Therapeutic drug management: is it the future of multidrug-resistant tuberculosis treatment?

Abstract

@ERSpublications TDM can be helpful for multidrug-resistant tuberculosis therapeutic decisions. DBS can bypass logistical issues http://ow.ly/otsFp Multidrug-and extensively drug-resistant (M/XDR) tuberculosis (TB) are emerging public health concerns [1,2]. In 2011, the World Health Organization (WHO) estimated 12 million prevalent cases of TB globally, which is equivalent to 170 cases per 100 000 population, out of these an estimated 630 000 cases were affected by MDR Mycobacterium tuberculosis strains [3]. Among the newly diagnosed patients ,3.7% were infected by MDR-TB strains, but the worrisome fact is that the prevalence of MDR-TB among new cases in some Former Soviet Union countries exceeds 30% [4,5], XDR-TB has been identified in 84 countries and the average proportion of MDR-TB cases with an XDR-TB pattern is 9.0% [3]. Further adding to the problem are the reports of ''totally drug resistant'' TB [6,7], a term currently not recognised by WHO [8,9].Treatment of drug resistant TB is more expensive and more toxic if compared with that prescribed for drugsusceptible TB, and currently takes up to 2 years of therapy [10]. The cost per patient to treat MDR-TB cases is incredibly high [11,12] and, in spite of international public health efforts, the treatment outcome is not very promising [13][14][15]. DIEL et al. [16] showed that direct treatment-related costs of MDR-TB patients can amount to J52 259 in Germany (table 1).In the largest MDR-TB cohort analysed to date [13] the proportion of cases treated successfully was 62%, with 7% failing or relapsing, 9% dying and 17% defaulting; in the XDR-TB subgroup 40% achieved treatment success, 22% failed treatment or relapsed, whereas 15% died and 16% defaulted [14,15].In this issue of the European Respiratory Journal (ERJ) a Dutch group from Groningen [17] reported on the results of a prospective pharmacokinetic (PK) study aimed at quantifying the effect of clarithromycin on the exposure to linezolid. In simple terms they observed that clarithromycin, which has some activity against TB bacilli and is well tolerated, increases linezolid exposure (i.e. increases the blood levels of linezolid, which is a very expensive and toxic drug). The authors decided to quantify this phenomenon administering a fix dose of linezolid (300 mg twice a day) plus a variable one of clarithromycin (250-500 mg once a day).Using validated PK methods they demonstrated that linezolid exposure significantly increased after the coadministration of 500 mg clarithromycin by a median (interquartile range) of 44% (23-102%), when

Classification of antituberculosis drugs: a new proposal based on the most recent evidence

“…With regard to toxicity, a reduced initial linezolid dose or a dose adjustment during treatment (e.g. using the therapeutic drug monitoring (TDM) approach) has shown to improve tolerance without affecting efficacy [30,36,[39][40][41][42]. In fact, adverse events are lower when a linezolid dose of 300 mg·day −1 is used [40].…”

Bedaquiline: 10 years later, the drug susceptibility testing protocol is still pending

“…Third, the scientific community needs to share all existing pieces of information deriving from the use of this new drug in order to have better information on its safety and efficacy. Finally, bedaquiline needs to be more widely accessible in order to evaluate best protocols for DST, MIC analyses and protocols for therapeutic drug monitoring [23][24][25]. In the original 2005 Science article, DST was performed using the radiometric BACTEC 460TB, which has since been discontinued.…”

Multidrug-resistant and extensively drug-resistant tuberculosis: a review of current concepts and future challenges

“…So far, data on TDM in TB treatment are scarce, cost is high and adequate know-how exists only from a few centres. 37 Currently, a methodology using dry blood-spot tests has been established to make TDM more accessible, 38 but critical data on pharmacokinetics and pharmacodynamics of anti-TB drugs remain unknown.…”