Effectiveness and Safety of a Shorter Treatment Regimen in a Setting with a High Burden of Multidrug-Resistant Tuberculosis

Abstract

Treatment of drug-resistant tuberculosis is lengthy, insufficiently effective, and toxic. Since 2016, the World Health Organization has recommended shorter treatment regimens (STR). We assessed effectiveness and predictors of drug adverse events (DAE) among patients treated with STR. There were 95 consecutive rifampicin-resistant patients enrolled in STR in Tashkent between June 2018 and September 2019. Of these, 66.3% were successfully treated, 17.9% suffered failed treatment, 7.4% died, 5.3% were lost to follow-up and 3.2% were not evaluated. No recurrence was identified in 54 patients after 12 months of successful treatment completion. There were 47 reported DAE: the incidence rate was 6.15 DAE per 100 person-months-of-treatment. Any DAE was reported in 38 (40%) patients and grade 3/4 DAE were recorded in 21 (22.1%) patients. Median time to DAE was 101 (interquartile range 64–139) days. The most frequently encountered DAE were gastro-intestinal disorders, followed by hepatotoxicity and ototoxicity. The most commonly offending drug inducing DAE was protionamide. The dose was temporarily interrupted in 55.3% of DAE, reduced in 8.5% of DAE and permanently withdrawn in another 8.5% of DAE. HIV status was the only predictor associated with increased hazard of DAE. In Uzbekistan STR showed moderate effectiveness and safety, although treatment failure was high.

Factors associated with treatment outcome of MDR/RR-TB patients treated with shorter injectable based regimen in West Java Indonesia

“…The results showed that the success rate of the short-term treatment regimen was higher than that longer regimen [8]. Many studies have shown a varying success rate of shorter regimen treatment, between 44.3%-83.7% [9][10][11]. Given this varied range of success rate, our study aimed to identify the success rate and factors associated with the outcome of shorter injectable based regimens in MDR-TB patients in West Java province, Indonesia.…”

Molecular Analysis of Streptomycin Resistance Genes in Clinical Strains of Mycobacterium tuberculosis and Biocomputational Analysis of the MtGidB L101F Variant

“…Precise identification of such strains demands bacterial confirmation and drug resistance assessment using culture methods, molecular analysis and DNA sequencing [5,6]. Moreover, patients with MDR-TB require intensive treatment for at least nine months (up to 20 months), supported by constant pharmacovigilance to reduce adverse events [7,8].…”

Factors Associated with Unfavourable Treatment Outcomes in Patients with Tuberculosis: A 16-Year Cohort Study (2005–2020), Republic of Karakalpakstan, Uzbekistan

“…When used in carefully selected MDR-TB patients who have not been previously exposed to nor have resistance to second-line drugs, these regimens have been reported to achieve relapse-free cures in over 85% of cases, even under programmatic conditions. In 2016, on the basis of data from observational studies of the shorter regimens in different Asian and African countries, the WHO recommended a standardized shorter MDR-TB regimen based on the regimens under study for eligible patients [ 12 , 36 , 37 ].…”

“…However, starting from 2016, Xpert MTB/RIF (a molecular diagnostic assay) has become the first test of choice in all regions of Uzbekistan [ 11 ]. In addition, it is now recommended that patients are considered for chest radiography and mycobacterial culture as part of the diagnostic work-up [ 12 ]. While people with TB are diagnosed and registered in the district TB dispensary, patients can choose between two types of treatment, the inpatient and outpatient modalities, respectively.…”

“…Drug-susceptible and drug-resistant TB patients receive anti-tuberculosis treatment in accordance with National TB treatment protocols which are aligned with the latest WHO recommendations. In some regions of Uzbekistan, short treatment regimens for drug-resistant TB are also being introduced as pilot projects, with this initiative having started in 2018 [ 12 ]. Standardized “conventional” treatment for MDR-TB has been available countrywide since 2013, being first started in the Republic of Karakalpakstan in 2003 with support from Medecins Sans Frontieres (MSF).…”