title: Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review.
abstract: 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 <10 or <5 mg/L. It was not clear whether these targets were achieved. Measured peaks averaged 28 mg/L for twice-daily dosing and 40-45 mg/L for once-daily dosing; troughs averaged 5 and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in 12 and 8 studies.
  
  
  
  This systematic review found little published evidence to support an optimal dosage regimen or TDM targets for amikacin therapy. The use of alternative approaches, such as consensus opinion and a review of current practice, will be required to develop guidelines to maximize therapeutic outcomes and minimize toxicity with amikacin.
authors: British Society for Antimicrobial Chemotherapy, Birmingham, UK ajenkins@bsac.org.uk.
authors: Abi
authors: A
authors: Jenkins
authors: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK Pharmacy Department, Glasgow Royal Infirmary, Glasgow, UK.
authors: Alison H
authors: AH
authors: Thomson
authors: Clinical Microbiology and Public Health Laboratory, Addenbrooke's Hospital, Cambridge CB2 0QW, UK.
authors: Nicholas M
authors: NM
authors: Brown
authors: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK Pharmacy Department, Glasgow Royal Infirmary, Glasgow, UK.
authors: Yvonne
authors: Y
authors: Semple
authors: Pharmacy Department, Southmead Hospitals, North Bristol NHS Trust, Bristol, UK.
authors: Christine
authors: C
authors: Sluman
authors: Specialist Microbiology Services South-West, Public Health England, Southmead Hospital, Bristol, UK Antimicrobial Reference Laboratory, Infection Sciences, North Bristol NHS Trust, Bristol BS10 5NB, UK.
authors: Alasdair
authors: A
authors: MacGowan
authors: Antimicrobial Reference Laboratory, Infection Sciences, North Bristol NHS Trust, Bristol BS10 5NB, UK.
authors: Andrew M
authors: AM
authors: Lovering
authors: Cochrane Pain, Palliative and Supportive Care Group, Pain Research, Churchill Hospital Oxford, Old Road, Headington, Oxford OX3 7LE, UK.
authors: Phil J
authors: PJ
authors: Wiffen
mesh_terms: D000328:Adult; D000583:Amikacin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D065186:Interrupted Time Series Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000583:Amikacin