The aim of this research is to determine whether amikacin dosage guidelines for multi - drug resistant mycobacterial infections achieve peaks of 35 - 45 mg/L (OD) or 65 - 80 mg/L (TW) and troughs <5 mg/L

Bao, Lock

Cairney, Tamara M

Robb, Fiona

Thomson, Alison H

University of Strathclyde Institutional Repository

Cairney, Tamara M and Bao, Lock and Robb, Fiona and Thomson, Alison H (2016) Amikacin concentrations and target ranges for mycobacterial infection. In: Federation of Infection Societies/Healthcare Infection Society, 2016-11-05 - 2016-11-07, Edinburgh International Conference Centre. , This version is available at https://strathprints.strath.ac.uk/61234/Strathprints is  designed  to  allow  users  to  access  the  research  output  of  the  University  of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may  not  engage  in  further  distribution  of  the  material  for  any  profitmaking  activities  or  any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge. Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output.References1. Peloquin CA, et al. Aminoglycoside Toxicity: Daily versus thrice-weekly dosing for treatment of mycobacterial diseases. Clin Inf Dis 2004;38:1538ʹ1544. 2. Kelman AW, et al. OPT: a package of computer programs for parameter optimisation in clinical pharmacokinetics. Br J Clin Pharmacol 1982;14:247ʹ256.Summary and Conclusionsͻ Amikacin guidelines for mycobacterial infections achieve peak concentrations that are typically within or above the stated target range.ͻ Trough concentrations are excessive for patients with renal impairment (CrCl <30 mL/min).ͻ Guidelines should be modified to allow greater flexibility in peak concentrations and to provide guidance for patients with renal impairment.Aimͻ To determine whether amikacin dosage guidelines for multi-drug resistant mycobacterial infections achieve peaks of 35-45 mg/L (OD) or 65-80 mg/L (TW) and troughs <5 mg/L.Tamara M Cairney1,2, Bao Lock2, Fiona Robb1, Alison H Thomson1,21NHS Greater Glasgow and Clyde, Glasgow, 2University of Strathclyde, GlasgowIntroductionͻ Amikacin is increasingly being used in the management of multi-drug resistant mycobacterial infection.ͻ Current dosing guidelines recommend 15 mg/kg once daily (OD) or 25 mg/kg thrice weekly (TW).1ͻ Target concentrations for amikacin are end of infusion peaks of 35-45 mg/L (OD) or 65-80 mg/L (TW) and troughs <5 mg/L.1ͻ It is not clear whether the recommended amikacin dosage guidelines achieve these target concentrations.Resultsͻ Data were collected from 83 patients (Table 1), of which 33% (OD) and 35% (TW) had predicted peaks within the relevant target amikacin range (Table 2).ͻ Concentrations were more likely to be above than below the upper concentration target range (Table 2, Figure 1 and Figure 2).ͻ 34% of patients achieved peaks >50 mg/L with the OD regimen and 11% of patients achieved peaks of >100 mg/L on the TW regimen.ͻ Patients with estimated creatinine clearance <30 mL/min had troughs >5 mg/L at the end of the dosage interval.Amikacin Concentrations and Target Ranges for Mycobacterial InfectionMethodsͻ Patients >18 years old with a mycobacterial infection and at least one recorded amikacin dose and peak concentration were included in the audit.ͻ The following data were extracted from drug monitoring forms: age; weight; height; creatinine concentration; amikacin doses, concentrations and times.ͻ Individual estimates of amikacin volume of distribution (V) and clearance (CL) were determined by MAP Bayesian pharmacokinetic analysis.2ͻ Individual CL and V estimates were used to predict the following amikacin concentrations ʹ 15 mg/kg daily 1 h and 24 h after the start of a 1 h infusionʹ 25 mg/kg thrice weekly 1 h and 48 h after the start of a 1 h infusion ͻ The percentages of patients who achieve amikacin concentrations below, within and above the target peak and trough ranges were determined for each regimen.Clinical characteristics Number/Median (Range)Patients (Male/Female) 83 (49/34)Age 45 (19 ʹ 79)Weight 60 (36 ʹ 94)Estimated Creatinine Clearance (mL/min) 69 (60 ʹ 193)Estimated Amikacin Clearance (L/h) 4.0 (0.49 ʹ 10.4)Estimated Amikacin Volume of Distribution (L) 17.9 (8.6 ʹ 44.4)Figure 1 Predicted steady state peak and trough amikacin  concentrations ONCE DAILY regimen Figure 2 Predicted steady state peak and trough amikacin concentrations   THRICE WEEKLY regimenRegimen Amikacin Concentration (mg/L)Percentage of Patients15 mg/kg once dailyPeak <35 14%Peak 35 ʹ 45 33%Peak >45 53%Trough <5 94%25 mg/kg thrice weeklyPeak <65 25%Peak 65 ʹ 80 35%Peak >80 40%Trough <5 95%Table 1 Patient demographic and clinical data Table 2 Percentages of amikacin peaks and troughs within ranges 0.010.020.030.040.050.060.070.080.090.00 20 40 60 80AmikacinConcentration (mg/L)Patient NumberPeak ConcentrationTrough ConcentrationTarget Range LimitsTrough Limit0.020.040.060.080.0100.0120.00 20 40 60 80Amikacin Concentration (mg/L)Patient NumberPeak ConcentrationTrough ConcentrationTarget Range LimitsTrough Limit

Amikacin concentrations and target ranges for mycobacterial infection

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