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

Abi Jenkins, Alison H. Thomson, Nicholas M. Brown, Yvonne Semple, Christine Sluman, Alasdair MacGowan, Andrew M. Lovering, Phil J. Wiffen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objectives To identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity. Methods A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles of randomised controlled trials, controlled clinical trials, interrupted time series trials and controlled before and after studies involving amikacin TDM and dose adjustment were considered for inclusion. Results Seventeen included studies were identified, comprising 1677 participants. Amikacin doses ranged from 11-15 mg/kg/day with thirteen studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only eleven papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 – 40 mg/L and target troughs were typically <10 mg/L 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 mg/L and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in twelve and eight studies. Conclusions 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 maximise therapeutic outcomes and minimise toxicity with amikacin.
LanguageEnglish
Pages2754-2759
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume71
Issue number10
Early online date11 Jul 2016
DOIs
Publication statusPublished - 1 Oct 2016

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Amikacin
Drug Monitoring
Pharmaceutical Preparations
Controlled Clinical Trials
Aminoglycosides
Randomized Controlled Trials
Guidelines
Therapeutics

Keywords

  • amikacin
  • therapeutic drug monitoring
  • aminoglycosides

Cite this

Jenkins, Abi ; Thomson, Alison H. ; Brown, Nicholas M. ; Semple, Yvonne ; Sluman, Christine ; MacGowan, Alasdair ; Lovering, Andrew M. ; Wiffen, Phil J. / Amikacin use and therapeutic drug monitoring in adults : do dose regimens and drug exposures affect either outcome or adverse events? A systematic review. In: Journal of Antimicrobial Chemotherapy. 2016 ; Vol. 71, No. 10. pp. 2754-2759.
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abstract = "Objectives To identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity. Methods A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles of randomised controlled trials, controlled clinical trials, interrupted time series trials and controlled before and after studies involving amikacin TDM and dose adjustment were considered for inclusion. Results Seventeen included studies were identified, comprising 1677 participants. Amikacin doses ranged from 11-15 mg/kg/day with thirteen studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only eleven papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 – 40 mg/L and target troughs were typically <10 mg/L 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 mg/L and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in twelve and eight studies. Conclusions 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 maximise therapeutic outcomes and minimise toxicity with amikacin.",
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Amikacin use and therapeutic drug monitoring in adults : do dose regimens and drug exposures affect either outcome or adverse events? A systematic review. / Jenkins, Abi; Thomson, Alison H.; Brown, Nicholas M.; Semple, Yvonne; Sluman, Christine ; MacGowan, Alasdair; Lovering, Andrew M.; Wiffen, Phil J.

In: Journal of Antimicrobial Chemotherapy, Vol. 71, No. 10, 01.10.2016, p. 2754-2759.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Amikacin use and therapeutic drug monitoring in adults

T2 - Journal of Antimicrobial Chemotherapy

AU - Jenkins, Abi

AU - Thomson, Alison H.

AU - Brown, Nicholas M.

AU - Semple, Yvonne

AU - Sluman, Christine

AU - MacGowan, Alasdair

AU - Lovering, Andrew M.

AU - Wiffen, Phil J.

N1 - This is a pre-copyedited, author-produced PDF of an article accepted for publication in Journal of Antimicrobial Chemotherapy following peer review. The version of record Jenkins, A., Thomson, A. H., Brown, N. M., Semple, Y., Sluman, C., MacGowan, A., ... Wiffen, P. J. (2016). Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review. Journal of Antimicrobial Chemotherapy, 71(10), 2754-2759. DOI: 10.1093/jac/dkw250

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Objectives To identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity. Methods A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles of randomised controlled trials, controlled clinical trials, interrupted time series trials and controlled before and after studies involving amikacin TDM and dose adjustment were considered for inclusion. Results Seventeen included studies were identified, comprising 1677 participants. Amikacin doses ranged from 11-15 mg/kg/day with thirteen studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only eleven papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 – 40 mg/L and target troughs were typically <10 mg/L 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 mg/L and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in twelve and eight studies. Conclusions 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 maximise therapeutic outcomes and minimise toxicity with amikacin.

AB - Objectives To identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity. Methods A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles of randomised controlled trials, controlled clinical trials, interrupted time series trials and controlled before and after studies involving amikacin TDM and dose adjustment were considered for inclusion. Results Seventeen included studies were identified, comprising 1677 participants. Amikacin doses ranged from 11-15 mg/kg/day with thirteen studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only eleven papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 – 40 mg/L and target troughs were typically <10 mg/L 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 mg/L and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in twelve and eight studies. Conclusions 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 maximise therapeutic outcomes and minimise toxicity with amikacin.

KW - amikacin

KW - therapeutic drug monitoring

KW - aminoglycosides

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