Extended-interval aminoglycoside therapy for adult patients with febrile neutropenia: A systematic review

Abstract

Background: Although the efficacy and toxicity of extended-interval (once-daily) aminoglycoside regimens is well established for immunocompetent patients, there is clinical concern about using this regimen for patients with neutropenia. Objective: To summarize and evaluate the literature reporting the clinical efficacy and safety of extended-interval aminoglycosides therapy in adults with febrile neutropenia. Methods: A literature search was conducted within PubMed, Embase, and the Cochrane Database of Systematic Reviews to identify studies assessing the use of extended-interval aminoglycosides for treating febrile neutropenia in adults. Articles were categorized by quality of evidence, according to the rating scale of the US Preventive Services Task Force. Results: Ten articles were identified: 5 with level I evidence, 1 with level II-2 evidence, and 4 with level III evidence. Review of the 5 studies with level I evidence (all open-label randomized controlled trials), which compared extended-interval dosing with multiple-daily dosing strategies, revealed no evidence to suggest superiority of one regimen over the other in terms of clinical outcomes. In the study with level II-2 evidence (a prospective comparative trial), the response rate was better in the extended-interval group than in the standard-therapy group. Two of the studies with level III evidence (both prospective noncomparative trials) also had acceptable response rates to extended-interval aminoglycoside therapy, with minimal associated nephrotoxicity. In this review, no major differences in rates of nephrotoxicity or ototoxicity were seen between the 2 dosing regimens. Conclusions: The use of extended-interval dosing for aminoglycosides, in combination with other recommended antibiotic therapy, is an effective and safe management strategy for immunocompromised patients with febrile neutropenia. In this population, the clinical efficacy and safety of extended-interval dosing does not appear to differ from those of standard dosing. Whether routine or selective pharmacokinetic monitoring in this patient subpopulation leads to improvements in outcomes is yet to be determined.