Does dose reduction of renally cleared antibiotics in patients with impaired renal function lead to adequate drug exposure? A systematic review

Background: There is inconsistency between many guidelines in the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function. Objectives: This systematic review summarizes the available evidence on the adequacy of the recommended dose reduction in terms of achieving sufficient antibiotic drug exposure or pharmacokinetic/pharmacodynamic target attainment after treatment with these reduced doses. Data sources: We systematically searched Ovid Medline and Embase from inception (respectively 1946 and 1947) through July 2019. Study eligibility criteria: All studies reporting antibiotic drug exposure and/or pharmacokinetic/pharmacodynamic (PK/PD) target attainment after dose reduction of antibiotics in patients with impaired renal function. Participants: Adult patients with or without infections. Interventions: Administration of reduced doses of antibiotics (orally, intravenously or intramuscularly). Methods: The reduced dose was considered adequate when the most relevant parameters of drug exposure or PK/PD target attainment in patients with impaired renal function were within a range of 80% to 125% of that patients with adequate renal function receiving a regular dose (reference) or when PK/PD target attainment was attained in at least 90% of the patients with impaired renal function, regardless of the lack of a reference group. Results: Twenty-seven of the 4202 identified studies were included. The quality of 15 of 27 studies was fair, and most studies were of β-lactams (12/27). Best evidence was available for meropenem: four studies were included, of which two studies were of good quality. Drug exposure for meropenem is 158% to 286% higher in patients with impaired renal function receiving reduced doses compared to patients with adequate renal function receiving regular doses. For all other antibiotics, a maximum of one good-quality study could be identified. Conclusions: No good-quality evidence on the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function is present, with the exception of meropenem.