TUBERCULOSIS: Resistant TB from inappropriate treatment

 November 22, 2011 Results of a systematic review and meta-analysis lend further weight to the role of inappropriate treatment in the rise of multidrug resistant tuberculosis (MDR-TB).
The Dutch and Swedish research team acknowledges it's generally accepted that inadequate treatment leads to resistance – but this group of researchers wanted even more evidence.
As reported online in the European Respiratory Journal, when Dr Marieke J. van der Werf of the KNCV Tuberculosis Foundation at The Hague and colleagues reviewed the literature, they found little information regarding treatment regimens, drug-resistance profile before treatment and at failure or recurrence, and genotype information at failure or recurrence.
The diagnosis of acquired MDR-TB required that the patient initially have a Mycobacterium tuberculosis strain that was susceptible to at least isoniazid or rifampicin, which became MDR-TB at the time of failure or disease-recurrence and with a genotype pattern identical to the initial strain at time of first diagnosis.

Study review
The researchers eventually identified and reviewed four studies, ranging in size from 233 to 2,901 patients.
Only two trials met the criteria for meta-analysis inclusion, however; these two involved more than 3,200 patients and showed that the risk of developing MDR-TB is 27-fold increased in patients who are prescribed an inappropriate treatment regimen.
The researchers added, "We believe that the risk that patients defined as having acquired MDR-TB were in fact re-infected with an identical strain that already was MDR-TB, is small."
"The new review provides evidence for the general opinion that the development of MDR-TB can be caused by treatment that is inadequate," the authors conclude.
They say "the evidence is based on the best quality studies available" and "If more studies become available the review and meta-analysis can be updated."
http://www.health24.com/news/Tuberculosis/1-4011,71631.asp

June 1, 2011


Understanding     
tuberculosis drug resistance: super-drug inactivator revealed



ANN ARBOR, Mich.—Researchers at the University of Michigan's Life Sciences Institute and College of Pharmacy have uncovered how tuberculosis builds drug resistance.
The discovery could provide scientists with a new direction to try to combat drug-resistant tuberculosis and to head off the continued spread of this deadly infectious disease.
Tuberculosis claims about 2 million lives worldwide each year. With the global spread of the pathogenic bacterium that currently infects one-third of the world's population, there are also strains that are resistant to most types of antibiotics that are used to treat this infection.
These strains cause so-called multi-drug resistant tuberculosis and extensively drug resistant tuberculosis. The limited number of drugs that are used to treat these resilient infections are our last line of defense, and some bacteria have already evolved resistance even to these antibiotics. The family of aminoglycoside antibiotics is among these drugs.
Sylvie Garneau-Tsodikova, LSI research assistant professor and the John G. Searle Assistant Professor of Medicinal Chemistry, and collaborator Oleg Tsodikov, assistant professor of medicinal chemistry at the U-M College of Pharmacy, have uncovered a sophisticated and efficient mechanism that tuberculosis uses to inactivate aminoglycosides.
"Bacteria continuously come up with new tricks to inactivate the drugs that we develop and use to treat infections," said Garneau-Tsodikova. "As a result, our antibiotic arsenal becomes more and more limited. To overcome bacterial resistance, a deeper understanding of the many resistance mechanisms evolved by bacteria is needed."
The tuberculosis protein Eis destroys aminoglycoside antibiotics once they are inside of the microbe. In a collaborative effort, the Garneau-Tsodikova and Tsodikov labs discovered that Eis chemically changes (acetylates) the aminoglycoside drugs at many different places to ensure that they become completely inactive and lose their antibiotic activity. Amazingly, Eis inactivates most aminoglycosides that were tested, including all that are currently administered by doctors.
"It is always a humbling experience to realize the power of nature to combat the drugs that scientists develop," said Garneau-Tsodikova.
This Eis multi-acetylation inactivation mechanism is completely novel and represents one more challenge to keep in mind for the future development of treatments for tuberculosis.
The researchers are now using this knowledge to change drug scaffolds to minimize this effect and to try to overcome the resistance with new drugs against Eis, which would make aminoglycoside antibiotics active again.
The details of their findings on this super-drug inactivator in tuberculosis were reported in the May 31 issue of the journal Proceedings of the National Academy of Sciences. Graduate student Wenjing Chen (Garneau-Tsodikova lab) and research investigator Tapan Biswas (Tsodikov lab) are the main co-authors of this work.

The research was supported by the Life Sciences Institute and the U-M College of Pharmacy.
http://ns.umich.edu/htdocs/releases/story.php?id=8425

TUBERCULOSIS: Drug misuse leading to resistant strain of TB

P. Koshy , jacob.k@livemint.com

Drug misuse leading to resistant strain of TB
Proportion of improper dosage strengths in India was twice the average of the 10 nations surveyedJacob

A proliferation of tuberculosis drugs and a marked deviation from nationally mandated treatment plans may be a key cause of the increasing incidence of a highly resistant strain of tuberculosis in India, according to a study published in PLoS One, the peer-reviewed journal of the Public Library of Sciences.
“..At least a third of all private sector dosages of first-line TB drugs fall outside of national and international treatment recommendations. Any resulting drug misuse could be responsible for many treatment failures and for escalating the emergence of multidrug-resistant TB (MDR-TB), which is further worsening the TB epidemic.,” the researchers said in a press statement accompanying their publication.
The primary aim of the study was to ascertain the size of the private-sector drug supply market in 10 key developing countries which account for about 60% of the world’s tuberculosis patients.
The researchers found that India’s private TB drug market extended treatment to more than two million cases—more than all of the nine countries combined—and the proportion of improper dosage strengths in the country was twice the average of the 10 countries surveyed in the study.
For every 100 drugs required in the proper dosage to treat TB, there were 117 available—an oversupply that authors claim could play a role in fostering drug resistance. The researchers also found in a study of 100 physicians that nearly 80 different dosages and treatment plans were prescribed; internationally, there are only about 14 prescribed treatment combinations
To be sure, the study doesn’t draw a correlation between the extent of private sector participation in the TB drug market and the number of tuberculosis cases. Nor does it comment on whether public sector supply of TB drugs by government agencies ensures better recovery. The authors, most of whom are based in the United States, couldn’t be immediately contacted for an explanation.
TB is one of the leading causes of morbidity and mortality worldwide and claims around 1.7 million lives annually. One in five of these victims are found in India, which also harbours the highest number of TB patients globally. According to WHO, there were 440,000 cases of multidrug-resistant TB in the world in 2008; and at least a third of the MDR-TB patients who were able to access MDR-TB treatment still died. Figures for India aren’t available.
One reason why TB continues to reign in many parts of the world is the old and inadequate treatment for the disease. There have been no new TB drugs for nearly 50 years and current regimens take between six and nine months — too long and complex. As a result, many patients do not complete their drug regimen, which leads to drug resistance, an emerging global health threat. The treatment for drug-resistant TB can take two years or longer, involve multiple drugs and injectables, and is much more expensive than the first-level of treatment.
The research, which involved analysing questionnaires filled out by physicians and scrutinizing drug-sale databases, was conducted by the TB Alliance—a non-profit— and IMS Health (a healthcare market research and consulting-services firm), and is the first detailed study of the private TB drug market across multiple high-burden countries.
The Bill and Melinda Gates Foundation as well as the governments of the United Kingdom and the Netherlands are among those that funded the study.
Nearly equal amounts of TB drugs are dispensed in the public and private sectors (enough to treat 67% vs. 66% of estimated incidence, respectively) according to the study and though the size of the private sector market for TB drugs varies between countries, it has been steady within most countries over the past five years.
The authors say the study emphasizes that greater efforts ought to be made to co-opt the private sector in battling tuberculosis. “The private sector is keeping alive the confusion that existed previously in the public sector,” said Dr William Wells, the study’s lead author and director of Market Access at the TB Alliance, in a statement. “With this new baseline understanding of the TB drug market, we can no longer ignore the private sector’s critical role in the access equation for TB treatment and in the task of protecting both current drugs and new regimens from the development of resistance.”
“Most countries covered in this study have public-private mix (PPM) programmes for TB care,” said Mario Raviglione, Director of the Stop TB Department at WHO. “Based on country experiences, these programmes have shown good results in optimizing TB management by private care providers. But the size of the response is not commensurate with the size of the challenge; there is enormous scope to expand these programmes urgently. Private providers following best practices should be supported through accreditation and access to free TB drugs from the public sector, while those not doing so should be regulated.”
V. N. Singh, a tuberculosis expert at the All India Institute of Medical Sciences said the results of the study weren’t surprising because of India’s extremely poor network of public health care. “It isn’t easy for all patients to immediately access public health centres. That’s true across ailments and diseases and not TB alone. That said a significant majority of TB drugs, over 60%, is still available only via government channels.”
http://www.livemint.com/2011/05/05222638/Drug-misuse-leading-to-resista.html?atype=tp

TUBERCULOSIS: Sequencing Study Finds Mutations in Latent Tuberculosis Bugs

April 25, 2011   By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – An online study in Nature Genetics yesterday hints that drug resistance may arise in tuberculosis-causing bacteria even during latent stages of infection.
A Harvard University-led team sequenced the genomes of nearly three-dozen Mycobacterium tuberculosis isolates collected from nine infected macaques. When they used SNP data to gauge mutation rates at different stages of infection, the researchers found comparable levels of mutation under each of the conditions tested. The findings suggest drug resistance — including resistance to a treatment that relies on the antibiotic isoniazid alone — can likely occur even when tuberculosis infection is not at an active stage.
"We show that [M. tuberculosis] continues to acquire mutations during disease latency," senior author Sarah Fortune, an immunology and infectious diseases researcher with the Harvard School of Public Health, and her co-authors wrote, "which may explain why isoniazid monotherapy for latent tuberculosis is a risk factor for the emergence of isoniazid resistance."
Active tuberculosis is typically tackled with a combination of different antibiotics, the researchers explained. Latent infections, on the other hand, are considered less mutation prone, and are more often treated with a lone antibiotic called isoniazid, or INH.
Nevertheless, some epidemiological studies have reported elevated INH resistance in tuberculosis-causing bugs that had been treated with this preventative monotherapy, the authors explained, raising suspicions that mutations may be more common during latency than previously appreciated — a possibility that the team explored with whole-genome sequencing.
"[W]e sought to define the mutational capacity of the bacterium during infection to better predict the rate at which drug resistance can be expected to emerge in active, latent, and reactivated disease," they wrote.
Using the Illumina Genome Analyzer, the researchers did single-read and paired-end sequencing of a M. tuberculosis strain known as Erdman and of 33 M. tuberculosis isolates from nine macaques that either had active tuberculosis infections, latent infections, or infections that were re-activated after a period of latency.
In the process, they generated sequence that covered 93 percent of each genome, on average, to a depth of about 117 times.
After tracking down variants in the genomes and verifying them with targeted Sanger sequencing, the team was left with 14 SNPs that seem to have arisen over the course of macaque infections. But rather than seeing more mutations in the isolates from macaques with active tuberculosis infections, the researchers found comparable mutation rates in each of the three infection scenarios.
"Our data indicate that in macaques with active, latent, and reactivated disease, the bacterial populations acquire mutations at the same rate over time, regardless of the number of bacterial replications that have occurred," they wrote.
Moreover, their subsequent experiments hint that these mutation rates are similar to those found when M. tuberculosis is grown in a lab setting.
The findings suggest that drug resistance is not only an issue to contend with during active tuberculosis infection, the researchers explained, since bacteria can also mutate during latent infection and in early stages of reactivation.
Those involved in the study emphasize that more research is needed to understand whether M. tuberculosis mutation patterns are similar in infected humans. Still, they say, the results underscore the need for surveillance for resistance-related mutations — particularly if preventative INH treatment becomes more broadly used to treat latent tuberculosis in some populations, including those infected with HIV.
"[INH preventative monotherapy] is now being recommended globally for HIV-positive individuals with latent tuberculosis where bacterial burden and the rate of treatment failure may be higher because of immunocompromise," the authors noted.
"If our data from the macaque model are predictive of the mutational capacity of [M. tuberculosis] in HIV-positive individuals, INH mono-resistance could arise at a substantial rate," they added. "These findings emphasize the importance of drug resistance testing and careful monitoring for treatment in these populations."
http://www.genomeweb.com/sequencing/sequencing-study-finds-mutations-latent-tuberculosis-bugs

New Test Effective for Detection of Tuberculosis

April 19, 2011.

Test for Mycobacterium tuberculosis, rifampicin resistance shows high sensitivity and specificity
Diagnosis of Mycobacterium tuberculosis (MTB) and rifampicin resistance (RIF), detected by the MTB/RIF test, is accurate and feasible in resource-poor countries, according to a study published online April 19 in The Lancet.
 Diagnosis of Mycobacterium tuberculosis (MTB) and rifampicin resistance (RIF), detected by the MTB/RIF test, is accurate and feasible in resource-poor countries, according to a study published online April 19 in The Lancet.
Catharina C. Boehme, M.D., from the Foundation for Innovative New Diagnostics in Geneva, Switzerland, and colleagues evaluated whether the Xpert MTB/RIF test was feasible, robust, and accurate. Between 2009 and 2010, sputum smears and cultures of 6,648 tuberculosis patients were collected, and one-off direct MTB-RIF testing was compared to other detection methods. Indicators of robustness included indeterminate rate and between-site performance. The time to detection, reporting, treatment, and patient dropouts were compared between different tuberculosis-detection techniques.
The investigators found that one-off MTB/RIF testing detected 90.3 percent of 1,033 culture-confirmed tuberculosis cases, and microscopy detected 67.1 percent of 1,041 cases. The MTB/RIF test was 76.9 percent sensitive and 99.0 percent specific for smear-negative, culture-positive patients. Test sensitivity was 94.4 percent and specificity was 98.3 percent for rifampicin resistance. In contrast to microscopy, test sensitivity did not decrease significantly in patients with HIV co-infection. Average tuberculosis detection time was zero days for MTB/RIF, one day for microscopy, and 30 and 16 days for solid and liquid cultures, respectively. Average resistance detection time was 20 and 106 days for line-probe assay and conventional drug-susceptibility test, respectively. The MTB/RIF test reduced the average treatment time from 56 to five days for smear-negative tuberculosis. The indeterminate rate was 2.4 and 4.6 percent for MTB/RIF and cultures, respectively.
"Our findings suggest that decentralized MTB/RIF test implementation is feasible and could lead to an improvement in tuberculosis care and control," the authors write.
Several study authors disclosed financial relationships with Cepheid, which developed the MTB/RIF test and partially funded the study.
http://www.doctorslounge.com/index.php/news/pb/19477

TUBERCULOSIS: Genetic variation of Mycobacterium tuberculosis circulating in Kharkiv Oblast, Ukraine.

Maya A Dymova , Oleksandr A Liashenko , Petro I Poteiko , Valeriy S Krutko , Evgenyi A Khrapov and Maxim L Filipenko BMC Infectious Diseases 2011, 11: 28 March 2011

Background
A persistent increase of tuberculosis cases has recently been noted in the Ukraine. The reported incidence of drug-resistant isolates of M. tuberculosis is growing steadily; however, data on the genetic variation of isolates of M. tuberculosis circulating in northern Ukraine and on the spectrum and frequency of occurrence of mutations determining resistance to the principal anti-tuberculosis drugs isoniazid and rifampicin have not yet been reported.

Methods
Isolates of M. tuberculosis from 98 tuberculosis patients living in Kharkov Region (Ukraine) were analyzed using VNTR- and RFLP-IS6110-typing methods. Mutations associated with resistance to rifampicin and isoniazid were detected by RFLP-PCR methods, and also confirmed by sequencing.

Results
We identified 75 different genetic profiles. Thirty four (34%) isolates belonged to the Beijing genotype and 23 (23%) isolates belonged to the LAM families. A cluster of isolates belonging to the LAM family had significant genetic heterogeneity, indicating that this family had an ancient distribution and circulation in this geographical region. Moreover, we found a significant percentage of the isolates (36%) belonged to as yet unidentified families of M. tuberculosis or had individual non-clustering genotypes. Mutations conferring rifampicin and isoniazid resistance were detected in 49% and 54% isolates, respectively. Mutations in codon 531 of the rpoB gene and codon 315 of the katG gene were predominant among drug-resisitant isolates. An association was found for belonging to the LAM strain family and having multiple drug resistance (R = 0.27, p = 0.0059) and also for the presence of a mutation in codon 531 of the rpoB gene and belonging to the Beijing strain family (R = 0.2, p = 0.04).

Conclusions
Transmission of drug-resistant isolates seems to contribute to the spread of resistant TB in this oblast. The Beijing genotype and LAM genotype should be seen as a major cause of drug -resistance TB in this region.
http://www.biomedcentral.com/1471-2334/11/77

TUBERCULOSIS: Book: Drug-Resistant Tuberculosis: Causes, Diagnosis and Treatments

Drug-Resistant Tuberculosis: Causes, Diagnosis and Treatments $129.00






Editors: Shui Ngụy and Zhou K'ung

Book Description:

Tuberculosis (TB) is a major public health problem of global proportions. It is the second leading cause of death from an infectious agent, killing nearly two million people each year, mostly in developing countries. This book outlines the recent advances in the development of new multidrug-resistant tuberculosis (MDR-TB) drugs. The emergence of resistance to antituberculosis drugs, particularly of MDR-TB and newly XDR-TB has become a major health problem. This book provides some glimpses into the current drugs including their mechanism of action, side-effects and mechanism of resistance. The desirable features of new drugs is also discussed, as well as different targets for effective TB treatment and approaches that are being made in the development of potential drugs for resistant tuberculosis. The effectiveness of levofloxacin and olfoxacin in the treatment of multi-drug resistant tuberculosis is also comparatively assessed to determine the immunological effects of certain treatment regimens. Finally, this book expands upon the spectrum of potential resistance-related mutations in MTB clinical isolates to help consolidate the framework for the development of molecular methods for delineating the drug susceptibility profiles in clinical laboratories.

Table of Contents:
Preface
Chapter I. Drug-Resistant Tuberculosis: Causes, Diagnosis and Treatment, pp. 1-58
(Suhail Ahmad, Eiman Mokaddas, Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait)
Chapter II. Tuberculosis – The Development of New MDR-TB Drugs , pp. 59-141
(Jarmila Vinšová, Martin Krátký, Faculty of Pharmacy, Charles University, Czech Republic)
Chapter III. Recent Advances towards the Development of New Drugs for Resistant Tuberculosis , pp. 143-176
(Ahmed Kamal, Shaik Azeeza, M. Shaheer Malik, Chemical Biology Laboratory, Division of Organic Chemistry, Indian Institute of Chemical Technology, India)
Chapter IV. Molecular Basis of Ethambutol Resistance in Mycobacterium Tuberculosis: Current Insights , pp. 177-200
(Igor Mokrousov, Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute, Russia)
Chapter V. Drug Resistant Tuberculosis in Bulgaria: Molecular Insights, pp. 201-223
(Violeta Valcheva, Nadya Markova, Nalin Rastogi, Olga Narvskaya, Igor Mokrousov, Department of Pathogenic Bacteria, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria, and others)
Chapter VI. Administration of TB Drugs in Resistance Cases Based on Bacterial Gene Expression Profiling , pp. 225-236
(Li M. Fu, Pacific Tuberculosis and Cancer Research Organization, Irvine, CA)
Chapter VII. A Prospective Assessment of Therapeutic Efficacy and Immune Effects of Levofloxacin and Ofloxacin in Multiple-Drug Resistant Tuberculosis, pp. 237-249
(Philip Martin Clark, Sule Apikoglu-Rabus, Bayram Kiran, Turan Karagoz, Fikret Vehbi Izzettin, Yeditepe University Department of Pharmacy, Istanbul, Turkey, and others)
Chapter VIII. Clinical and Pathomorphological Aspects of Tuberculosis in Hungary, pp. 251-262
(Losonczy György; Törõ Klára, Semmelweis University, Pulmonologal Clinic, Semmelweis University, Department of Forensic and Insurance Medicine)
Chapter IX. Management of Multi-Drug-Resistant Tuberculosis – Back to the Future? , pp. 263-273
(Wing-Wai Yew, Chen-Yuan Chiang, Tuberculosis and Chest Unit, Grantham Hospital, Hong Kong, China, and others)
Chapter X. Genetic and Phenotypic Characterization of Drug-Resistant Mycobacterium Tuberculosis Isolates , pp. 275-285
(Maysaa El Sayed Zaki, Professor of Clinical Pathology, Faculty of Medicine, Mansoura University, Egypt)
Chapter XI. Tuberculosis Treatment Failure: Causes and Solutions, pp. 287-307
(Philip Martin Clark, Sule Apikoglu-Rabus, Yeditepe University Faculty of Pharmacy, Clinical Pharmacy Department, Istanbul, Turkey and others)

https://www.novapublishers.com/catalog/product_info.php?products_id=24082&osCsid=

Drug-resistant M. tuberculosis more likely in foreign-born patients with TB Meningitis

 February 9, 2011

Vinnard C. Emerg Infect Dis. 2011; doi:10.3201/eid1703.101715.

Patients with tuberculosis meningitis born outside of the US were more likely to be infected with an isoniazid-resistant strain of Mycobacterium tuberculosis when compared with US-born patients, according to new findings from a cross-sectional study.
Christopher Vinnard, MD, of the division of infectious diseases at the University of Pennsylvania School of Medicine, and colleagues pooled data on tuberculosis meningitis cases between 1993 and 2005 from the US National Tuberculosis Surveillance System and assessed patient characteristics associated with isoniazid resistance.
Patients with a previous diagnosis of TB or with multidrug-resistant disease were excluded from the study.
Of 1,649 patients with tuberculosis meningitis, 14% were infected with isolates resistant to isoniazid, rifampin, ethambutol, pyrazinamide, or streptomycin — 8% were infected with at least one isoniazid-resistant isolate. Isoniazid-resistance was uncommon in patients aged older than 64 years.
Foreign birth was the only characteristic independently associated with isoniazid-resistance on initial testing (OR=2.53; 95% CI, 1.66–3.88). Twenty of the 69 foreign-born patients with isoniazid-resistant disease resided in Mexico; seven of the nine countries with 2 or more cases of isoniazid-resistant disease were located in Asia. Although 53% of patients were HIV-positive, no association was observed between HIV and isoniazid resistance (OR=1.10; 95% CI, 0.70-3.65).
“Prospective studies are needed to determine whether individual patient characteristics can guide the selection of tuberculosis meningitis therapies and lead to an improvement in clinical outcomes,” the researchers wrote.
http://infectiousdiseasenews.com/article/80361.aspx

TUBERCULOSIS: Epidemiology of Anti-tuberculosis Drug Resistance in a Chinese Population: Current Situation and Challenges Ahead

Epidemiology of Anti-tuberculosis Drug Resistance in a Chinese Population: Current Situation and Challenges Ahead
Yan Shao , Dandan Yang , Weiguo Xu , Wei Lu , Honghuan Song , Yaoyao Dai , Hongbing Shen and Jianming Wang
BMC Public Health 2011, 11:110doi:10.1186/1471-2458-11-110
17 February 2011

Background
Drug resistance has been a cause of concern for tuberculosis (TB) control in both developed and developing countries. Careful monitoring of the patterns and trends of drug resistance should remain a priority.

Methods
Strains were collected from 1824 diagnosed sputum smear positive pulmonary TB patients in Jiangsu province of China and then tested for drug susceptibility against rifampicin, isoniazid, ethambutol and streptomycin. The prevalence and patterns of drug resistance in mycobacterium tuberculosis (MTB) isolates were investigated. Multiple logistic regression analysis was performed to identify the risk factors for multidrug resistant (MDR) bacterial infection. The strength of association was estimated by odds ratio (OR) and 95% confidence interval (95% CI).

Results
The drug susceptibility tests showed that 1077(59.05%) MTB strains were sensitive to all the four antibiotics and the other 747(40.95%) strains were resistant to at least one drug. The proportions of mono-drug resistance were 28.73% for isoniazid, 19.41% for rifampicin, 29.33% for streptomycin, and 13.98% for ethambutol, respectively. The prevalence of MDR-TB was 16.61%, which was significantly different between new cases (7.63%) and those with previous treatment history (33.07%). Geographical variation of drug resistance was observed, where the proportion of MDR-TB among new cases was higher in the central (9.50%) or north part (9.57%) than that in the south area (4.91%) of Jiangsu province. The age of patients was significantly associated with the risk of drug resistance (P<0.001) and the adjusted OR (95% CI) was 1.88(1.26-2.81) for patients aged 35-44 years when compared with those 65 years or older. Patients with previous treatment history had a more than 5-fold increased risk of MDR-TB (adjusted OR: 6.14, 95% CI: 4.61-8.17), compared with those previously not having been treated.

Conclusions
The high prevalence of drug resistance has been a major challenge for TB control. Prevention and control of drug-resistant TB should be emphasized by the revised DOTS (direct observed therapy, short course) program through prompt case detection, routine and quality-assured drug susceptibility test for patients at high risk of resistance, programmatic treatment with both first and second-line medicines, and systematic treatment observation, with priority for high MDR-TB settings.

http://www.biomedcentral.com/1471-2458/11/110