Multidrug-resistant tuberculosis in the Kharkiv Region, Ukraine

2020 ◽  
Vol 24 (5) ◽  
pp. 485-491
Author(s):  
D. Butov ◽  
C. Lange ◽  
J. Heyckendorf ◽  
I. Kalmykova ◽  
T. Butova ◽  
...  

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.

2020 ◽  
Author(s):  
Le Hong Van ◽  
Phan Trieu Phu ◽  
Dao Nguyen Vinh ◽  
Vo Thanh Son ◽  
Nguyen Thi Hanh ◽  
...  

Abstract Background: Multidrug resistant tuberculosis (MDR-TB) remains a serious public health problem with poor treatment outcomes. Predictors of poor outcomes vary in different regions. Vietnam is among the top 30 high burden of MDR-TB countries. We describe demographic characteristics and identify risk factors for poor outcome among patients with MDR-TB in Ho Chi Minh City (HCMC), the most populous city in Vietnam.Methods: This retrospective study included 2,266 patients who initiated MDR-TB treatment between 2011-2015 in HCMC. Treatment outcomes were available for 2,240 patients. Data was collected from standardized paper-based treatment cards and electronic records. A Kruskal Wallis test was used to assess changes in median age and body mass index (BMI) over time, and a Wilcoxon test was used to compare the median BMI of patients with and without diabetes mellitus. Chi squared test was used to compare categorical variables. Multivariate logistic regression with multiple imputation for missing data was used to identify risk factors for poor outcomes. Statistical analysis was performed using R program.Results: Among 2,266 eligible cases, 60.2% had failed on a category I or II treatment regimen, 57.7% were underweight, 30.2% had diabetes mellitus and 9.6% were HIV positive. The notification rate increased 24.7% from 2011-2015. The treatment success rate was 73.3%. Risk factors for poor treatment outcome included HIV co-infection (adjusted odds ratio (aOR): 2.94), advanced age (aOR: 1.45 for every increase of 5 years for patients 60 years or older), having history of MDR-TB treatment (aOR: 5.53), sputum smear grade scanty or 1+ (aOR: 1.47), smear grade 2+ or 3+ (aOR: 2.06), low BMI (aOR: 0.83 for every increase of 1kg/m2 of BMI for patients with BMI<21).Conclusion: The number of patients diagnosed with MDR-TB in HCMC increased by almost a quarter between 2011-2015. Patients with HIV, high smear grade, malnutrition or a history of previous MDR-TB treatment are at greatest risk of poor treatment outcome.


2020 ◽  
Vol 24 (3) ◽  
pp. 329-339 ◽  
Author(s):  
J-C. S. Ngabonziza ◽  
Y. M. Habimana ◽  
T. Decroo ◽  
P. Migambi ◽  
A. Dushime ◽  
...  

SETTING: In 2005, in response to the increasing prevalence of rifampicin-resistant tuberculosis (RR-TB) and poor treatment outcomes, Rwanda initiated the programmatic management of RR-TB, including expanded access to systematic rifampicin drug susceptibility testing (DST) and standardised treatment.OBJECTIVE: To describe trends in diagnostic and treatment delays and estimate their effect on RR-TB mortality.DESIGN: Retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality.RESULTS: Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016. Total delay in starting multidrug-resistant TB (MDR-TB) treatment of more than 100 days was associated with more than two-fold higher odds for dying. When delays were long, empirical RR-TB treatment initiation was associated with a lower mortality.CONCLUSION: The reduction of diagnostic and treatment delays reduced RR-TB mortality. We anticipate that universal testing for RR-TB, short diagnostic and therapeutic delays and effective standardised MDR-TB treatment will further decrease RR-TB mortality in Rwanda.


2018 ◽  
Vol 62 (4) ◽  
pp. e02259-17 ◽  
Author(s):  
Yong Chen ◽  
Zhengan Yuan ◽  
Xin Shen ◽  
Jie Wu ◽  
Zheyuan Wu ◽  
...  

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.


2019 ◽  
Author(s):  
Le Hong Van ◽  
Phan Trieu Phu ◽  
Dao Nguyen Vinh ◽  
Vo Thanh Son ◽  
Nguyen Thi Hanh ◽  
...  

Abstract Background: Multidrug resistant tuberculosis (MDR-TB) remains a serious public health problem with poor treatment outcomes. Predictors of poor outcomes vary in different regions. Vietnam is among the top 30 high burden of MDR-TB countries. We describe demographic characteristics and identify risk factors for poor outcome among patients with MDR-TB in Ho Chi Minh City (HCMC), the most populous city in Vietnam. Methods: This retrospective study included 2,266 patients who initiated MDR-TB treatment between 2011-2015 in HCMC. Treatment outcomes were available for 2,240 patients. Data was collected from standardized paper-based treatment cards and electronic records. A Kruskal Wallis test was used to assess changes in median age and body mass index (BMI) over time, and a Wilcoxon test was used to compare the median BMI of patients with and without diabetes mellitus. Chi squared test was used to compare categorical variables. Multivariate logistic regression with multiple imputation for missing data was used to identify risk factors for poor outcomes. Statistical analysis was performed using R program. Results: Among 2,266 eligible cases, 60.2% had failed on a category I or II treatment regimen, 57.7% were underweight, 30.2% had diabetes mellitus and 9.6% were HIV positive. The notification rate increased 24.7% from 2011-2015. The treatment success rate was 73.3%. Risk factors for poor treatment outcome included HIV co-infection (adjusted odds ratio (aOR): 2.94), advanced age (aOR: 1.45 for every increase of 5 years for patients 60 years or older), having history of MDR-TB treatment (aOR: 5.53), sputum smear grade scanty or 1+ (aOR: 1.47), smear grade 2+ or 3+ (aOR: 2.06), low BMI (aOR: 0.83 for every increase of 1kg/m2 of BMI for patients with BMI<21). Conclusion: The number of patients diagnosed with MDR-TB in HCMC increased by almost a quarter between 2011-2015. Patients with HIV, high smear grade, malnutrition or a history of previous MDR-TB treatment are at greatest risk of poor treatment outcome.


2019 ◽  
Vol 23 (12) ◽  
pp. 1257-1262 ◽  
Author(s):  
R. J. Chandak ◽  
B. Malhotra ◽  
S. Bhargava ◽  
S. K. Goel ◽  
D. Verma ◽  
...  

SETTING: Patients with presumed multidrug-resistant tuberculosis (MDR-TB) and undergoing MDR-TB treatment from Rajasthan, India.OBJECTIVE: To compare the GenoType® MTBDRsl v.1.0 (MTBDRsl) assay capacity to detect resistance to ofloxacin, amikacin, capreomycin, kanamycin and ethambutol in Mycobacterium tuberculosis with phenotypic drug susceptibility testing (DST) using MGIT™960™ in sputum samples and isolates.DESIGN: Fifty-three smear-positive sputum samples were tested directly by MTBDRsl and 205 MDR-TB isolates were processed using MTBDRsl and DST for five drugs on MGIT960. DNA sequencing was performed in isolates with discordance in the results between the two methods for the gyrA, gyrB and rrs genes.RESULT: Sensitivity and specificity of MTBDRsl was found to be respectively 93.1% and 100% for fluoroquinoline, respectively 75–78% and 100% for aminoglycosides/cyclopeptides, respectively 70% and 92% for ethambutol and respectively 92.3% and 100% for extensively drug-resistant (XDR) TB detection. On sequencing eight discordant isolates for quinolones, mutations were seen in 12.5% of the gyrB gene and among 20 discordant isolates for aminoglycosides/cyclopeptides in the rrs gene in 15% isolates. The turnaround time was 2 days for MTBDRsl vs. 10 days for MGIT960.CONCLUSIONS: MTBDRsl can be used as an initial rapid test for detecting XDR-TB, resistance to quinolones and aminogycosides/cyclopeptides in smear-positive sputum samples.


Author(s):  
Wan-Hsuan Lin ◽  
Wei-Ting Lee ◽  
Hsing-Yuan Tsai ◽  
Ruwen Jou

Discordant results for Mycobacterium tuberculosis isolates with disputed mutations between genotypic drug susceptibility testing (DST) (gDST) and phenotypic DST (pDST) impact RIF-resistant (RR) and multidrug-resistant (MDR) tuberculosis (TB) treatments due to a lack of practical clinical guidelines. To investigate the role of disputed rpoB mutations in M. tuberculosis and TB treatment outcomes, initial isolates of 837 clinical RR or MDR-TB cases confirmed during 2014-2018 were retested using agar-based RIF pDST and rpoB gene sequencing. Minimum inhibitory concentrations (MICs) were determined for isolates with disputed rpoB mutations. Disputed rpoB mutations were identified in 77 (9.2%) M. tuberculosis isolates, including 50 (64.9%) and 14 (18.2%) phenotypic RIF- and rifabutin (RFB)-resistant isolates, respectively. The predominant single mutations were L533P (44.2%) and L511P (20.8%). Most of the isolates harboring L511P (87.5%), H526N (100%), D516Y (70.0%) and L533P (63.6%) mutations had MICs ≤1 mg/L, whereas isolates harboring H526L (75%) had MICs > 1 mg/L. Of the 63 cases with treatment outcomes, 11 (17.5%) cases died, 1 (1.6%) case transferred out and 51 (81%) cases had favorable outcomes, including 8 and 20 cases treated with standard-dose RIF- and RFB-containing regimens, respectively. Excluding cases transferred out, received no or 1-day treatment, we observed statistically significant differences between active and inactive fluoroquinolones (FQs) [P =0.004, Odds ratio =0.05 (95% confidence intervals, 0.01-0.38)] in 57 cases. We concluded that disputed rpoB mutations are not rare. Depending on resources, sequencing and/or MIC testing is recommended for better management of RR and MDR-TB cases.


2020 ◽  
Vol 51 (6) ◽  
pp. 606-613
Author(s):  
Ye-Cheng Zhou ◽  
Shu-Mei He ◽  
Zi-Lu Wen ◽  
Jun-Wei Zhao ◽  
Yan-Zheng Song ◽  
...  

Abstract Rapid and accurate diagnosis of multidrug-resistant tuberculosis (MDR-TB) is important for timely and appropriate therapy. In this study, a rapid and easy-to-perform molecular test that integrated polymerase chain reaction (PCR) amplification and a specific 96-well microplate hybridization assay, called PCR-ELISA (enzyme-linked immunosorbent assay), were developed for detection of mutations in rpoB, katG, and inhA genes responsible for rifampin (RIF) and isoniazid (INH) resistance and prediction of drug susceptibility in Mycobacterium tuberculosis clinical isolates. We evaluated the utility of this method by using 32 multidrug-resistent (MDR) isolates and 22 susceptible isolates; subsequently, we compared the results with data obtained by conventional drug susceptibility testing and DNA sequencing. The sensitivity and specificity of the PCR-ELISA test were 93.7% and 100% for detecting RIF resistance, and 87.5% and 100% for detecting INH resistance, respectively. These results were comparable to those yielded by commercially available molecular tests such as the GenoType MTBDRplus assay. Based on the aforementioned results, we conclude that the PCR-ELISA microplate hybridization assay is a rapid, inexpensive, convenient, and reliable test that will be useful for rapid diagnosis of MDR-TB, for improved clinical care.


2010 ◽  
Vol 139 (11) ◽  
pp. 1784-1793 ◽  
Author(s):  
H. LIN ◽  
S. SHIN ◽  
J. A. BLAYA ◽  
Z. ZHANG ◽  
P. CEGIELSKI ◽  
...  

SUMMARYWe examined the spatiotemporal distribution of laboratory-confirmed multidrug-resistant tuberculosis (MDR TB) cases and that of other TB cases in Lima, Peru with the aim of identifying mechanisms responsible for the rise of MDR TB in an urban setting. All incident cases of TB in two districts of Lima, Peru during 2005–2007 were included. The spatiotemporal distributions of MDR cases and other TB cases were compared with Ripley's K statistic. Of 11 711 notified cases, 1187 received drug susceptibility testing and 376 were found to be MDR. Spatial aggregation of patients with confirmed MDR disease appeared similar to that of other patients in 2005 and 2006; however, in 2007, cases with confirmed MDR disease were found to be more tightly grouped. Subgroup analysis suggests the appearance of resistance may be driven by increased transmission. Interventions should aim to reduce the infectious duration for those with drug-resistant disease and improve infection control.


2019 ◽  
Author(s):  
Le Hong Van ◽  
Phan Trieu Phu ◽  
Dao Nguyen Vinh ◽  
Vo Thanh Son ◽  
Nguyen Thi Hanh ◽  
...  

Abstract Background: Multidrug resistant tuberculosis (MDR-TB) remains a serious public health problem with poor treatment outcome. Predictors of poor outcomes vary in different regions. Vietnam is among the 30 countries with high burden of MDR-TB. We aim to describe demographic characteristics and identify risk factors for poor outcome of MDR-TB in Ho Chi Minh City (HCMC), the most populous city in Vietnam. Methods: This retrospective study included 2,266 patients who initiated MDR-TB treatment from 2011 to 2015 in HCMC. Treatment outcomes were available in 2,240 patients. Data was collected from standardized paper-based treatment cards and electronic records. Kruskal Wallis test was used to diagnose the change of median of age and body mass index (BMI) over 5 years, and Wilcoxon test to compare median BMI of patients with and without diabetes mellitus. Chi squared test was used to compare categorical variables. Multivariate logistic regression on multiple imputation was used to identify risk factors for poor outcomes. Statistical analysis was performed using R program. Results: Among 2,266 eligible cases, 60.2% were failure of category I or II regimen, 57.7% were underweight, 30.2% had diabetes mellitus and 9.6% were HIV positive. Notification rate increased 24.7% from 2011 to 2015.Treatment success rate was 73.3%. Risk factors for poor treatment outcome included HIV co-infection (adjusted odds ratio (aOR): 2.94), advanced age (aOR: 1.45 for every increase of 5 years for patients 60 years or older), having history of MDR-TB treatment (aOR: 5.53), sputum smear grade scanty and 1+ (aOR: 1.47), smear grade 2+ or 3+ (aOR: 2.06), low BMI (aOR: 0.83 for every increase of 1kg/m2 of BMI for patients with BMI<21). Conclusion: Our study describes the increasing cases of MDR-TB in HCMC during 2011 to 2015. Patients with HIV, high smear grade, malnutrition and history of previous MDR-TB treatment should receive additional care. Keywords: multidrug resistant tuberculosis; retrospective; treatment outcome; risk factors; Vietnam


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255357
Author(s):  
Nguyen Bao Ngoc ◽  
Hoa Vu Dinh ◽  
Nguyen Thi Thuy ◽  
Duong Van Quang ◽  
Cao Thi Thu Huyen ◽  
...  

Objective Management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data. Method We conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence. Results Out of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 [1.91–37.42]), renal dysfunction (HR = 8.46 [1.91–37.42]), alcoholism (HR = 13.28 [5.04–34.99]), and a higher average daily dose of injectable drugs (HR = 1.28 [1.14–1.43]). Conclusion While a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.


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