Detection of multidrug-resistant Mycobacterium tuberculosis strains isolated in Brazil using a multimarker genetic assay for katG and rpoB genes (original) (raw)
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Expert Review of Anti-infective Therapy, 2007
Although progress has been made to reduce global incidence of drug-susceptible tuberculosis, the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis during the past decade threatens to undermine these advances. However, countries are responding far too slowly. Of the estimated 440 000 cases of MDR tuberculosis that occurred in 2008, only 7% were identifi ed and reported to WHO. Of these cases, only a fi fth were treated according to WHO standards. Although treatment of MDR and XDR tuberculosis is possible with currently available diagnostic techniques and drugs, the treatment course is substantially more costly and laborious than for drug-susceptible tuberculosis, with higher rates of treatment failure and mortality. Nonetheless, a few countries provide examples of how existing technologies can be used to reverse the epidemic of MDR tuberculosis within a decade. Major improvements in laboratory capacity, infection control, performance of tuberculosis control programmes, and treatment regimens for both drug-susceptible and drug-resistant disease will be needed, together with a massive scale-up in diagnosis and treatment of MDR and XDR tuberculosis to prevent drug-resistant strains from becoming the dominant form of tuberculosis. New diagnostic tests and drugs are likely to become available during the next few years and should accelerate control of MDR and XDR tuberculosis. Equally important, especially in the highest-burden countries of India, China, and Russia, will be a commitment to tuberculosis control including improvements in national policies and health systems that remove fi nancial barriers to treatment, encourage rational drug use, and create the infrastructure necessary to manage MDR tuberculosis on a national scale.
Tuberculosis Multidrug-resistant Tuberculosis – From Epidemiology to Treatment Design
European Respiratory & Pulmonary Diseases, 2015
Multidrug-resistant tuberculosis (MDR-TB) and extensively resistant tuberculosis (XDR-TB) are present in most regions of the world and represent a serious threat to the control of tuberculosis. They usually result from errors somewhere along the chain of management of the disease that favoured the selection of resistant mutants, progressively replacing drug-sensitive strains and transmitted to further patients. The currently recommended strategies for the control of this serious situation is the rapid identification of drug-resistant strains, careful drug management of patients with second-line drugs and prevention of the transmission of mycobacteria to contacts. Optimal selection and number of drugs and duration of treatment are not clearly defined. Prevention of the creation of additional cases of MDR-TB is crucial.
Multidrug-Resistant Mycobacterium tuberculosis: Molecular Perspectives
Emerging Infectious Diseases, 1998
Objective: To assess the determining factors for Mycobacterium tuberculosis multidrug resistance at a referral center for infectious diseases in the state of Minas Gerais, Brazil. Methods: A retrospective case-control study was conducted using data collected from September of 2000 to January of 2004. During this period, 473 cultures presenting growth of M. tuberculosis, corresponding to 313 patients, were submitted to susceptibility tests at the Central Laboratory of Minas Gerais. Cases presenting resistance to at least rifampin and isoniazid were classified as cases of multidrug resistance and were selected for study. These cases were paired to control group cases of drug-susceptible tuberculosis at a ratio of 1:3. Clinical and demographic data were analyzed using univariate and multivariate analyses. Results:
Multi-drug resistant tuberculosis burden and risk factors: An update
Kathmandu University Medical Journal, 1970
Multi-drug resistant (MDR) tuberculosis is defined as disease caused by Mycobacterium tuberculosis with resistance to at least two anti-tubercular drugs Isoniazid and Rifampicin. Recent surveillance data have revealed that prevalence of the drug resistant tuberculosis has risen to the highest rate ever recorded in the history. Drug resistant tuberculosis generally arises through the selection of mutated strains by inadequate therapy. The most powerful predictor of the presence of MDR-TB is a history of treatment of TB. Shortage of drugs has been one of the most common reasons for the inadequacy of the initial anti-TB regimen, especially in resource poor settings. Other major issues significantly contributing to the higher complexity of the treatment of MDR-TB is the increased cost of treatment. Other factors also play important role in the development of MDR-TB such as poor administrative control on purchase and distribution of the drugs with no proper mechanism on quality control a...
Journal of Infection and Public Health, 2014
The global burden of tuberculosis (TB) is still large. The increasing incidence of drug-resistant, multidrug-resistant (MDR) (resistant to at least rifampicin and isoniazid), and extensively drug-resistant (XDR) (additionally resistant to a fluoroquinolone and kanamycin/amikacin/capreomycin) strains of Mycobacterium tuberculosis and the association of active disease with human immunodeficiency virus coinfection pose a major threat to TB control efforts. The rapid detection of M. tuberculosis strains and drug susceptibility testing (DST) for anti-TB drugs ensure the provision of effective treatment. Rapid molecular diagnostic and DST methods have been developed recently. Treatment of drug-susceptible TB is effective in ≥95% of disease cases; however, supervised therapy for ≥6 months is challenging. Nonadherence to treatment often results in the evolution of drug-resistant strains of M. tuberculosis due to mutations in the genes encoding drug targets. Sequential accumulation of mutations results in the evolution of MDR and XDR strains of M. tuberculosis. Effective treatment of MDR-TB involves therapy with 5-7 less effective, expensive, and toxic second-line and third-line drugs for ≥24 months and is difficult in most developing countries. XDR-TB is generally an untreatable disease in developing countries. Some currently existing drugs and several new drugs with novel modes of action are in various stages of development to shorten the treatment duration of drug-susceptible TB and to improve the outcome of MDR-TB and XDR-TB.
Diagnostic Microbiology and Infectious Disease, 2015
This study correlates Minimum Inhibitory Concentrations (MICs) of rifampicin (RIF) and isoniazid (INH) with GenoType MTBDRplus assay results for drug-resistant Mycobacterium tuberculosis (MTB) clinical isolates. MICs of RIF and INH were established for 84 and 90 isolates, respectively, testing six concentrations of each drug. Genotypic resistance to each drug was determined by GenoType MTBDRplus assay with 50 representative mutations confirmed by pyrosequencing, with mutations in the rpoB gene associated with RIF-resistance and mutations in the katG and/or inhA genes associated with INH-resistance. Based upon the correlation of MICs with specific genetic profiles, relative resistance levels were established for each isolate. Results indicate that MTB phenotypic resistance, currently based upon the testing of isolate susceptibility to a single drug concentration, may be more accurately profiled via quantitative MICs, and therefore the correlation of molecular diagnostic results with specific MICs may allow for more optimal treatment of infections.
Multidrug-resistant tuberculosis around the world: what progress has been made?
The European respiratory journal, 2015
Multidrug-resistant tuberculosis (MDR-TB) (resistance to at least isoniazid and rifampicin) will influence the future of global TB control. 88% of estimated MDR-TB cases occur in middle- or high-income countries, and 60% occur in Brazil, China, India, the Russian Federation and South Africa. The World Health Organization collects country data annually to monitor the response to MDR-TB. Notification, treatment enrolment and outcome data were summarised for 30 countries, accounting for >90% of the estimated MDR-TB cases among notified TB cases worldwide. In 2012, a median of 14% (interquartile range 6-50%) of estimated MDR-TB cases were notified in the 30 countries studied. In 15 of the 30 countries, the number of patients treated for MDR-TB in 2012 (71 681) was >50% higher than in 2011. Median treatment success was 53% (interquartile range 40-70%) in the 25 countries reporting data for 30 021 MDR-TB cases who started treatment in 2010. Although progress has been noted in the ex...
The Lancet. Respiratory medicine, 2017
Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbi...
Respiratory Medicine
Aim: Europe has the highest documented caseload and greatest increase in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) of all World Health Organization (WHO) regions. This survey examines how recommendations for M/XDR-TB management are being implemented. Methods: TBNET is a pan-European clinical research collaboration for tuberculosis. An email survey of TBNET members collected data in relation to infection control, access to molecular tests and basic microbiology with drug sensitivity testing. Results: 68/105 responses gave valid information and were from countries within the WHO European Region. Inpatient beds matched demand, but single rooms with negative pressure were only available in low incidence countries; ultraviolet decontamination was used in 5 sites, all with >10 patients with M/ XDR-TB per year. Molecular tests for mutations associated with rifampicin resistance were widely available (88%), even in lower income and especially in high incidence countries. Molecular tests for other first line and second line drugs were less accessible (76 and 52% respectively). A third of physicians considered that drug susceptibility results were delayed by > 2 months. Conclusion: Infection control for inpatients with M/XDR-TB remains a problem in high incidence countries. Rifampicin resistance is readily detected, but tests to plan regimens tailored to the drug susceptibilities of the strain of Mycobacterium tuberculosis are significantly delayed, allowing for further drug resistance to develop.
The Lancet, 2010
Although progress has been made to reduce global incidence of drug-susceptible tuberculosis, the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis during the past decade threatens to undermine these advances. However, countries are responding far too slowly. Of the estimated 440 000 cases of MDR tuberculosis that occurred in 2008, only 7% were identifi ed and reported to WHO. Of these cases, only a fi fth were treated according to WHO standards. Although treatment of MDR and XDR tuberculosis is possible with currently available diagnostic techniques and drugs, the treatment course is substantially more costly and laborious than for drug-susceptible tuberculosis, with higher rates of treatment failure and mortality. Nonetheless, a few countries provide examples of how existing technologies can be used to reverse the epidemic of MDR tuberculosis within a decade. Major improvements in laboratory capacity, infection control, performance of tuberculosis control programmes, and treatment regimens for both drug-susceptible and drug-resistant disease will be needed, together with a massive scale-up in diagnosis and treatment of MDR and XDR tuberculosis to prevent drug-resistant strains from becoming the dominant form of tuberculosis. New diagnostic tests and drugs are likely to become available during the next few years and should accelerate control of MDR and XDR tuberculosis. Equally important, especially in the highest-burden countries of India, China, and Russia, will be a commitment to tuberculosis control including improvements in national policies and health systems that remove fi nancial barriers to treatment, encourage rational drug use, and create the infrastructure necessary to manage MDR tuberculosis on a national scale.