Clinical management of adults and children with multidrug-resistant and extensively drug-resistant tuberculosis

Abstract

This review informs on the prevention, diagnosis, and clinical management of MDR-TB and XDR-TB.

Recent controversies about MDR and XDR‐TB: Global implementation of the WHO shorter MDR‐TB regimen and bedaquiline for all with MDR‐TB?

“…The use of clofazimine may induce cross‐resistance with bedaquiline leading to the possible rapid emergence of bedaquiline resistance, and compromising XDR‐TB treatment. The current XDR‐TB regimen in many countries, depending on availability and prior resistance profiles, consists of a backbone of bedaquiline, linezolid, clofazimine and P‐amino salicylic acid as core drugs . Patients for whom MDR‐TB treatment with the shorter regimen fails will likely need a substitute for clofazimine, which may be cycloserine/terizidone with a significant adverse event profile and limited data on efficacy and high rates of background resistance (40% compared with 5% for clofazimine in patients with XDR‐TB in some settings) .…”

Why Phenotypic Drug Susceptibility Testing of Mycobacterium tuberculosis to First-Line Drugs is not Sufficient for Proper Management of Drug-Resistant and Multidrug-Resistant tuberculosis?

“…The WHO has further categorized infection with M. tuberculosis strains resistant only to rifampicin and isoniazid without additional resistance to other first-line drugs as uncomplicated MDR-TB. Treatment of uncomplicated MDR-TB is easier and success rate for uncomplicated MDR-TB is higher compared to treatment of MDR-TB resistant to additional first-line drugs [5,7,10]. Globally, treatment success rates for TB, MDR-TB and XDR-TB have been recorded as 83%, 54%, and 30%, respectively [2].…”

“…Several (>50) countries have also started using newer (bedaquiline and delamanid) drugs in treatment regimens for MDR/XDR-TB [2]. Unsuccessful treatment of MDR-TB is also a risk factor for XDR-TB, which is very difficult to treat in most of the developing countries [5,7,10].…”

“…Compared to fully drug-susceptible (pansusceptible)-TB, treatment of patients with DR-TB and MDR-TB is much more difficult due to lengthy (9-24 months), more expensive and more toxic drug regimens and the patients often experience clinical failure or disease relapse [5,7,10]. The WHO has further categorized infection with M. tuberculosis strains resistant only to rifampicin and isoniazid without additional resistance to other first-line drugs as uncomplicated MDR-TB.…”

“…Recent studies have shown that patients infected with embB mutants should be considered as having ethambutol-resistant TB even if the isolates appear to be ethambutol-susceptible by phenotypic DST methods to avoid evolution of secondary mutations and selection of fully drug-resistant strains [22,39,40]. False susceptibility to ethambutol is not critical for the treatment of drug-susceptible TB, however, it is detrimental for successful treatment of MDR-TB as drug regimens for this disease entity should not include ineffective first-line drugs [5,7,10,44]. Hybridization-based assays include GeneXpert MTB/RIF assay for the diagnosis of active TB disease and its resistance to rifampicin [2,19,47].…”