scholarly journals Epidemiology of Antituberculosis Drug Resistance in Saudi Arabia: Findings of the First National Survey

2013 ◽  
Vol 57 (5) ◽  
pp. 2161-2166 ◽  
Author(s):  
Sahal Al-Hajoj ◽  
Bright Varghese ◽  
Mohammed M. Shoukri ◽  
Ruba Al-Omari ◽  
Mais Al-Herbwai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Saudi Arabia ◽  
National Survey ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Control Measures ◽  
Foreign Born ◽  
Primary Drug Resistance ◽  
Mdr Tb

ABSTRACTThe real magnitude of antituberculosis (anti-TB) drug resistance in Saudi Arabia is still unknown because the available data are based on retrospective laboratory studies that were limited to hospitals or cities. A representative national survey was therefore conducted to investigate the levels and patterns of anti-TB drug resistance and explore risk factors. Between August 2009 and July 2010, all culture-positive TB patients diagnosed in any of the tuberculosis reference laboratories of the country were enrolled. Isolates obtained from each patient were tested for susceptibility to first-line anti-TB drugs by the automated Bactec MGIT 960 method. Of the 2,235 patients enrolled, 75 cases (3.4%) were lost due to culture contamination and 256 (11.5%) yielded nontuberculous mycobacteria (NTM). Finally, 1,904 patients (85.2% of those enrolled) had available drug susceptibility testing results. Monoresistance to streptomycin (8.1%; 95% confidence interval [CI], 7.2 to 9.1), isoniazid (5.4%; 95% CI, 4.7 to 6.2), rifampin (1%; 95% CI, 0.7 to 1.3) and ethambutol (0.8%; 95% CI, 0.5 to 1.2) were observed. Multidrug-resistant TB (MDR-TB) was found in 1.8% (95% CI, 1.4 to 2.4) and 15.9% (95% CI, 15.4 to 16.5) of new and previously treated TB cases, respectively. A treatment history of active TB, being foreign-born, having pulmonary TB, and living in the Western part of the country were the strongest independent predictors of MDR-TB. Results from the first representative national anti-TB drug resistance survey in Saudi Arabia suggest that the proportion of MDR-TB is relatively low, though there is a higher primary drug resistance. A strengthened continuous surveillance system to monitor trends over time and second-line anti-TB drug resistance as well as implementation of innovative control measures, particularly among immigrants, is warranted.

scholarly journals Diagnostic Value of GeneChip for Detection of Resistant Mycobacterium tuberculosis in Patients with Differing Treatment Histories

2014 ◽  
Vol 53 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Limei Zhu ◽  
Qiao Liu ◽  
Leonardo Martinez ◽  
Jinyan Shi ◽  
Cheng Chen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Diagnostic Value ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Standard Drug ◽  
Related Data ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Previously Treated

The increasing burden of drug-resistant tuberculosis (TB) poses an escalating threat to national TB control programs. To assist appropriate treatment for TB patients, accurate and rapid detection of drug resistance is critical. The GeneChip test is a novel molecular tool for the diagnosis of TB drug resistance. Performance-related data on GeneChip are limited, and evaluation in new and previously treated TB cases has never been performed. We evaluated the diagnostic performance of GeneChip in detecting resistance to rifampin (RMP) and isoniazid (INH) and in detecting multidrug-resistant tuberculosis (MDR-TB) in comparison with standard drug susceptibility testing (DST) and compared the results in a group of previously treated and newly detected TB patients in an urban area in southeastern China. One thousand one hundred seventy-three (83.8%) new cases and 227 (16.2%) previously treated cases were collected between January 2011 and September 2013. The GeneChip showed a specificity of 97.8% and a sensitivity of 94.8% for detection of RMP resistance and 97.3% and 70.9%, respectively, for INH resistance in new cases. For previously treated cases, the overall sensitivity, specificity, and agreement rate are 94.6%, 91.3%, and 92.1%, respectively, for detection of RMP resistance and 69.7%, 95.4%, and 86.8%, respectively, for INH resistance. The sensitivity and specificity of MDR-TB were 81.8% and 99.0% in new cases and 77.8% and 93.4% in previously treated cases, respectively. The GeneChip system provides a simple, rapid, reliable, and accurate clinical assay for the detection of TB drug resistance, and it is a potentially important diagnostic tool in a high-prevalence area.

scholarly journals Transmission patterns of rifampicin resistant Mycobacterium tuberculosis complex strains in Cameroon: a genomic epidemiological study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Matthias Merker ◽  
Nkongho F. Egbe ◽  
Yannick R. Ngangue ◽  
Comfort Vuchas ◽  
Thomas A. Kohl ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Prolonged Exposure ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
High Dose ◽  
Factors Affecting ◽  
Recent Transmission ◽  
Mdr Tb

Abstract Background Determining factors affecting the transmission of rifampicin (RR) and multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains under standardized tuberculosis (TB) treatment is key to control TB and prevent the evolution of drug resistance. Methods We combined bacterial whole genome sequencing (WGS) and epidemiological investigations for 37% (n = 195) of all RR/MDR-TB patients in Cameroon (2012–2015) to identify factors associated with recent transmission. Results Patients infected with a strain resistant to high-dose isoniazid, and ethambutol had 7.4 (95% CI 2.6–21.4), and 2.4 (95% CI 1.2–4.8) times increased odds of being in a WGS-cluster, a surrogate for recent transmission. Furthermore, age between 30 and 50 was positively correlated with recent transmission (adjusted OR 3.8, 95% CI 1.3–11.4). We found high drug-resistance proportions against three drugs used in the short standardized MDR-TB regimen in Cameroon, i.e. high-dose isoniazid (77.4%), ethambutol (56.9%), and pyrazinamide (43.1%). Virtually all strains were susceptible to fluoroquinolones, kanamycin, and clofazimine, and treatment outcomes were mostly favourable (87.5%). Conclusion Pre-existing resistance to high-dose isoniazid, and ethambutol is associated with recent transmission of RR/MDR strains in our study. A possible contributing factor for this observation is the absence of universal drug susceptibility testing in Cameroon, likely resulting in prolonged exposure of new RR/MDR-TB patients to sub-optimal or failing first-line drug regimens.

scholarly journals Comparative Utility of Genetic Determinants of Drug Resistance and Phenotypic Drug Susceptibility Profiling in Predicting Clinical Outcomes in Patients With Multidrug-Resistant Mycobacterium tuberculosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Yang Che ◽  
Tianchi Yang ◽  
Lv Lin ◽  
Yue Xiao ◽  
Feng Jiang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Latent Class ◽  
Treatment Success ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Sputum Smear ◽  
Genetic Determinants ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Setting: Programmatic management of drug-resistant tuberculosis in Ningbo, China.Objective: To assess whether data-driven genetic determinants of drug resistance patterns could outperform phenotypic drug susceptibility testing in predicting clinical meaningful outcomes among patients with multidrug-resistant tuberculosis (MDR-TB).Design: We conducted a prospective cohort study of 104 MDR-TB patients. All MDR-TB isolates underwent drug susceptibility testing and genotyping for mutations that could cause drug resistance. Study outcomes were time to sputum smear conversion and probability of treatment success, as well as time to culture conversion within 6 months. Data were analyzed using latent class analysis, Kaplan–Meier curves, and Cox regression models.Results: We report that latent class analysis of data identified two latent classes that predicted sputum smear conversion with P = 0.001 and area under receiver-operating characteristic curve of 0.73. The predicted latent class memberships were associated with superior capability in predicting sputum culture conversion at 6 months and overall treatment success compared to phenotypic drug susceptibility profiling using boosted logistic regression models.Conclusion: These results suggest that genetic determinants of drug resistance in combination with phenotypic drug-resistant tests could serve as useful biomarkers in predicting treatment prognosis in MDR-TB.

scholarly journals Primary drug resistance in a region with high burden of tuberculosis. A critical problem

2015 ◽  
Vol 57 (2) ◽  
pp. 177 ◽  
Author(s):  
Cecilia Villa-Rosas ◽  
Rafael Laniado-Laborín ◽  
Lorena Oceguera-Palao
Keyword(s):  
Drug Resistance ◽  
Negative Impact ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
High Burden ◽  
Resistant Tuberculosis ◽  
Primary Drug Resistance ◽  
Very High ◽  
Line Drug

Objective. To determine rates of drug resistance in new cases of pulmonary tuberculosis in a region with a high burden of the disease. Materials and methods. New case suspects were referred for drug susceptibility testing. Results. 28.9% of new cases were resistant to at least one first line drug; 3.9% had a multidrug-resistant strain, 15.6% a monoresistant strain and 9.4% a polyresistant strain. Conclusion.Our rate of drug resistant tuberculosis in new cases is very high; this has important clinical implications, since even monoresistance can have a negative impact on the outcome of new cases treated empirically with a six month regimen.

scholarly journals Prevalence of Multi-Drug Resistant Mycobacterium Tuberculosis in Khyber Pakhtunkhwa – A High Tuberculosis Endemic Area of Pakistan

2020 ◽  
Vol 69 (2) ◽  
pp. 133-137 ◽  
Author(s):  
SAJID ALI ◽  
MUHAMMAD TAHIR KHAN ◽  
ANWAR SHEED KHAN ◽  
NOOR MOHAMMAD ◽  
MUHAMMAD MUMTAZ KHAN ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Large Scale ◽  
Simple Random Sampling ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Khyber Pakhtunkhwa ◽  
Mdr Tb

Anti-tuberculosis therapy involves the combination of drugs to hamper the growth of Mycobacterium tuberculosis (MTB). The emergence of multidrug-resistant tuberculosis (MDR-TB) is a global concern. Pakistan has been ranked 5th position in terms of a high burden of MDR-TB in the world. The aim of the current study was to investigate the prevalence of drug resistance in MTB in Khyber Pakhtunkhwa. Random samples were collected from 25 districts using the simple random sampling formula. All samples were processed in a biosafety level 3 laboratory for culture and drug susceptibility testing. Among 5759 presumptive tuberculosis (TB) cases, 1969 (34%) were positive. The proportion of TB was higher in females (39%) than males (29%), thus it represents a significant association between gender and tuberculosis (p < 0.05). People ages between 25 to 34 years were more likely to be infected with MTB (40%). Drug-resistant profile showed 97 (4.9%) patients were infected with MDR-TB. Streptomycin resistance was the highest and was observed in 173 (9%) isolates followed by isoniazid in 119 (6%) isolates. The lowest resistance was observed to pyrazinamide (3%). The prevalence of MDR-TB (10.4%) among patients that previously received anti-tuberculosis treatment is seemingly high. A large-scale drug resistance survey is required to evaluate the drug resistance for better management of tuberculosis.

scholarly journals Rapid Molecular Diagnosis of Tuberculosis and Its Resistance to Rifampicin and Isoniazid with Automated MDR/MTB ELITe MGB® Assay

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 797
Author(s):  
Vichita Ok ◽  
Alexandra Aubry ◽  
Florence Morel ◽  
Isabelle Bonnet ◽  
Jérôme Robert ◽  
...  
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Clinical Samples ◽  
Great Promise ◽  
Routine Practice ◽  
Pcr Assay ◽  
Perfect Agreement ◽  
Mdr Tb ◽  
Good Agreement

The MDR/MTB ELITe MGB® kit (ELITech) carried on the ELITe InGenius® platform is a new real-time PCR assay allowing automated extraction and detection of DNA of the Mycobacterium tuberculosis complex (MTB) and mutations in the rpoB and katG genes and inhA promoter region (pro-inhA) associated to resistance to rifampicin and isoniazid, the two markers of multidrug-resistant TB (MDR). We assessed the performances of the test on a collection of strains (n = 54) and a set of clinical samples (n = 242) from routine practice, comparatively to TB diagnosis and genotypic drug susceptibility testing (gDST) as references. Regarding the 242 clinical samples, the sensitivity and specificity of MTB detection by ELITe were 90.9% and 97.5%, respectively. For the detection of resistance-conferring mutations on positive clinical samples, we observed perfect agreement with gDST for katG and pro-inhA (κ = 1.0) and two discordant results for rpoB (κ = 0.82). Considering the 54 cultured strains, very good agreement with gDST was observed for the detection of the 25 distinct mutations in rpoB, katG, and pro-inhA, (κ = 0.95, 0.88, and 0.95, respectively). In conclusion, the automated MDR/MTB ELITe MGB® assay shows great promise and appears to be a valuable tool for rapid detection of pre-MDR- and MDR-TB directly from clinical specimens.

scholarly journals Cost of illness of non-multidrug-resistant tuberculosis in Germany: an update

2020 ◽  
Vol 6 (4) ◽  
pp. 00329-2020
Author(s):  
Roland Diel ◽  
Albert Nienhaus
Keyword(s):  
Central Committee ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Current Therapy ◽  
Productivity Losses ◽  
Public Health Screening ◽  
Mdr Tb ◽  
The Mean ◽  
Mean Cost

BackgroundA total of 5429 new cases of tuberculosis (TB) were reported in Germany in 2018; out of the 3780 TB cases for whom drug susceptibility testing was available, the proportion of multidrug-resistant TB (MDR-TB) cases was only 3.1% (118 cases).MethodsOn the basis of the current therapy guidelines of the German Central Committee against Tuberculosis, this study estimates the mean direct outpatient and combined in- and outpatient costs per non-MDR-TB patient from the perspective of the German statutory health insurance (SHI) system, together with costs arising from productivity losses and costs due to public health screening for TB in close contacts.ResultsFrom the insurance perspective, the mean outpatient costs (rounded) per case were €1628 for adults and €1179 for children for standard therapy; the mean cost of inpatient treatment amounted to €8626. The mean combined inpatient/outpatient cost was €8756 for adults and €8512 for children. As 95% of all TB patients were adults, the weighted treatment cost per patient in Germany in 2018 was €8746. These are in addition to the mean cost arising from productivity losses (€1839) and, weighted by pulmonary infectivity, cost of contact investigations (€368), coming to a total of €10 953.ConclusionGiven the clear increase in the number of non-MDR-TB cases since 2015, TB is still a disease of significant economic impact in Germany.

scholarly journals Molecular characterisation of multidrug-resistantMycobacterium tuberculosisisolates from a high-burden tuberculosis state in Brazil

2019 ◽  
Vol 147 ◽  
Author(s):  
R. S. Salvato ◽  
S. Schiefelbein ◽  
R. B. Barcellos ◽  
B. M. Praetzel ◽  
I. S. Anusca ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Molecular Characterisation ◽  
Drug Resistant ◽  
Isoniazid Resistance ◽  
High Burden ◽  
Brics Countries ◽  
Mdr Tb

AbstractTuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131Mycobacterium tuberculosis (M.tb)DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of thekatG,inhA andrpoB genes and RDRiosublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRiodeletion was observed in 42 (32%) of theM.tbisolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%)M.tbisolates, we found mutations associated with rifampicin (RIF) resistance inrpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance inkatG andinhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in therpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

A Rapid and Accurate Detection Approach for Multidrug-Resistant Tuberculosis Based on PCR-ELISA Microplate Hybridization Assay

2020 ◽  
Vol 51 (6) ◽  
pp. 606-613
Author(s):  
Ye-Cheng Zhou ◽  
Shu-Mei He ◽  
Zi-Lu Wen ◽  
Jun-Wei Zhao ◽  
Yan-Zheng Song ◽  
...  
Keyword(s):  
Clinical Care ◽  
Pcr Amplification ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Hybridization Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

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.

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 ◽  
...  
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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