scholarly journals Epidemiology of HIV-negative Rifampicin Resistance /Multidrug-Resistant Extrapulmonary Tuberculosis: 5 Years-experience From a National Tuberculosis Clinical Research Center in China

2021 ◽  
Author(s):  
Jun Ma ◽  
Lin Fan ◽  
Hongcheng Liu ◽  
Wenting Li ◽  
Wenwen Sun
Keyword(s):  
Early Stage ◽  
Extrapulmonary Tuberculosis ◽  
Multidrug Resistant ◽  
Rifampicin Resistance ◽  
Anatomical Site ◽  
Successful Treatment Outcome ◽  
National Tuberculosis ◽  
Control Programmes ◽  
Mdr Tb ◽  
Positive Rate

Abstract Background: China is a region with a high global burden of Rifampicin Resistance ／Multidrug-Resistant tuberculosis (RR/MDR-TB) and low HIV incidence. Our aim was to assess the epidemiological and clinical characteristics of RR/MDR-extrapulmonary tuberculosis (EPTB) over the past five years in China to inform national TB control programmes.Methods: We investigated the epidemiological and clinical datas of all MDR/RR-EPTB cases in a TB specialized hospitals in China over a five-year period and compared cases with a cohort of MDR/RR-PTB patients over the same period.Results: Of the 1,700 RR/MDR-TB patients enrolled, 17.76% were EPTB. The incidence of RR／MDR-EPTB were increasing.The most common anatomical site was pleura/chest wall (20.20%). Compared with RR／MDR-Pulmonary tuberculosis (PTB），RR/MDR-EPTB were were predominately female (50.66%, P< 0.01) 、more prone to delay (P<0.01) in RR/ MDR-EPTB detection with the median time of 145（14 ,341）days since first visit、more less likely to develop diabetes (22.85 %, P<0.01) 、more likely to be newly diagnosed ( 56.95%, P<0.01) 、lower successful treatment outcome（69.56%，p <0.01）、more dependent on Xpert (93.71%) for resistance detection、lower culture positive rate (56.95% , P< 0.01). RR/ MDR-EPTB also showed a significantly higher rate of pre-XDR/XDR (32.45%, P <0.01) . Conclusion: RR/MDR-EPTB is different from RR-MDR/PTB in both epidemiology and clinical. Clinicians should recommend Xpert in early stage and use fluoroquinolones cautiously in cases suspected TB.

scholarly journals Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Natasha F. Sabur ◽  
Mantaj S. Brar ◽  
Lisa Wu ◽  
Sarah K. Brode
Keyword(s):  
Hearing Loss ◽  
Adverse Events ◽  
Low Dose ◽  
Multidrug Resistant ◽  
Significant Rise ◽  
World Health ◽  
Therapeutic Drug ◽  
Successful Treatment Outcome ◽  
Mdr Tb ◽  
Health Organization

Abstract Background The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15 mg/kg. However, higher doses are associated with significant toxicity. Methods Patients with MDR-TB treated at our institution receive amikacin at 8–10 mg/kg, with dose adjustment based on therapeutic drug monitoring. We conducted a retrospective cohort study of patients with MDR-TB who received amikacin between 2010 and 2016. Results Forty-nine patients were included in the study. The median starting dose of amikacin was 8.9 mg/kg (IQR 8, 10), and target therapeutic drug levels were achieved at a median of 12 days (IQR 5, 26). The median duration of amikacin treatment was 7.2 months (IQR 5.7, 8), and median time to sputum culture conversion was 1 month (IQR 1,2). Six patients (12.2%) experienced hearing loss based on formal audiometry testing (95% CI 4.6–24.8%); 22.2% had subjective hearing loss (95% CI 11.2–37.1%) and 31.9% subjective tinnitus (95% CI 19.1–47.1%). Ten patients (23%) had a significant rise in serum creatinine (95% CI 11.8–38.6%), but only 5 patients had a GFR < 60 at treatment completion. 84% of patients had a successful treatment outcome (95% CI 84–99%). Conclusions Low dose amikacin is associated with relatively low rates of aminoglycoside-related adverse events. We hypothesize that low-dose amikacin can be used as a safe and effective treatment for MDR-TB in situations where an adequate regimen cannot be constructed with Group A and B drugs, and where careful monitoring for adverse events is feasible.

scholarly journals Multidrug-resistant tuberculosis in the United States, 2011–2016: patient characteristics and risk factors

2020 ◽  
Vol 24 (1) ◽  
pp. 92-99 ◽  
Author(s):  
M. P. Chen ◽  
R. Miramontes ◽  
J. S. Kammerer
Keyword(s):  
United States ◽  
Risk Factors ◽  
Patient Characteristics ◽  
The United States ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Recent Transmission ◽  
National Tuberculosis ◽  
Mdr Tb

OBJECTIVE: To determine risk factors for multidrug-resistant tuberculosis (MDR-TB) and describe MDR-TB according to three characteristics: previous TB disease, recent transmission of MDR-TB, and reactivation of latent MDR-TB infection.SETTING and DESIGN: We used 2011–2016 surveillance data from the US National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service and used logistic regression models to estimate risk factors associated with MDR-TB.RESULTS: A total of 615/45 209 (1.4%) cases were confirmed as MDR-TB; 111/615 (18%) reported previous TB disease; 41/615 (6.7%) were attributed to recent MDR-TB transmission; and 449/615 (73%) to reactivation. Only 12/41 (29%) patients with TB attributed to recent transmission were known to be contacts of someone with MDR-TB. For non-US-born patients, the adjusted odds ratios of having MDR-TB were 32.6 (95%CI 14.6–72.6) among those who were known to be contacts of someone with MDR-TB and 6.5 (95%CI 5.1–8.3) among those who had had previous TB disease.CONCLUSION: The majority of MDR-TB cases in the United States were associated with previous TB disease or reactivation of latent MDR-TB infection; only a small proportion of MDR-TB cases were associated with recent transmission.

scholarly journals Evolutionary trajectories and transmission dynamics of multidrug-resistant Mycobacterium tuberculosis in Tibet, China

2021 ◽  
Author(s):  
Qi Jiang ◽  
Hai-can Liu ◽  
Qing-yun Liu ◽  
Jody E. Phelan ◽  
Li Shi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Phylogenetic Trees ◽  
Multidrug Resistant ◽  
Rifampicin Resistance ◽  
Whole Genome Sequencing Data ◽  
High Burden ◽  
Increased Risk ◽  
Mdr Tb ◽  
Resistant Strains ◽  
The Impact

ABSTRACTObjectiveTibet has the highest prevalence of both tuberculosis disease and multidrug-resistant tuberculosis (MDR-TB) in China. The circulated Mycobacterium tuberculosis strains from Tibet were sequenced to investigate the underlying drivers for the high burden of MDR-TB.MethodsUsing whole-genome sequencing data of 576 M. tuberculosis strains isolated from consecutive patients in Tibet, we mapped resistance-conferring mutations onto phylogenetic trees to determine their evolution and spread. The impact of drug resistance on bacterial population growth was assessed with a Bayesian (Skyline Plot) analysis. Multivariable logistic regression was used to identify risk factors for the development of rifampicin resistance.ResultsOf the 576 isolates, 284 (49.3%), 280 (48.6%), and 236 (41.0%) were, respectively, genetically resistant to isoniazid, rifampicin, or both (MDR-TB). Among the isoniazid- and rifampicin-resistant strains, the proportions in phylogenetically-inferred clusters were 77.8% (221/284) and 62.1% (174/280), respectively. Nearly half (47.2%, 134/284) of the isoniazid-resistant strains were in six major clades, which contained between 8 and 58 strains with katG S315T, katG S315N, or fabG1 promoter −15 C>T resistance mutations. These major clades exponentially expanded after emerging with isoniazid resistance and stabilized before evolving into MDR-TB twenty years later. Isoniazid-resistant isolates showed an increased risk of accumulating rifampicin resistance compared to isoniazid-susceptible strains, with an adjusted odds ratio of 3.81 (95% confidence interval 2.47-5.95).ConclusionHistorical expansion of isoniazid-resistant strains and their increased likelihood of acquiring rifampicin resistance both contributed to the high burden of MDR-TB in Tibet, highlighting the need to detect INH-resistant strains promptly and to control their transmission.

scholarly journals Patient- and provider-related factors in the success of multidrug-resistant tuberculosis treatment in Colombia

2021 ◽  
Vol 45 ◽  
pp. 1
Author(s):  
Gloria Mercedes Puerto Castro ◽  
Fernando Nicolás Montes Zuluaga ◽  
Jacqueline Elizabeth Alcalde-Rabanal ◽  
Freddy Pérez
Keyword(s):  
Treatment Outcome ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Insurance Scheme ◽  
Related Factors ◽  
Successful Treatment Outcome ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Nursing Professionals

Objective. To identify patient- and provider-related factors associated with the success of multidrug-resistant tuberculosis (MDR-TB) treatment in the six municipalities of Colombia with the highest number of MDR-TB cases. Methods. Bivariate and multivariate logistic regressions were used to analyze the association between treatment success (cure or treatment completion) and characteristics of the patients and physicians, nursing professionals, and psychologists involved in their treatment. The importance of knowledge in the management of MDR-TB cases was explored through focus groups with these providers. Results. Of 128 cases of TB-MDR, 63 (49.2%) experienced treatment success. Only 52.9% of the physicians and nursing professionals had satisfactory knowledge about MDR-TB. Logistic regression showed that being HIV negative, being affiliated with the contributory health insurance scheme, being cared for by a male physician, and being cared for by nursing professionals with sufficient knowledge were associated with a successful treatment outcome (p ≤ 0.05). Qualitative analysis showed the need for in-depth, systematic training of health personnel who care for patients with MDR-TB. Conclusion. Some characteristics of patients and healthcare providers influence treatment success in MDR-TB cases. Physicians’ and nurses’ knowledge about MDR-TB must be improved, and follow-up of MDR-TB patients who are living with HIV and of those affiliated with the subsidized health insurance scheme in Colombia must be strengthened, as these patients have a lower likelihood of a successful treatment outcome.

scholarly journals Tuberculosis in Europe: another step forward for international surveillance

1998 ◽  
Vol 3 (1) ◽  
pp. 2-5
Author(s):  
Collective Editorial team
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pilot Study ◽  
Relative Effectiveness ◽  
Multidrug Resistant ◽  
Case Definitions ◽  
Specific Data ◽  
Reporting Systems ◽  
National Tuberculosis ◽  
Control Programmes ◽  
Resistant Strains

Spurred on by the reversal or slowing of the decline in tuberculosis incidence in many countries, the threat of the emergence of multidrug resistant strains of Mycobacterium tuberculosis, and possibly by the success of international AIDS surveillance, European collaborators have completed a pilot study (reported in this issue) of the feasibility of standardising tuberculosis surveillance. Although the case definitions used within countries differ, these differences are unlikely to account for the large variations in the incidence of tuberculosis between countries, ranging in 1995 from 3 per 100 000 in Malta to 102/100 000 in Romania. Equally large differences between countries were observed for the proportions of cases who had been born abroad. The establishment of surveillance for Europe as a whole is likely to strengthen national tuberculosis reporting systems and enable multidrug resistance and the relative effectiveness of control programmes to be monitored closely. When standardised case specific data are shared routinely more sophisticated analyses will be possible, which should enable prevention policies to be selected that will hasten the elimination of “the captain of all these men of death”.

scholarly journals Surveillance of Rifampicin Resistance With GeneXpert MTB/RIF in the National Reference Laboratory for Tuberculosis at the Institut Pasteur in Bangui, 2015–2017

2019 ◽  
Vol 6 (3) ◽  
Author(s):  
Alain Farra ◽  
Alexandre Manirakiza ◽  
Brice Martial Yambiyo ◽  
Germain Zandanga ◽  
Boris Lokoti ◽  
...  
Keyword(s):  
Central African Republic ◽  
Multidrug Resistant ◽  
Population Surveillance ◽  
Rifampicin Resistance ◽  
Reference Laboratory ◽  
Chi Square ◽  
Significant Difference ◽  
Mdr Tb ◽  
The Mean ◽  
Surveillance Database

Abstract Background The Central African Republic (CAR) has one of the heaviest burdens of tuberculosis (TB) in the world, with an incidence of 423 cases per 100 000 population. Surveillance of resistance to rifampicin with GeneXpert MTB/RIF was instituted in the National TB Reference Laboratory in 2015. The aim of this study was to evaluate, after 3 years, resistance to rifampicin, the most effective firstline drug against TB. Methods The surveillance database on cases of rifampicin resistance was retrospectively analyzed. The populations targeted by the National TB Programme were failure, relapse, default, and contacts of multidrug-resistant TB (MDR-TB). Statistical analyses were performed with Stata software, version 14, using chi-square tests and odds ratios. Results Six hundred seventeen cases were registered; 63.7% were male, 36.3% were female, and the mean age was 35.5 years (range from 2 to 81). GeneXpert MTB/RIF tests were positive in 79.1% (488/617), and resistance to rifampicin was positive in 42.2% (206/488), with 49.1% (56/114) in 2015, 34.7% (57/164) in 2016, and 44.3% (93/210) in 2017. Failure cases had the highest rate of resistance (70.4%), with a significant difference (P &lt; .0001; odds ratio, 9.5; 95% confidence interval, 4.4–20.5). Resistance was observed in 40% of contacts of MDR-TB, 28.2% of the relapses and 20% of the defaults without significant difference. Conclusions Resistance to rifampicin is still high in the CAR and is most strongly associated with treatment failure. The Ministry of Health must to deploy GeneXpert MTB/RIF tests in the provinces to evaluate resistance to TB drugs in the country.

scholarly journals Rifampicin mono-resistant tuberculosis is not the same as multidrug-resistant tuberculosis: a descriptive study from Khayelitsha, South Africa

2021 ◽  
Author(s):  
Zubeida Salaam-Dreyer ◽  
Elizabeth M. Streicher ◽  
Frederick A. Sirgel ◽  
Fabrizio Menardo ◽  
Sonia Borrell ◽  
...  
Keyword(s):  
South Africa ◽  
Critical Concentration ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Rifampicin Resistance ◽  
Potential Contribution ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
High Level

Rifampicin mono-resistant TB (RMR-TB, rifampicin resistance and isoniazid susceptibility) constitutes 38% of all rifampicin-resistant TB (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-TB) within a high TB, RR-TB and HIV burden setting. Patient-level clinical data and stored RR-TB isolates from 2008-2017 with available whole genome sequencing (WGS) data were used to describe risk factors associated with RMR-TB and to compare rifampicin-resistance (RR) conferring mutations between RMR-TB and MDR-TB. A subset of isolates with particular RR-conferring mutations were subjected to semi-quantitative rifampicin phenotypic drug susceptibility testing. Among 2,041 routinely diagnosed RR-TB patients, 463 (22.7%) had RMR-TB. HIV-positive individuals (adjusted Odds Ratio 1.4, 95% CI 1.1-1.9) and diagnosis between 2013-2017 versus 2008-2012 (aOR 1.3, 1.1-1.7) were associated with RMR-TB. Among 1,119 (54.8%) patients with available WGS data showing RR-TB, significant differences in the distribution of rpoB RR-conferring mutations between RMR-TB and MDR-TB isolates were observed. Mutations associated with high-level RR were more commonly found among MDR-TB isolates (811/889, 90.2% versus 162/230, 70.4% among RMR-TB, p<0.0001). In particular, the rpoB L430P mutation, conferring low-level RR, was identified in 32/230 (13.9%) RMR-TB versus 10/889 (1.1%) in MDR-TB (p<0.0001). Among 10 isolates with an rpoB L430P mutation, 7 were phenotypically susceptible using the critical concentration of 0.5 μg/ml (range 0.125-1 μg/ml). The majority (215/230, 93.5%) of RMR-TB isolates showed susceptibility to all other TB drugs, highlighting the potential benefits of WGS for simplified treatment. These data suggest that the evolution of RMR-TB differs from MDR-TB with a potential contribution from HIV infection.

scholarly journals Concurrent evaluation of microscopic observation of drug susceptibility assay for pulmonary and extrapulmonary tuberculosis

2017 ◽  
Vol 9 (02) ◽  
pp. 089-094
Author(s):  
Sonali Sudhir Zadbuke ◽  
Reena Set ◽  
Nishat Khan ◽  
Jayanthi Shastri
Keyword(s):  
Microscopic Observation ◽  
Extrapulmonary Tuberculosis ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Solid Media ◽  
Mdr Tb ◽  
Lowenstein Jensen ◽  
Proportion Method ◽  
Time To Detection

Abstract BACKGROUND: Methods for detection and drug susceptibility of tuberculosis (TB) with solid media are inexpensive but slow and laborious. Rapid methods to diagnose TB and multidrug-resistant TB (MDR-TB) are a global priority for TB control. OBJECTIVES: A study was performed to compare the sensitivity of detection of mycobacterial growth and time of culture positivity by microscopic observation of drug susceptibility (MODS) assay with that of Lowenstein–Jensen (LJ) culture in pulmonary and extrapulmonary TB and to evaluate the concordance of the susceptibilities to isoniazid (INH) and rifampicin (RIF) by MODS and proportion method on LJ. MATERIALS AND METHODS: A prospective, laboratory-based study was conducted on a total of 300 samples from suspected cases of pulmonary and extrapulmonary TB. Samples were inoculated on LJ medium as per the standard guidelines and MODS assay was performed. RESULTS: Sensitivity of MODS assay was 80% and 83.3% and specificity was 92.9% and 83.3% for pulmonary and extrapulmonary samples, respectively. Difference between mean time to detection of Mycobacterium TB (MTB) by LJ medium and MODS was statistically significant, with MODS being faster. drug susceptibility testing (DST) by MODS when compared to economic variant of proportion method was 87.87% for RIF, 90.9% for INH, and 96.96% for MDR-TB detection. CONCLUSIONS: MODS assay provides rapid, safe, and sensitive detection of TB faster than the existing gold standard. It is extremely promising in effectively diagnosing MDR-TB.

Seasonal dynamics of tuberculosis epidemics and implications for multidrug-resistant infection risk assessment

2013 ◽  
Vol 142 (2) ◽  
pp. 358-370 ◽  
Author(s):  
Y.-J. LIN ◽  
C.-M. LIAO
Keyword(s):  
Seasonal Dynamics ◽  
Multidrug Resistant ◽  
Infection Risk ◽  
Assessment Model ◽  
Relative Fitness ◽  
Tropical Regions ◽  
Resistant Infection ◽  
Control Programmes ◽  
Mdr Tb ◽  
The Impact

SUMMARYUnderstanding how seasonality shapes the dynamics of tuberculosis (TB) is essential in determining risks of transmission and drug resistance in (sub)tropical regions. We developed a relative fitness-based multidrug-resistant (MDR) TB model incorporated with seasonality and a probabilistic assessment model to assess infection risk in Taiwan regions. The model accurately captures the seasonal transmission and population dynamics of TB incidence during 2006–2008 and MDR TB in high TB burden areas during 2006–2010 in Taiwan. There is ∼3% probability of having exceeded 50% of the population infected attributed to MDR TB. Our model not only provides insight into the understanding of the interactions between seasonal dynamics of TB and environmental factors but is also capable of predicting the seasonal patterns of TB incidence associated with MDR TB infection risk. A better understanding of the mechanisms of TB seasonality will be critical in predicting the impact of public control programmes.

scholarly journals Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anwar Sheed Khan ◽  
Jody E. Phelan ◽  
Muhammad Tahir Khan ◽  
Sajid Ali ◽  
Muhammad Qasim ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Gene Mutations ◽  
Multidrug Resistant ◽  
Rifampicin Resistance ◽  
Resistance Mutations ◽  
Khyber Pakhtunkhwa ◽  
Tb Control ◽  
Mdr Tb ◽  
Compensatory Mutations

AbstractTuberculosis (TB), caused by Mycobacterium tuberculosis, is endemic in Pakistan. Resistance to both firstline rifampicin and isoniazid drugs (multidrug-resistant TB; MDR-TB) is hampering disease control. Rifampicin resistance is attributed to rpoB gene mutations, but rpoA and rpoC loci may also be involved. To characterise underlying rifampicin resistance mutations in the TB endemic province of Khyber Pakhtunkhwa, we sequenced 51 M. tuberculosis isolates collected between 2016 and 2019; predominantly, MDR-TB (n = 44; 86.3%) and lineage 3 (n = 30, 58.8%) strains. We found that known mutations in rpoB (e.g. S405L), katG (e.g. S315T), or inhA promoter loci explain the MDR-TB. There were 24 unique mutations in rpoA, rpoB, and rpoC genes, including four previously unreported. Five instances of within-host resistance diversity were observed, where two were a mixture of MDR-TB strains containing mutations in rpoB, katG, and the inhA promoter region, as well as compensatory mutations in rpoC. Heteroresistance was observed in two isolates with a single lineage. Such complexity may reflect the high transmission nature of the Khyber Pakhtunkhwa setting. Our study reinforces the need to apply sequencing approaches to capture the full-extent of MDR-TB genetic diversity, to understand transmission, and to inform TB control activities in the highly endemic setting of Pakistan.

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