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

Abstract

BackgroundThere is inconsistency between many guidelines in the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function. ObjectivesThis 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 sourcesWe systematically searched Ovid Medline and Embase from inception (respectively 1946 and 1947) through July 2019. Study eligibility criteriaAll studies reporting antibiotic drug exposure and/or pharmacokinetic/pharmacodynamic (PK/PD) target attainment after dose reduction of antibiotics in patients with impaired renal function. ParticipantsAdult patients with or without infections. InterventionsAdministration of reduced doses of antibiotics (orally, intravenously or intramuscularly). MethodsThe 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. ResultsTwenty-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. ConclusionsNo 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.