Assessment of multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in Sudan; findings and implications

ABSTRACT In high tuberculosis (TB)-burden countries such as China, the diagnosis of multidrug-resistant tuberculosis (MDR-TB) using conventional drug susceptibility testing (DST) takes months, making treatment delay inevitable. Poor outcomes of MDR-TB might be associated with delayed, even inappropriate, treatment. The purposes of this study were to investigate the time to MDR-TB treatment initiation and to assess the association between early treatment and treatment outcomes. Between April 2011 and December 2014, this population-based retrospective cohort study collected the demographic and clinical characteristics and the drug susceptibility profiles of all registered MDR-TB patients in Shanghai, China. The dates of TB and MDR-TB diagnoses, DST performance, and treatment initiation were extracted to calculate the times to treatment. In total, 284 of 346 MDR-TB patients were eligible for analysis, and 68.3% (194/284) had favored outcomes. The median time to treatment initiation from TB diagnosis was 172 days among those with favored outcomes and 190 days among those with poor outcomes. Treatments initiated within 60 days after performing DST (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.22 to 5.36) and empirical treatments (OR, 2.09; 95% CI, 1.01 to 4.32) were positively associated with favored outcomes. Substantial delays to MDR-TB treatment were observed when conventional DST was used. Early treatment predicted favored outcomes. Rapid diagnostic methods should be scaled up and improvements should be made in patient management and information linkage to reduce treatment delay.

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Genetic characterization of N-acetyltransferase 2 variants in acquired multidrug-resistant tuberculosis in Indonesia

Pharmacogenomics ◽

10.2217/pgs-2020-0163 ◽

2021 ◽

Author(s):

Rika Yuliwulandari ◽

Kinasih Prayuni ◽

Intan Razari ◽

Retno W Susilowati ◽

Yenni Zulhamidah ◽

...

Keyword(s):

Multidrug Resistant ◽

Resistance Rate ◽

Published Data ◽

Drug Induced ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Appropriate Treatment ◽

Acetylator Status ◽

Mdr Tb

Background: Owing to the high resistance rate of tuberculosis (TB) to isoniazid, which is metabolized by N-acetyltransferase 2 (NAT2), we investigated the associations between NAT2 variants and multidrug-resistant (MDR)-TB. Materials & methods: The acetylator status based on NAT2 haplotypes of 128 patients with MDR-TB in Indonesia were compared with our published data from patients with anti-TB drug-induced liver injury (AT-DILI), TB and the general population. Results: NAT2*4 was more frequent in the MDR-TB group than in the AT-DILI group, TB controls and general controls. NAT2*4/*4 was significantly more frequent in patients with MDR-TB than in those with AT-DILI. NAT2*5B/7B, *6A/6A and *7B/*7B were detected at lower frequencies in patients with AT-DILI. Rapid acetylators were significantly more frequent in patients with MDR-TB than in those with AT-DILI. Conclusion: These results provide an initial data for optimizing TB treatment in the Indonesian population, and suggest that NAT2 genotyping may help to select appropriate treatment by predicting TB-treatment effect.

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Prevalence and Molecular Characterization of Second-Line Drugs Resistance among Multidrug-ResistantMycobacterium tuberculosisIsolates in Southwest of China

BioMed Research International ◽

10.1155/2017/4563826 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Y. Hu ◽

L. Xu ◽

Y. L. He ◽

Y. Pang ◽

N. Lu ◽

...

Keyword(s):

Gene Mutations ◽

Multidrug Resistant ◽

Rapid Screening ◽

Second Line ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Improper Use ◽

Mdr Tb

This study aimed to investigate the prevalence of multidrug-resistant tuberculosis (MDR-TB) isolates resistant to the second-line antituberculosis drugs (SLDs) and its association with resistant-related gene mutations inMycobacterium tuberculosis(M.tb) isolates from Southwest of China. There were 81 isolates resistant to at least one of the SLDs among 156 MDR-TB isolates (81/156, 51.9%). The rates of general resistance to each of the drugs were as follows: OFX (66/156, 42.3%), KAN (26/156, 16.7%), CAP (13/156, 8.3%), PTO (11/156, 7.1%), PAS (22/156, 14.1%), and AMK (20/156, 12.8%). Therefore, the most predominant pattern was resistant to OFX compared with other SLDs (P<0.001). The results of sequencing showed that 80.2% OFX-resistant MDR-TB isolates containedgyrAmutation and 88.5% KAN-resistant isolates hadrrsmutations with the most frequent mutation being A1401G. These results suggest that improper use of SLDs especially OFX is a real threat to effective MDR-TB treatment not only in China but also in the whole world. Furthermore the tuberculosis control agencies should carry out SLDs susceptibility testing and rapid screening in a broader population of TB patients immediately and the SLDs should be strictly regulated by the administration in order to maintain their efficacy to treat MDR-TB.

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Treatment outcomes in multidrug-resistant tuberculosis according to pyrazinamide susceptibility

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.19.0314 ◽

2020 ◽

Vol 24 (2) ◽

pp. 233-239

Author(s):

S. Park ◽

K-W. Jo ◽

T. S. Shim

Keyword(s):

Success Rate ◽

Treatment Outcomes ◽

Treatment Success ◽

Multidrug Resistant ◽

Treatment Success Rate ◽

Aminosalicylic Acid ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Effective Drugs

BACKGROUND: Pyrazinamide (PZA) is an important anti-tuberculosis drug for multidrug-resistant tuberculosis (MDR-TB). However, PZA has recently been demoted within the hierarchy of TB drugs used for MDR-TB.METHODS: We conducted a retrospective cohort study to investigate treatment outcomes for simple MDR-TB (susceptible to both second-line injectable drugs and fluoroquinolones) according to PZA susceptibility.RESULTS: Among 216 pulmonary MDR-TB patients included in the study, 68 (31.5%) were PZA-resistant (PZA-R). The mean age was 41.8 years, and 63.4% were male. Baseline characteristics such as comorbidity, previous TB history, acid-fast bacilli (AFB) smear positivity and cavitation were similar in PZA-susceptible (PZA-S) and PZA-R patients. The number of potentially effective drugs was slightly higher among PZA-S patients than among the PZA-R (5.1 vs. 4.8, respectively; P = 0.003). PZA was more frequently used in PZA-S patients (73.0%) than in the PZA-R (14.7%), while para-aminosalicylic acid was more frequently used in PZA-R than in PZA-S patients (76.5% vs. 50.7%). The treatment success rate was similar in PZA-S (77.7%) and PZA-R (75.0%) patients. PZA resistance was not associated with treatment success in multivariate analysis.CONCLUSIONS: PZA-resistant simple MDR-TB patients had the same treatment success rate as the PZA-susceptible group even without using novel anti-TB drugs.

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Multidrug-resistant tuberculosis (MDR-TB) and multidrug-resistant HIV (MDR-HIV) syndemic: challenges in resource limited setting

BMJ Case Reports ◽

10.1136/bcr-2019-230628 ◽

2019 ◽

Vol 12 (8) ◽

pp. e230628 ◽

Cited By ~ 1

Author(s):

Christian Francisco ◽

Mary Ann Lansang ◽

Edsel Maurice Salvana ◽

Katerina Leyritana

Keyword(s):

Psoas Abscess ◽

Multidrug Resistant ◽

Health Concern ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Resource Limited ◽

Persons Living With Hiv ◽

Mdr Tb ◽

Living With Hiv

Tuberculosis (TB) is common among persons living with HIV. This public health concern is aggravated by infection with multidrug-resistant organisms and adverse effects of polypharmacy. There are few published cases of multidrug-resistant tuberculosis (MDR-TB) in multidrug-resistant HIV (MDR-HIV) infected patients. We report a case of a 29-year-old Filipino man with HIV on zidovudine (AZT)-containing antiretroviral therapy (ART) but was eventually shifted to tenofovir due to anaemia. He presented with left flank tenderness, which was found to be due to an MDR-TB psoas abscess, and for which second-line anti-TB treatment was started. HIV genotyping showed MDR-HIV infection susceptible only to AZT, protease inhibitors and integrase inhibitors. Subsequently, he developed neck abscess that grew Mycobacterium avium complex and was treated with ethambutol and azithromycin. ART regimen was revised to AZT plus lamivudine and lopinavir/ritonavir. Erythropoietin was administered for recurrent AZT-induced anaemia. Both abscesses resolved and no recurrence of anaemia was noted.

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Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.18.0779 ◽

2019 ◽

Vol 23 (10) ◽

pp. 1050-1054

Author(s):

L. Guglielmetti ◽

J. Jaffré ◽

C. Bernard ◽

F. Brossier ◽

N. El Helali ◽

...

Keyword(s):

Multidrug Resistant ◽

New Drugs ◽

World Health ◽

Advisory Committees ◽

Treatment Regimens ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Health Organization

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

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Task-shifting directly observed treatment and multidrug-resistant tuberculosis injection administration to lay health workers: stakeholder perceptions in rural Eswatini

Human Resources for Health ◽

10.1186/s12960-020-00541-4 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Ernest Peresu ◽

J. Christo Heunis ◽

N. Gladys Kigozi ◽

Diana De Graeve

Keyword(s):

Healthcare Workers ◽

Health Workers ◽

Multidrug Resistant ◽

Task Shifting ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Key Stakeholders ◽

Mdr Tb ◽

Directly Observed Treatment

Abstract Background Eswatini is facing a critical shortage of human resources for health (HRH) and limited access to multidrug-resistant tuberculosis (MDR-TB) treatment in rural areas. This study assessed multiple stakeholders’ perceptions of task-shifting directly observed treatment (DOT) supervision and administration of intramuscular MDR-TB injections to lay health workers (LHWs). Methods A mixed methods study comprising a cross-sectional survey using a semi-structured questionnaire with community treatment supporters (CTSs) and a focus group discussion with key stakeholders including representatives from the Eswatini Ministry of Health (MOH), donor organisations, professional regulatory institutions, nursing academia, civil society and healthcare providers was conducted in May 2017. Descriptive statistics, thematic content analysis and data triangulation aided in the interpretation of results. Results A large majority of CTSs (n = 78; 95.1%) were female and 33 (40.2%) were older than 50 years. Most (n = 7; 70.0%) key stakeholders had over 10 years of work experience in policy-making, advocacy in the fields of HRH or day-to-day practice in MDR-TB management. Task-shifting of MDR-TB injection administration was implemented without national policy guidance and regulation. Stakeholders viewed the strategy to be driven by the prevailing shortage of professional frontline HRH and limited access to MDR-TB treatment. Task-shifting was perceived to improve medication adherence, and reduce stigma and transport-related MDR-TB treatment access barriers. Frontline healthcare workers and implementing donor partners fully supported task-shifting. Policy-makers and other stakeholders accepted task-shifting conditionally due to fears of poor standards of care related to perceived incompetence of CTSs. Appropriate compensation, adequate training and supervision, and non-financial incentives were suggested to retain CTSs. A holistic task-shifting policy and collaboration between the MOH, academia and nursing council in regulating the practice were recommended. Conclusions Stakeholders generally accepted the delegation of DOT supervision and administration of intramuscular MDR-TB injections to LHWs as a strategy to increase access to treatment, albeit with some apprehension. Findings from this study stress that task-shifting is not a panacea for HRH shortages, but a short-term solution that must form part of an overall simultaneous strategy to train, attract and retain adequate numbers of professional healthcare workers in Eswatini. To address some of the apprehension and ambivalence about expanding access to MDR-TB services through task-shifting, attention should be paid to important aspects such as competence-based training, certification and accreditation, adequate supportive on-the-job supervision, recognition, compensation, and expediting policy and regulatory support for LHWs.

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Treatment Outcomes and Adverse Drug Effects of Ethambutol, Cycloserine, and Terizidone for the Treatment of Multidrug-Resistant Tuberculosis in South Africa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00744-20 ◽

2020 ◽

Vol 65 (1) ◽

pp. e00744-20

Author(s):

Martha L. van der Walt ◽

Karen Shean ◽

Piet Becker ◽

Karen H. Keddy ◽

Joey Lancaster

Keyword(s):

Treatment Outcomes ◽

Adverse Drug Events ◽

Drug Effects ◽

Multidrug Resistant ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Default Rates ◽

Conversion Rates ◽

Mdr Tb ◽

Culture Conversion

ABSTRACTTreatment outcomes among multidrug-resistant tuberculosis (MDR-TB) patients receiving ethambutol, cycloserine, or terizidone as part of a standardized regimen were compared, determining occurrence of serious adverse drug events (SADEs). Newly diagnosed adult MDR-TB patients were enrolled between 2000 and 2004, receiving a standardized multidrug regimen for 18 to 24 months, including ethambutol, cycloserine, or terizidone. Cycloserine and terizidone were recorded individually. SADEs and factors associated with culture conversion and unfavorable treatment outcomes (default, death, treatment failure) were determined. Of 858 patients, 435 (51%) received ethambutol, 278 (32%) received cycloserine, and 145 (17%) received terizidone. Demographic and baseline clinical data were comparable. Successful treatment occurred in 56%, significantly more in patients receiving cycloserine (60%) and terizidone (62%) than in those receiving ethambutol (52% [P = 0.03]). Defaults rates were 30% in ethambutol patients versus 15% and 11% for cycloserine and terizidone patients, respectively. Terizidone was associated with fewer unfavorable outcomes (adjusted odds ratio [AOR], 0.4; P = 0.008; 95% confidence interval [CI], 0.2 to 0.8). Patients receiving cycloserine were more likely to achieve culture conversion than those receiving ethambutol or terizidone (AOR, 2.2; P = 0.02; 95% CI, 1.12 to 4.38). Failure to convert increased the odds of unfavorable outcomes (AOR, 23.7; P < 0.001; 95% CI, 13 to 44). SADEs were reported in two patients receiving ethambutol, seven patients receiving cycloserine, and three receiving terizidone (P = 0.05). Ethambutol was associated with high culture conversion and default rates. Cycloserine achieved higher culture conversion rates than terizidone. Fewer patients on terizidone experienced SADEs, with lower default rates. The differences that we observed between cycloserine and terizidone require further elucidation.

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Multidrug-resistant tuberculosis in the Kharkiv Region, Ukraine

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.19.0508 ◽

2020 ◽

Vol 24 (5) ◽

pp. 485-491

Author(s):

D. Butov ◽

C. Lange ◽

J. Heyckendorf ◽

I. Kalmykova ◽

T. Butova ◽

...

Keyword(s):

Treatment Outcomes ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Poor Treatment ◽

Mdr Tb ◽

Observational Cohort

OBJECTIVE: To document the level of drug resistance in MDR-TB patients and to characterize management capacities for their medical care and MDR-TB treatment outcomes in the Kharkiv region of Ukraine. This area has one of the highest frequencies of MDR-TB worldwide.METHODS: A retrospective observational cohort study was performed on registry data from the regional anti-TB dispensary in Kharkiv. All microbiologically confirmed MDR-TB patients registered in 2014 were included. Diagnostic, treatment and post-treatment follow-up data were analysed.RESULTS: Of 169 patients with MDR-TB, 55.0% had pre-extensively drug-resistant (pre-XDR) or XDR resistant patterns. Rapid molecular diagnosis by GeneXpert and liquid M. tuberculosis cultures were only available for 66.9% and 56.8% of patients, respectively. Phenotypic drug-susceptibility testing (DST) for high priority TB drugs (bedaquiline, linezolid, clofazimine) were not available. DST for later generation fluroquinolones was available only in 53.2% of patients. 50.9% of patients had less than 4 drugs in the treatment regimen proven to be effective by DST. More than 23.1% of patients with MDR-TB failed their treatment and only 45.0% achieved a cure.CONCLUSION: The high prevalence of MDR-TB and poor MDR-TB treatment outcomes in the Kharkiv region, is associated with substantial shortages in rapid molecular and phenotypic DST, a lack of high priority MDR-TB drugs, poor treatment monitoring and follow-up capacities.

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An updated systematic review and meta-analysis for treatment of multidrug-resistant tuberculosis

European Respiratory Journal ◽

10.1183/13993003.00803-2016 ◽

2017 ◽

Vol 49 (3) ◽

pp. 1600803 ◽

Cited By ~ 36

Author(s):

Mayara Lisboa Bastos ◽

Zhiyi Lan ◽

Dick Menzies

Keyword(s):

Systematic Review ◽

Treatment Outcomes ◽

Multidrug Resistant ◽

Current Evidence ◽

Aminosalicylic Acid ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

End Of Treatment ◽

Mdr Tb ◽

Culture Conversion

This systematic review aimed to update the current evidence for multidrug-resistant tuberculosis (MDR-TB) treatment.We searched for studies that reported treatment information and clinical characteristics for at least 25 patients with microbiologically confirmed pulmonary MDR-TB and either end of treatment outcomes, 6-month culture conversion or severe adverse events (SAEs). We assessed the association of these outcomes with patients' characteristics or treatment parameters. We identified 74 studies, including 17 494 participants.The pooled treatment success was 26% in extensively drug-resistant TB (XDR-TB) patients and 60% in MDR-TB patients. Treatment parameters such as number or duration and individual drugs were not associated with improved 6-month sputum culture conversion or end of treatment outcomes. However, MDR-TB patients that received individualised regimens had higher success than patients who received standardised regimens (64% versus 52%; p<0.0.01). When reports from 20 cohorts were pooled, proportions of SAE ranged from 0.5% attributed to ethambutol to 12.2% attributed to para-aminosalicylic acid. The lack of significant associations of treatment outcomes with specific drugs or regimens may reflect the limitations of pooling the data rather than a true lack of differences in efficacy of regimens or individual drugs.This analysis highlights the need for stronger evidence for treatment of MDR-TB from better-designed and reported studies.

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