Current status of therapeutic drug monitoring in Australia and New Zealand: a need for improved assay evaluation, best practice guidelines, and professional development.
ABSTRACT The measurement of drug concentrations, for clinical purposes, occurs in many diagnostic laboratories throughout Australia and New Zealand. However, the provision of a comprehensive therapeutic drug monitoring (TDM) service requires the additional elements of pre- and postanalytical advice to ensure that concentrations reported are meaningful, interpretable, and clinically applicable to the individual patient. The aim of this project was to assess the status of TDM services in Australia and New Zealand. A range of professions involved in key aspects of TDM was surveyed by questionnaire in late 2007. Information gathered included: the list of drugs assayed; analytical methods used; interpretation services offered; interpretative methods used; and further monitoring advice provided. Fifty-seven responses were received, of which 42% were from hospitals (public and/or private); 11% a hospital (public and/or private) and pathology provider; and 47% a pathology provider only (public and/or private). Results showed that TDM is applied to a large number of different drugs. Poorly performing assay methods were used in some cases, even when published guidelines recommended alternative practices. Although there was a wide array of assays available, the evidence suggested a need for better selection of assay methods. In addition, only limited advice and/or interpretation of results was offered. Of concern, less than 50% of those providing advice on aminoglycoside dosing in adults used pharmacokinetic tools with six of 37 (16.2%) respondents using Bayesian pharmacokinetic tools, the method recommended in the Australian Therapeutic Guidelines: Antibiotic. In conclusion, the survey highlighted deficiencies in the provision of TDM services, in particular assay method selection and both quality and quantity of postanalytical advice. A range of recommendations, some of which may have international implications, are discussed. There is a need to include measures of impact on clinical decision-making when assessing assay methodologies. Best practice guidelines and professional standards of practice in TDM are needed, supported by an active program of professional development to ensure the benefits of TDM are realized. This will require significant partnerships between the various professions involved.
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ABSTRACT: There is strong evidence in literature supporting the benefit of monitoring plasma concentrations of β-lactam antibiotics in the critically ill to ensure appropriateness of dosing. The objective of this work was to develop a method for the simultaneous determination of total concentrations piperacillin, benzylpenicillin, flucloxacillin, meropenem, ertapenem, cephazolin and ceftazidime in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 0.1% formic acid and subsequent dilution of supernatant with 0.1% formic acid in water. Chromatographic separation was achieved on a reversed phase column (C18, 2.6μm, 2.1×50mm) via gradient elution using water and acetonitrile, each containing 0.1% formic acid, as mobile phase. Tandem mass spectrometry (MSMS) analysis was performed, after electrospray ionization in the positive mode, with multiple reaction monitoring (MRM). The method is accurate with the inter-day and intra-day accuracies of quality control samples (QCs) ranging from 95 to 107% and 95 to 108%, respectively. It is also precise with intra-day and inter-day coefficient of variations ranging from 4 to 12% and 5 to 14%, respectively. The lower limit of quantification was 0.1μg/mL for each antibiotic except flucloxacillin (0.25μg/mL). Recovery was greater than 96% for all analytes except for ertapenem (78%). Coefficients of variation for the matrix effect were less than 10% over the six batches of plasma. Analytes were stable over three freeze-thaw cycles, and for reasonable hours on the bench top as well as post-preparation. This novel liquid chromatography tandem mass spectrometry method proved accurate, precise and applicable for therapeutic drug monitoring and pharmacokinetic studies of the selected β-lactam antibiotics.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 04/2014; 960C:134-144. DOI:10.1016/j.jchromb.2014.04.029 · 2.69 Impact Factor
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ABSTRACT: To evaluate prospectively the appropriateness of indications, sampling time and outcome of TDM requests at a teaching university hospital in Oman.MethodsA prospective cross-sectional study was conducted over four months period; October 2013 to January 2014 at Sultan Qaboos University Hospital (SQUH), an 855 bed university teaching hospital. Appropriateness criteria for indications and sampling time were defined a priori. The evaluated drug’s requests were carbamazepine, phenytoin, phenobarbital, valporic acid, digoxin, gentamicin, amikacin, vancomycin, tobramycin, theophylline, lithium, and cyclosporine.ResultsOf 733 evaluated TDM requisitions, the majority were for antibiotics (75.0%) followed by antiepileptics (10.5%) and cyclosporine (8.9%). Most of the requests had appropriate indication (78.2%), however, only 28.5% had appropriate sampling time. Results were applied by dosage adjustments in 65.75% of requests and some of inappropriately sampled requests (15.3%) were used as basis for modifying dosage regimen. Of all reported plasma concentrations 42.3%, 41.2%, and 16.5% were within, below and above the reference range, respectively.ConclusionTDM service is much less than optimal in SQUH. A lot of efforts need to be carried out to improve TDM use in the developing countries as adjusting the doses on results that are based on wrong sampling time might expose patients to toxicity or therapeutic failure.Saudi Pharmaceutical Journal 11/2014; DOI:10.1016/j.jsps.2014.11.005 · 1.00 Impact Factor
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ABSTRACT: This study was aimed at increasing the clinical usefulness of Clinical Pharmacological Advice (CPA) for personalized drug dosing based on therapeutic drug monitoring (TDM).Educational and organizational interventions focused on improving the knowledge of clinical pharmacology among hospital healthcare workers and reducing the incidence of errors throughout the process were planned. After a Pre-interventional period of risk assessment, different list forms of the types of error occurring in the various phases of the process (Phase 1, request for CPA and blood sampling for TDM; Phase 2, sample delivery to and check in at the CPU; Phase 3, TDM execution and CPA production) were created. In the Interventional period, the errors were collected daily and educational programmes were carried out. The pre-intervention error rate was 19.5%, and resulted significantly higher for the requests coming from the medical wards compared to those from the surgical wards or the ICUs (26.0% versus 10.5% versus 13.7%, p<0.001). The educational programme trained 303 nurses and 145 physicians. Afterwards, the error percentage progressively dropped (15.5% in the 2nd trimester; 12.3% in the 3rd one; 10.5% in the 4th one). The adopted strategy resulted in significant improvements which may be useful both to improve quality of patient care and to reduce waste in healthcare costs.This article is protected by copyright. All rights reserved.Basic & Clinical Pharmacology & Toxicology 04/2014; DOI:10.1111/bcpt.12249 · 2.29 Impact Factor