Aminoglycosides: Single- or Multiple-daily Dosing? An Updated Qualitative Systematic Review of Randomized Trials on Toxicity and Efficacy

Introduction: Aminoglycosides are among the first-choice antibiotics for routine clinical use. However, dose-limiting factors such as ototoxicity and nephrotoxicity are considered as serious complications of aminoglycosides. Objective: In this systematic review, the main goal was to investigate the efficacy and incidence of nephrotoxicity and ototoxicity of once-daily dosing (ODD) and multiple daily dosing (MDD) regimens of aminoglycosides through available randomized controlled trials (RCTs). Methods: We performed a literature-based research in relevant databases, including EMBASE, MEDLINE, and SCOPUS published between 1987 and 2023 using the keywords “aminoglycosides”, “pharmacokinetics”, “ODD”, “MDD”, “once daily”, “multiple daily”, “dosing regimen”, “nephrotoxicity”, “ototoxicity”, “efficacy”, “safety”, and “toxicity”. As so told, the results of this article were limited to papers available in English. Our initial search yielded 1124 results. After a review of the titles and abstracts of the articles, 803 articles were excluded from this study because they did not address the toxicity and effectiveness of ODD versus MDD of aminoglycosides. A total number of 20 studies on gentamicin, tobramycin, netilmicin, and amikacin met the inclusion criteria for the efficacy of aminoglycosides and their role in ototoxicity and nephrotoxicity were included in this review. Studies recruited different age classes, and the age of relevant cohorts varied from only a few days to more than 70 years. Results: The most common clinical condition in the included studies was cystic fibrosis. Conclusion: In most studies, there were no significant differences between the two regimens regarding ototoxicity. In addition, the ODD regimens were safer than MDD concerning nephrotoxicity.