Dataset Information

The potential use of rifabutin for treatment of patients diagnosed with rifampicin-resistant tuberculosis.

ABSTRACT: Background:Use of the Xpert MTB/RIF assay has increased the number of people diagnosed with rifampicin-resistant tuberculosis (RR-TB), especially in South Africa where Xpert is now the initial diagnostic for individuals with TB symptoms. We hypothesized that a proportion of RR-TB patients determined by Xpert can be treated with a rifabutin-containing regimen. Methods:Rifabutin susceptibility by rpoB mutation was assessed in 349 individuals from South Africa and 172 from Belgium. rpoB polymorphisms were identified by Sanger sequencing. Rifampicin and rifabutin susceptibility was assessed phenotypically. A systematic review was performed to comprehensively collate information on rifabutin susceptibility by rpoB polymorphism. Rifabutin susceptibility was assigned to rpoB polymorphisms based on their positive likelihood ratios and ORs. Results:One hundred and twelve rpoB polymorphisms (67.9% from literature) were identified from all 2045 RR-TB patients, of which 17 polymorphisms could be classified as susceptible/resistant to rifabutin. Eleven polymorphisms were associated with rifabutin susceptibility. The 516GTC mutation was the most common, representing 70% (South Africa) and 76% (Belgium) of all rifabutin-susceptible isolates. At a population level, the 11 polymorphisms associated with rifabutin susceptibility occurred in 33.2% and 16.6% of all South African and Belgian patients diagnosed with RR-TB, respectively. Conclusions:Identification of the exact rpoB polymorphism leading to the diagnosis of RR-TB has the potential to allow inclusion of rifabutin in the treatment regimen of a substantial proportion of RR-TB patients. A randomized controlled trial evaluating the efficacy of a rifabutin-containing TB treatment regimen in these selected patients is needed to provide the evidence required for a change in policy.

SUBMITTER: Whitfield MG

PROVIDER: S-EPMC6148329 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The potential use of rifabutin for treatment of patients diagnosed with rifampicin-resistant tuberculosis.

Whitfield Michael G MG Warren Robin M RM Mathys Vanessa V Scott Lesley L De Vos Elise E Stevens Wendy W Stevens Wendy W Streicher Elizabeth M EM Groenen Guido G Sirgel Frederick A FA Van Rie Annelies A

The Journal of antimicrobial chemotherapy 20181001 10

<h4>Background</h4>Use of the Xpert MTB/RIF assay has increased the number of people diagnosed with rifampicin-resistant tuberculosis (RR-TB), especially in South Africa where Xpert is now the initial diagnostic for individuals with TB symptoms. We hypothesized that a proportion of RR-TB patients determined by Xpert can be treated with a rifabutin-containing regimen.<h4>Methods</h4>Rifabutin susceptibility by rpoB mutation was assessed in 349 individuals from South Africa and 172 from Belgium. r ...[more]

PMID: 29982641

Similar Datasets

Project description:BackgroundSince a meta-analysis showed little or no effect of second-line injectables on treatment success, and using injectables may induce ototoxicity, injectable-free rifampicin-resistant tuberculosis (RR-TB) treatment regimens are recommended. However, acquired resistance preventing activity was overlooked. No previous study assessed the effect of shortening the duration of kanamycin administration to 2 months during the intensive phase of the RR-TB shorter treatment regimen (STR).MethodsRetrospective cohort study of the effect of using 2 months of kanamycin instead of the standard 4(+) months (extension if lack of smear conversion at 4 months) on recurrence (either treatment failure or relapse) and fluoroquinolone acquired drug resistance, in patients treated with a gatifloxacin-based STR in Damien Foundation supported clinics in Bangladesh. Logistic regression was used to estimate associations.ResultsFive of 52 (9.6%) treated with a STR containing two months of kanamycin had recurrence, compared to 21 of 738 (2.8%) patients treated with the standard STR containing 4(+) months of kanamycin (OR 3.7; 95%CI:1.5-10.3). In those with initially fluoroquinolone-susceptible TB, acquired resistance to fluoroquinolone was detected in none of 639 patients treated with 4(+) months of kanamycin and two (4.5%) of 44 treated with two months of kanamycin (OR 75.2; 95%CI:3.6-1592.1).ConclusionTwo months of kanamycin was insufficient to prevent recurrence with acquired resistance to gatifloxacin, the core drug of the most effective RR-TB STR. Injectable mediated resistance prevention is important to reach high effectiveness, to safeguard all treatment options after recurrence, and to prevent the spread of resistant TB. Studies on all-oral regimens should also assess the effect of regimen composition on resistance acquisition. Until evidence shows that other drugs can assure at least the same strong resistance preventing activity of the injectables, it seems wise to continue using this group of drugs, and adapt the regimen if any ototoxicity is detected.

Project description:BACKGROUND:Zimbabwe is one of the thirty countries globally with a high burden of multidrug-resistant tuberculosis (TB) or rifampicin-resistant TB (MDR/RR-TB). Since 2010, patients diagnosed with MDR/RR-TB are being treated with 20-24 months of standardized second-line drugs (SLDs). The profile, management and factors associated with unfavourable treatment outcomes of MDR/RR TB have not been systematically evaluated in Zimbabwe. OBJECTIVE:To assess treatment outcomes and factors associated with unfavourable outcomes among MDR/RR-TB patients registered and treated under the National Tuberculosis Programme in all the district hospitals and urban healthcare facilities in Zimbabwe between January 2010 and December 2015. METHODS:A cohort study using routinely collected programme data. The 'death', 'loss to follow-up' (LTFU), 'failure' and 'not evaluated' were considered as "unfavourable outcome". A generalized linear model with a log-link and binomial distribution or a Poisson distribution with robust error variances were used to assess factors associated with "unfavourable outcome". The unadjusted and adjusted relative risks were calculated as a measure of association. A ?value< 0.05 was considered statistically significant. RESULTS:Of the 473 patients in the study, the median age was 34 years [interquartile range, 29-42] and 230 (49%) were males. There were 352 (74%) patients co-infected with HIV, of whom 321 (91%) were on antiretroviral therapy (ART). Severe adverse events (SAEs) were recorded in 118 (25%) patients; mostly hearing impairments (70%) and psychosis (11%). Overall, 184 (39%) patients had 'unfavourable' treatment outcomes [125 (26%) were deaths, 39 (8%) were lost to follow-up, 4 (<1%) were failures and 16 (3%) not evaluated]. Being co-infected with HIV but not on ART [adjusted relative risk (aRR) = 2.60; 95% CI: 1.33-5.09] was independently associated with unfavourable treatment outcomes. CONCLUSION:The high unfavourable treatment outcomes among MDR/RR-TB patients on standardized SLDs were coupled with a high occurrence of SAEs in this predominantly HIV co-infected cohort. Switching to individualized all oral shorter treatment regimens should be considered to limit SAEs and improve treatment outcomes. Improving the ART uptake and timeliness of ART initiation can reduce unfavourable outcomes.

Project description:BackgroundMultidrug- and rifampicin (RMP)-resistant tuberculosis (MDR/RR-TB) requires prolonged and expensive treatment, which is difficult to sustain in the Colombian health system. This requires the joint action of different providers to provide timely health services to people with TB. Identifying factors associated with unfavorable treatment outcomes in patients with MDR/RR-TB who received drug therapy between 2013 and 2015 in Colombia can help guide the strengthening of the national TB control program.MethodA retrospective cohort study was conducted with all patients who received treatment for MDR/RR-TB between January 2013 and December 2015 in Colombia who were registered and followed up by the national TB control program. A multivariate logistic regression model was used to estimate the associations between the exposure variables with the response variable (treatment outcome).ResultsA total of 511 patients with MDR/RR-TB were registered and followed up by the national TB control program in Colombia, of whom 16 (3.1%) had extensive drug resistance, 364 (71.2%) had multidrug resistance, and 131 (25.6%) had RMP monoresistance. The mean age was 39.9 years (95% confidence interval (CI): 38.5-41.3), most patients were male 285 (64.6%), and 299 (67.8%) were eligible for subsidized health services. The rate of unfavorable treatment outcomes in the RR-TB cohort was 50.1%, with rates of 85.7% for patients with extensive drug resistance, 47.6% for patients with multidrug resistance, and 52.6% for patients with RMP monoresistance. The 511 MDR/RR-TB patients were included in bivariate and multivariate analyses, patients age ≥ 60 years (crude odds ratio (ORc) = 2.4, 95% CI 1.1-5.8; adjusted odds ratio (ORa) = 2.7, 95% CI 1.1-6.8) and subsidized health regime affiliation (ORc = 3.6, 95% CI 2.3-5.6; ORa = 3.4, 95% CI 2.0-6.0) were associated with unfavorable treatment outcomes.ConclusionMore than 50% of the patients with MDR/RR-TB in Colombia experienced unfavorable treatment outcomes. The patients who were eligible for subsidized care were more likely to experience unfavorable treatment outcomes. Those who were older than 60 years were also more likely to experience unfavorable treatment outcomes.

Dataset Information

The potential use of rifabutin for treatment of patients diagnosed with rifampicin-resistant tuberculosis.

Publications

The potential use of rifabutin for treatment of patients diagnosed with rifampicin-resistant tuberculosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure