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Rifampicin Resistant Tuberculosis in Lesotho: Diagnosis, Treatment Initiation and Outcomes.

ABSTRACT: The Lesotho guidelines for the management of drug-resistant tuberculosis (TB) recommend initiation of patients diagnosed with rifampicin resistant (RR)-TB on a standardized drug resistant regimen while awaiting confirmation of rifampicin resistant TB (RR-TB) and complete drug susceptibility test results. Review of diagnostic records between 2014 and 2016 identified 518 patients with RR-TB. Only 314 (60.6%) patients could be linked to treatment records at the Lesotho MDR hospital. The median delay in treatment initiation from the availability of Xpert MTB/RIF assay result was 12 days (IQR 7-19). Only 32% (101) of patients had a documented first-line drug resistant test. MDR-TB was detected in 56.4% of patients while 33.7% of patients had rifampicin mono-resistance. Only 7.4% of patients assessed for second-line resistance had a positive result (resistance to fluoroquinolone). Treatment success was 69.8%, death rate was 28.8%, loss to follow up was 1.0%, and 0.4% failed treatment. Death was associated with positive or unavailable sputum smear at the end of first month of treatment (Fisher exact p < 0.001) and older age (p = 0.007). Urgent attention needs to be given to link patients with RR-TB to care worldwide. The association of death rate with positive sputum smear at the end of the first month of treatment should trigger early individualization of treatment.

SUBMITTER: Katende B

PROVIDER: S-EPMC7002499 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Rifampicin Resistant Tuberculosis in Lesotho: Diagnosis, Treatment Initiation and Outcomes.

Katende Bulemba B Esterhuizen Tonya M TM Dippenaar Anzaan A Warren Robin M RM

Scientific reports 20200205 1

The Lesotho guidelines for the management of drug-resistant tuberculosis (TB) recommend initiation of patients diagnosed with rifampicin resistant (RR)-TB on a standardized drug resistant regimen while awaiting confirmation of rifampicin resistant TB (RR-TB) and complete drug susceptibility test results. Review of diagnostic records between 2014 and 2016 identified 518 patients with RR-TB. Only 314 (60.6%) patients could be linked to treatment records at the Lesotho MDR hospital. The median dela ...[more]

PMID: 32024860

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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:Rifampicin-resistant tuberculosis (RR-TB) is largely underdetected in Indonesia. Xpert MTB/RIF (Xpert) has recently been introduced, prioritizing patients at risk of RR-TB, followed by phenotypic drug-susceptibility (DST) if rifampicin resistance is detected. OBJECTIVE:This study investigated Xpert-based management of presumptive RR-TB cases under routine practice in West Java, Indonesia. METHODS:We examined all records of patients tested with Xpert in the referral hospital for West Java in 2015-2016. We measured loss across a limited cascade of care, time to Xpert diagnosis and the commencement of initial second-line treatment, and identified factors associated with diagnostic and treatment delay. Additionally, we analyzed the appropriateness of treatment according to DST results. RESULTS:Of 3415 patients with presumptive RR-TB, 3215 (94%) were tested by Xpert, of whom 339 (10.5%) were diagnosed as RR-TB. 288 (85%) of 339 RR-TB patients started initial second-line TB treatment, with 48 (14%) patients being lost between diagnosis and pre-treatment assessment. Second-line treatment was commenced at a median of 41 days (IQR 29-70) after RR-TB diagnosis. Delays in both diagnosis and treatment initiation were observed in 104 (52%) of 201 RR-TB patients with identifiable referral date. Rural residence was associated with delay to diagnosis (adjusted OR 2.7; 95%CI 1.5-5.2) and treatment initiation (adjusted OR 2.0; 1.2-3.4). Of 162 patients with available DST result, 107 (66%) had multidrug-resistant tuberculosis (MDR-TB) and 32 (20%) had either pre-extensively drug resistant (pre-XDR) or extensively drug resistant tuberculosis (XDR-TB). We estimated that with the current algorithm 41% of pre-XDR or XDR-TB patients are diagnosed, and 33% of them started on an appropriate treatment regimen. CONCLUSIONS:Many patients with Xpert-diagnosed RR-TB either do not start MDR-TB treatment or encountered diagnostic and treatment delays under programmatic conditions in Indonesia, and most pre-XDR and XDR-TB cases remain undiagnosed. Further expansion and ongoing quality improvement of RR-TB services are urgently needed.

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 𝑝value< 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:BackgroundThere was a complete lack of information about the treatment outcomes of rifampicin/multidrug resistant (RR/MDR) childhood TB patients (age ≤ 14 years) from Pakistan, an MDR-TB 5th high burden country. Therefore, this study evaluated the socio-demographic characteristics, drug resistance pattern, treatment outcomes and factors associated with unsuccessful outcomes among childhood RR/MDR-TB patients in Pakistan.MethodsThis was a multicentre retrospective record review of all microbiologically confirmed childhood RR/MDR-TB patients (age ≤ 14 years) enrolled for treatment at seven units of programmatic management of drug-resistant TB (PMDT) in Pakistan. The baseline and follow-up information of enrolled participants from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. World Health Organization (WHO) defined criterion was used for deciding treatment outcomes. The outcomes of "cured" and "treatment completed" were collectively grouped as successful, whereas "death", "treatment failure" and "lost to follow-up" were grouped together as unsuccessful outcomes. Multivariable binary logistic regression analysis was used to find factors associated with unsuccessful outcomes. A p-value < 0.05 reflected statistically significant findings.ResultsA total of 213 children RR/MDR-TB (84 RR and 129 MDR-TB) were included in the study. Majority of them were females (74%), belonged to the age group 10-14 years (82.2%) and suffered from pulmonary TB (85.9%). A notable proportion (37.1%) of patients had no history of previous TB treatment. Patients were resistant to a median of two drugs (interquartile range: 1-4) and 23% were resistant to any second line anti-TB drug. A total of 174 (81.7%) patients achieved successful treatment outcomes with 144 (67.6%) patients being cured and 30 (14.1%) declared treatment completed. Among the 39 (18.3%) patients with unsuccessful outcomes, 35 (16.4%) died and 4 (1.9%) experienced treatment failure. In multivariable analysis, the use of ethambutol had statistically significant negative association with unsuccessful outcomes (odds ratio = 0.36, p-value = 0.02).ConclusionsIn this study, the WHO target of successful treatment outcomes (≥ 75%) among childhood RR/MDR-TB patients was achieved. The notable proportion of patients with no history of previous TB treatment (37.1%) and the disproportionately high number of female patients (74%) respectively stress for infection control measures and provision of early and high quality care for female drug susceptible TB patients.

Dataset Information

Rifampicin Resistant Tuberculosis in Lesotho: Diagnosis, Treatment Initiation and Outcomes.

Publications

Rifampicin Resistant Tuberculosis in Lesotho: Diagnosis, Treatment Initiation and Outcomes.

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