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

Abstract

@ERSpublicationsThe classification of the anti-TB drugs should probably be modified to optimise the use old and new compounds http://ow.ly/QbDSP Multidrug-resistant (MDR) tuberculosis (TB) (resistance to at least isoniazid and rifampicin), with >480 000 cases in 2013, 10% of them being affected by extensively drug-resistant (XDR)-TB (MDR-TB with additional resistance to any fluoroquinolone, and to injectable second-line drugs (SLDs) (capreomycin, kanamycin or amikacin)), continues to represent a real threat to TB control [1][2][3][4]. In some high MDR-TB burden countries, the prevalence of MDR-TB among new cases exceeds 20% and among retreatment cases, reaches almost 50% [1,5].Prevention and quality diagnosis and treatment of MDR-and XDR-TB are part of the crucial interventions included in Pillar 1 of the new World Health Organization (WHO) End TB Strategy, which is focussed on the goal of TB elimination [6][7][8]. Unfortunately, the outcomes of these cases are suboptimal, with 60% success among MDR-TB cases [2], 40% among XDR-TB cases [3] and <20% among the cases with resistance patterns beyond XDR-TB [4]. This means not only high mortality but also significant human suffering and transmission of the Mycobacterium tuberculosis strains within the community [9]. Unfortunately, at present, the treatment of MDR/XDR-TB is still very long, toxic and expensive [10,11].The original WHO guidance on the management of MDR-TB was issued in 1996 [12] and since then, several updated guidelines have been published. The fundamentals on MDR/XDR-TB treatment were published in the 2006 and 2008 WHO guidelines [13,14], where the basic rationale to design therapeutic regimens for these cases was described. According to these recommendations, which are currently followed worldwide, the anti-TB drugs are classified into five main groups indirectly considering the evidence available, the safety and/or the effectiveness of the different drugs. These groups start from the most effective drugs (group 1), grouping the other drugs progressively according to decreasing order of efficacy [15].In the 2011 revision of the WHO MDR/XDR-TB guidelines [16], the composition of different groups of anti-TB drugs was not modified. Therefore, since 2006, the rationale of the classification of the anti-TB drugs has not been changed but several studies have examined the effectiveness, efficacy and safety of the group 5 drugs, and some of these drugs appear to be more effective and well tolerated than others that currently have "higher" ranking in the classification. Furthermore, promising new drugs active against M. tuberculosis have been discovered in the last couple of years [17][18][19][20] and have become progressively available in many parts of the world to treat MDR/XDR-TB.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…These drugs should be considered part of the routine management of highly resistant strains of tuberculosis. 289 Recommendations for the use of bedaquiline and delamanid are outlined in panel 3, mechanisms of action, drug interactions, and key adverse events are described in The Lancet Respiratory Medicine Commission…”

Classification of drugs to treat multidrug-resistant tuberculosis (MDR-TB): evidence and perspectives

“…While bactericidal drugs efficiently reduce the bulk of the rapidly multiplying bacilli (decreasing infectiousness and avoiding the disease's progression), sterilising drugs take care of the population of dormant and semi-dormant bacilli, allowing cure and preventing relapse. The best sterilising drugs may reduce the duration of the treatment while the companion drugs are no longer necessary after bacteriological conversion (2,10,11). When documented resistance or toxicity appears Editorial Classification of drugs to treat multidrug-resistant tuberculosis (MDR-TB): evidence and perspectives for a core drug, it should be replaced by another with a similar efficacy (bactericidal and sterilising).…”

“…At least four drugs likely to be effective compose the regimen, of which at least two are essential (or 'core' drugs), while two are companion drugs (2,10,11). The core drugs are those with the capacity to kill M. tuberculosis in any of its metabolic phases.…”

“…Previous World Health Organization (WHO) guidelines were classifying anti-TB drugs into five main groups, based on a hierarchy of safety and/or the effectiveness considerations (2,7,9). This classification originated in 2006, and updated in 2008, 2011 and, finally, in 2016 based on new evidence, particularly from the former group 5 drugs (10-31).…”

“…Multidrug-resistant (MDR) tuberculosis (TB) (defined as resistance to at least isoniazid and rifampicin), has a relevant epidemiological impact, with 480, 000 cases and 190,000 deaths notified in 2014; 10% of them meet the criteria for extensively drug-resistant (XDR)-TB [MDR-TB with additional resistance to any fluoroquinolone, and to at least one injectable second-line drugs (SLDs)] (capreomycin, kanamycin or amikacin) (1,2).…”