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EAHP Statement 4: Clinical Pharmacy Services. EAHP Statement 5: Patient Safety and Quality Assurance.
What is already known on this topic
Amikacin is receiving increased interest as an antibiotic option for multidrug-resistant organisms.
Amikacin and other aminoglycosides require therapeutic drug monitoring to minimise the risk of nephrotoxicity.
Increasing prevalence of antimicrobial resistance in key pathogens has led to changes to susceptibility breakpoints and theoretical dosing recommendations in European-wide guidelines, including a recommendation for high-dose amikacin for certain pathogens.
What this study adds
The current literature reporting data and outcomes with high-dose amikacin regimens has a high degree of bias and is confounded by poor study design and, as a result, there is insufficient evidence to provide guidance on how to manage high-dose amikacin.
Appropriate dosing weight for obese patients, adjustment for renal impairment, monitoring interval, potential toxicity and key pharmacokinetic/pharmacodynamic targets to guide treatment with high-dose amikacin regimens remain poorly defined in the current literature.
How this study might affect research, practice or policy
Further evidence and/or consensus guidelines based on expert judgement are required to ensure patients can receive optimal therapy when amikacin is the treatment of choice.
Introduction
Aminoglycosides are widely used antibiotics for the treatment of Gram-negative infections, and the increasing prevalence of multidrug-resistant Gram-negative organisms has renewed interest in their use.1 Numerous resistance mechanisms to aminoglycosides exist, including the increasingly prevalent aminoglycoside-modifying enzymes and also 16S rRNA methyltransferases.2 Amikacin is less susceptible to many of the common aminoglycoside-modifying enzymes in Gram-negative pathogens,3 therefore it provides a valuable treatment option in patients or populations with gentamicin resistance.
Amikacin is licensed, and traditionally used, at a dose of 15 mg/kg once daily or 7.5 mg/kg twice daily. Additionally, the manufacturer cautions against exceeding a single dose of 1.5 g/day and a total course of more than 15 g.4 There is renewed interest in high-dose amikacin regimens, based on an increasing understanding of the pharmacokinetic/pharmacodynamic (PK/PD) factors associated with target attainment and maximal killing, and limitation of mutant selection due to suboptimal dosing. Thus, understanding how to optimise dosing of amikacin to balance the treatment efficacy with known treatment toxicities (eg, nephrotoxicity and ototoxicity) is increasingly important.
Recent European Committee on Antimicrobial Susceptibility Testing (EUCAST) changes to antimicrobial susceptibility breakpoints