Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review

• Published in: Journal of antimicrobial chemotherapy 2016-10, Vol.71 (10), p.2754-2759
• Main Authors: Jenkins, Abi, Thomson, Alison H, Brown, Nicholas M, Semple, Yvonne, Sluman, Christine, MacGowan, Alasdair, Lovering, Andrew M, Wiffen, Phil J
• Format: Article
• Language: English
• Subjects: Adult; Amikacin - administration & dosage; Amikacin - adverse effects; Amikacin - blood; Amikacin - therapeutic use; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - therapeutic use; Dose-Response Relationship, Drug; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Humans; Interrupted Time Series Analysis; Treatment Outcome
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkw250

The objectives of this study were to identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity. A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles reporting randomized controlled trials, controlled clinical trials, interrupted time series trials, and controlled before and after studies involving amikacin therapeutic drug monitoring (TDM) and dose adjustment were considered for inclusion. Seventeen studies for inclusion were identified, comprising 1677 participants. Amikacin doses ranged from 11 to 15 mg/kg/day with 13 studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only 11 papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 to 40 mg/L and target troughs were typically