-Label Doses

“…Some findings suggest that TDM for isavuconazole should not be considered as mandatory. However, in unstudied clinical situations and for special populations (obesity, RRT, ECMO), it should be an option to consider [ 40 , 41 , 42 ].…”

The Current Status and Future Perspectives of Beta-Lactam Therapeutic Drug Monitoring in Critically Ill Patients

“…Renal failure leads to a risk of toxicity by overdosing, proving the interest of anticipating increasing serum concentrations [ 47 ]. Although there is extremely high variability of BL exposure in patients with renal failure or those undergoing RRT supports TDM and dose individualization, few studies have investigated whether TDM and subsequent dose adjustment could reduce such variability and improve BL exposure [ 79 ]. To date, no randomized study assessing TDM interventions in patients undergoing RRT has been conducted, and the optimal dose adjustment approach (empirical dosing, nomograms or dosing software) remains to be determined.…”

Antimicrobial Exposure in Critically Ill Patients with Sepsis-Associated Multi-Organ Dysfunction Requiring Extracorporeal Organ Support: A Narrative Review

“…Accordingly, recently published guidelines recommended the TDM use for dose titration of ß-lactams, aminoglycosides, linezolid, teicoplanin, vancomycin and voriconazole [ 17 ]. In critically ill patients who receive RRT and ECMO [ 95 , 96 , 97 ], TDM has been largely used for adjusting the dose of ß-lactams, aminoglycosides, linezolid, teicoplanin, glycopeptides and colistin [ 17 ]. Furthermore, some evidence has been reported for daptomycin, fluoroquinolones and Tigecycline [ 17 ], although it warrants further investigation.…”