Abstract
The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization, based on lack of evidence, recommends their use under specific conditions and not in combination. No systematic review has yet evaluated the efficacy, safety, and tolerability of delamanid and bedaquiline used in combination. A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of delamanid and bedaquiline-containing regimens in individuals with pulmonary/extrapulmonary disease, which were bacteriologically confirmed as M/XDR-TB. We used PubMed to identify any relevant manuscripts in English up to the 23 December 2016, excluding editorials and reviews. Three out of 75 manuscripts retrieved satisfied the inclusion criteria, whilst 72 were excluded for dealing with only one drug (three studies), being recommendations (one study) or identifying need for their use (one study), focusing on drug resistance aspects (six studies) or being generic reviews/other studies (61 papers). The studies retrieved reported two XDR-TB cases observed for six months and achieving consistent sputum smear and culture conversion. Case 2 experienced a short break of bedaquiline, which was re-started after introducing verapamil. After a transient and symptom-free increase of the QT interval from week 5 to 17, it then decreased below the 500 ms threshold.
Highlights
The new classification includes delamanid and bedaquiline in group D2 [7], their use is recommended under specific conditions in adults [14,15,16]
Delamanid use was recently approved for children above six years of age [16,17]
The main conclusions which can be drawn from this analysis are the following: 1. In extremely challenging M/XDR-TB cases, when the number of drugs are not enough to reach the recommended number of at least four to design an effective regimen, some clinicians have considered using delamanid and bedaquiline in combination
Summary
According to the World Health Organization (WHO), tuberculosis (TB) was responsible for over 10.4 million cases of disease in 2015, 480,000 of whom were affected by multidrug-resistant (MDR)-TB (10% meeting the criteria for extensively drug-resistant (XDR)-TB) and 100,000 by rifampicin-resistant TB, all contributing to an estimated 190,000 deaths [1,2,3,4].The challenges of treating these cases are well known by clinicians operating in MDR-/XDR-TB reference centres, due to the long duration of treatment, the cost of expensive regimens, poor drug tolerability associated with frequent adverse events, and a high treatment failure rate [3,4,5,6,7,8,9,10]. In 2016 the approach to design MDR-TB regimens has changed from the original stepwise approach based on five groups of drugs in priority order [9,11] to a new approach based on the new drugs’ classification [7,12,13]. The new classification includes delamanid and bedaquiline in group D2 [7], their use is recommended under specific conditions in adults (e.g., for six months, at the recommended doses in addition to an optimised background regimen, in the presence of pharmacovigilance and informed consent, under adequate clinical and QT interval monitoring) [14,15,16]. Delamanid use was recently approved for children above six years of age [16,17]
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