Background: Amikacin remains a key agent in the treatment of severe and complicated infections due to its bactericidal activity and low risk of Clostridioides difficile infection. It retains activity against most aerobic Gram-negative bacteria, including multidrug-resistant Enterobacterales and Pseudomonas. However, its use is limited by nephrotoxicity and ototoxicity. Methods: This narrative review evaluates clinical indications, pharmacokinetic and pharmacodynamic properties, dosing strategies, therapeutic drug monitoring (TDM), and safety profile of amikacin in adult patients based on 56 selected publications. A total of 24 articles were identified through database searches (PubMed and Embase), complemented by 32 additional sources to provide clinical and pharmacological context. Results: Available evidence demonstrates considerable uncertainty regarding the comparative effectiveness of different monitoring strategies. Lower trough concentrations are generally associated with reduced nephrotoxicity; however, an optimal safety threshold has not been clearly established. Guideline-recommended targets vary substantially and are supported by low-quality evidence. Amikacin pharmacokinetics, tissue penetration and toxicity are influenced by patient-specific factors, including critical illness, renal function variability, and concomitant nephrotoxic therapy, particularly vancomycin. Ototoxicity remains an additional clinically relevant concern. Conclusions: Current evidence suggests that uniform dosing and monitoring paradigms are insufficient. Patient-tailored strategies integrating TDM and mitigation of modifiable risk factors are required. Prospective studies comparing monitoring regimens are needed to optimize the safe clinical use of amikacin and inform future guideline development.
Orzechowski et al. (Sun,) studied this question.