Clinical standards for the dosing and management of TB drugs

BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.CONTEXTE : Une posologie optimale est importante afin de garantir une réponse adéquate au traitement, de prévenir le développement de résistances aux médicaments et de réduire la toxicité liée aux médicaments. L’objectif de ces normes cliniques est de donner des indications de « bonne pratique » en matière de posologie et de gestion des agents antituberculeux. MÉTHODES : Un panel de 57 experts internationaux spécialisés en microbiologie, pharmacologie et soins antituberculeux a été identifié ; 51 ont participé à un processus Delphi. Une échelle de Likert à 5 points a été utilisée pour noter les premières ébauches des normes. Le document final est fondé sur un large consensus puisqu’il a été approuvé par tous les participants. RÉSULTATS : Six normes cliniques ont été définies : Norme 1, définir la dose initiale la mieux adaptée au traitement de la TB ; Norme 2, identifier les patients potentiellement à risque d’exposition sous-optimale aux médicaments ; Norme 3, identifier les patients à risque de développer une toxicité liée aux médicaments et déterminer comment diminuer au mieux ce risque ; Norme 4, identifier les patients pouvant bénéficier d’un suivi thérapeutique pharmacologique (TDM) ; Norme 5, définir les informations et conseils à fournir aux patients placés sous traitement antituberculeux et Norme 6, enseigner les fondamentaux aux professionnels de santé. Les priorités de recherche ont également été définies, sur la base d’un consensus. CONCLUSION : Il s’agit des premières normes cliniques, fondées sur un consensus, en matière de posologie et de gestion des antituberculeux. Elles ont pour objectif d’orienter les cliniciens et les responsables de programme en matière de planification et de mise en place de mesures locales adéquates pour un traitement optimal centré sur le patient, afin d’améliorer la prise en charge

Dried blood spot analysis:facing new challenges

Over the last decade, DBS analysis has gained popularity for TDM because it’s a patient friendly sampling proce- dure [1-4]. Additional advantages are prolonged sample stability, lower risk of infections and transportation at ambient temperature [1-3,5]. These advantages may fa- cilitate implementation of TDM in different clinical set- tings including resource limited areas. Patients will bene- fit from DBS analysis but the analytical development and validation of DBS methods is more complex compared to plasma or serum analysis. Additional validation parameters, like the effect of the hematocrit (HT) and blood spot volume need to be eval- uated. Drug substances may also interact with the blood matrix or with the DBS card, resulting in matrix related recovery effects. Unfortunately, official guidelines for val- idation of DBS are not available yet. However, in recent literature, several interesting issues related to analytical DBS research have been discussed [1,6-12]. Ongoing re- search and improved understanding of the factors that influence DBS analysis results will ultimately result in well-founded guidelines for DBS analytical method val- idation. This would be very helpful for daily practice but would also benefit patient safety because uniformity in method validation prevents potential pitfalls during val- idation or method development and increase credibility of assay results. Our aim is to discuss some relevant topics related to DBS development prior to development of future guidelines on DBS development and validation

Role of therapeutic drug monitoring in pulmonary infections : use and potential for expanded use of dried blood spot samples

Respiratory tract infections are among the most common infections in men. We reviewed literature to document their pharmacological treatments, and the extent to which therapeutic drug monitoring (TDM) is needed during treatment. We subsequently examined potential use of dried blood spots as sample procedure for TDM. TDM was found to be an important component of clinical care for many (but not all) pulmonary infections. For gentamicin, linezolid, voriconazole and posaconazole dried blood spot methods and their use in TDM were already evident in literature. For glycopeptides, beta-lactam antibiotics and fluoroquinolones it was determined that development of a dried blood spot (DBS) method could be useful. This review identifies specific antibiotics for which development of DBS methods could support the optimization of treatment of pulmonary infections

Therapeutic drug monitoring in patients with tuberculosis and concurrent medical problems

Introduction Therapeutic drug monitoring (TDM) has been recommended for treatment optimization in tuberculosis (TB) but is only is used in certain countries e.g. USA, Germany, the Netherlands, Sweden and Tanzania. Recently, new drugs have emerged and PK studies in TB are continuing, which contributes further evidence for TDM in TB. The aim of this review is to provide an update on drugs used in TB, treatment strategies for these drugs, and TDM to support broader implementation. Areas covered This review describes the different drug classes used for TB, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), along with their pharmacokinetics, dosing strategies, TDM and sampling strategies. Moreover, the review discusses TDM for patient TB and renal or liver impairment, patients co-infected with HIV or hepatitis, and special patient populations - children and pregnant women. Expert opinion TB treatment has a long history of using 'one size fits all.' This has contributed to treatment failures, treatment relapses, and the selection of drug-resistant isolates. While challenging in resource-limited circumstances, TDM offers the clinician the opportunity to individualize and optimize treatment early in treatment. This approach may help to refine treatment and thereby reduce adverse effects and poor treatment outcomes. Funding, training, and randomized controlled trials are needed to advance the use of TDM for patients with TB

Precision and Personalized Medicine and anti-TB treatment:Is TDM feasible for programmatic use?

Therapeutic Drug Monitoring (TDM) is increasingly recommended to ensure the correct drug dose thereby minimizing adverse events and maximizing regimen efficacy. To facilitate implementation in TB programs, a framework for TDM is urgently needed. TDM is only useful for dose optimization if a patient is on an appropriate regimen guided by drug susceptibility testing. TDM using a targeted approach selecting patients with risk factors for suboptimal drug exposure (e.g. diabetes) or not responding to treatment for drugs with a clear concentration-response relationship may provide the best value for money. Semiquantitative point-of-care tests for detection of low or high drug concentration should be implemented at community level while quantitative assays can be performed at regional or central level. Expanding PK/PD research followed by clinical trials including both clinical outcome as well as cost-effectiveness will increase the level of evidence supporting TDM