Recent Trends in Treatment of Multidrug Resistant-Tuberculosis-A Review (original) (raw)

Clinical management of drug resistant tuberculosis

Asian Journal of Medical Sciences, 2014

Despite the introduction 40 years ago of the inexpensive and effective four-drug (isoniazid, rifampicin, pyrazinamide and ethambutol) treatment regimen, tuberculosis (TB) continues to cause considerable morbidity and mortality worldwide. This is because of development of drug resistance in tuberculosis strains, usually called as MDR/XDR-TB. Consequently, novel drugs and regimens for management of these drug resistant TB forms are emerging. Such regimens probably utilize both repurposed drugs and new chemical drugs. This article covers current concepts and recent advances in TB drug discovery and development. An updated review of the mechanisms of action and resistance of the main old and new anti-tuberculosis agents has been described. The consensus statements from RNTCP for management of MDR/XDR-TB have also been discussed.

WHAT'S NEW IN THE TREATMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS? (Atena Editora)

WHAT'S NEW IN THE TREATMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS? (Atena Editora), 2023

Introduction: The current Tuberculosis epidemic represents a major public health problem. The issue gained prominence due to the increasing incidence of Mycobacterium tuberculosis strains resistant to first-line antituberculosis agents, posing a threat to disease control and management strategies. Objectives: To identify in the literature an overview of the current evidence on the management of multidrug-resistant tuberculosis. Methodology: A bibliographic review was carried out, through research in the SciELO databases, the Virtual Health Library and in data repositories. 4 original articles and 1 document made available by the Ministry of Health, published from 2018 to 2022, were selected. Descriptors used: MDR-TB, Multidrug-resistant Tuberculosis, Antituberculous agents. Results and Discussion: Multidrug-resistant Tuberculosis (MDR-TB) is described by resistance to the drugs rifampicin and isoniazid, used as a standard therapeutic scheme. The disease poses challenges in its treatment, such as a high failure rate and high risk of adverse events, mainly due to the lack of standardization and global regulation of the drugs used. Currently, excluding restrictions, treatment lasts for 8 months using capreomycin associated with levofloxacin, terizidone, ethionamide and pyrazinamide, followed by 10 months of treatment with levofloxacin associated with terizidone and ethionamide. Bedaquiline (BDQ), a diarylquinoline with bactericidal and sterilizing action, is recommended by the World Health Organization (WHO) in long-term regimens and in combination with three other effective drugs. The proposed administration is oral, aiming to optimize treatment outcomes and reduce toxicity associated with injectable drugs. A retrospective observational study conducted in 15 countries reported the outcomes of 428 cases treated with BDQ-containing regimens. The bacilloscopy and sputum culture conversion rates achieved at the end of treatment were 88.7% and 91.2%, respectively; the success rate in the cohort as a whole was 77%. Delamanid, a drug from the nitroimidazole class with bactericidal action, is recommended under the same conditions described for BDQ, prescribed when drugs from the previous groups cannot be used. Recent evidence suggests that the bedaquiline-delamanid combination is well tolerated in cases where few treatment options are available. The use of beta-lactam antibiotics associated with a beta-lactamase inhibitor, such as carbapenems associated with clavulanic acid, proved to be a therapeutic alternative. The combination showed a potent effect against M. tuberculosis - the cohorts performed had a success rate between 57.3% and 80.3%. However, the use of carbapenems is restricted to patients with severe presentation of the disease and therapeutic failure in second-line treatment. Factors such as high costs and lack of oral formulations contribute to their limited use. Conclusion: Through the study carried out, it was possible to confirm the challenges of MDR-TB therapy. Drugs such as delamanid, bedaquiline and carbapenems proved to be promising alternatives for the treatment of MDR-TB, demonstrating the importance of searching for new therapeutic strategies that aim not only to improve the current scenario of the disease, but also to improve the quality of care. patient's life and adherence to treatment.

Treatment of drug-resistant tuberculosis

Infection and Drug Resistance, 2011

What is the best approach to the treatment of drug-resistant tuberculosis (TB)? Results: Evidence-based treatment of drug-susceptible TB is the best means of preventing the development of drug-resistant disease. Suspecting the possibility of drug-resistant TB, and prompt detection of all forms of drug-resistant TB, not only multidrug-resistant and extensively drug-resistant TB, should be part of the algorithm for diagnosis and management of all patients with active TB. Implementation: Treatment of all forms of drug-resistant TB must be tailored to the specific form of resistance with appropriate and effective drug regimens.

Treatment of Drug-Resistant Tuberculosis: Current Status

Annals of the National Academy of Medical Sciences (India)

Drug-resistant tuberculosis (DR-TB) has been an area of growing concern and posing threat to human health worldwide. The treatment has been defined for all types of DR-TB with or without newer anti-TB drugs. multi-DR-TB (MDR-TB) patients have now choice of two types of regimen, shorter and longer regimens. Shorter regimen for treatment of subset of MDR-TB patients who have not been previously treated with second line drugs and in whom resistance to fluoroquinolones and second-line injectable agents has been excluded is given for 9 to 11 months. A longer regimen of at least five effective anti-TB drugs (ATDs) during the intensive phase is recommended, including pyrazinamide and four core second-line ATDs. Intensive phase, including injectables, should be given for at least 8 months. The total duration of treatment is at least 20 months, which can be prolonged up to 24 months depending on the response of the patient. World Health Organization (WHO) has recently revised the grouping of...

Current Treatment of Multidrug Resistant and Rifampicin Resistant Tuberculosis

The Indian Journal of Chest Diseases and Allied Sciences

Multidrug-and rifampicin-resistant tuberculosis (MDR-TB/RR-TB) has been an area of growing concern to human health worldwide and posing a threat to the control of tuberculosis (TB). Proper treatment of every diagnosed case of MDR-TB/RR-TB is of paramount importance. For the treatment of MDR-TB/RR-TB, standardised, empirical and individualised approaches have been laid down. There can be two types of treatment regimen-conventional and shorter regimen. A conventional regimen of at least five effective anti-TB drugs (ATDs) during the intensive phase is recommended, including pyrazinamide and four core second-line ATDs. Intensive phase including injectables should be given for atleast eight months. The total duration of the treatment is atleast 20 months which can be prolonged upto 24 months depending upon the response of the patient. Shorter regimen for the treatment for subset of MDR-TB/RR-TB patients who have not been previously treated with secondline drugs and in whom resistance to flouroquinolones and second-line injectable agents has been excluded can given for 9-11 months. The intensive phase of 4 to 6 months consists of kanamycin, high dose moxifloxacin, ethionamide, clofazimine, pyrazinamide, high-dose isoniazid and ethambutol, followed by the continuation phase of five months that consist of high dose moxifloxacin clofazimine, pyrazinamide and ethambutol. Extra-pulmonary MDR-TB/RR-TB including TB meningitis is treated with a longer regimen with same duration as pulmonary MDR-TB/RR-TB. All patients initiated on treatment and their family members should be intensively counselled prior to the treatment initiation and during all the follow-up visits. Surgery may be considered with recommended MDR-TB/RR-TB regimen only with good surgical facilities, trained and experienced surgeons and with careful selection of the patients. The treatment outcomes varied from 50% to 80% in different studies.

Drug Resistance in Mycobacterium tuberculosis

Over 95% of tuberculosis (TB) cases and deaths among adults occur in developing countries. The emergence, management of cases, and spread of drug-resistant strains of Mycobacterium tuberculosis is one of the biggest challenges faced by national tuberculosis control programs. Multidrug-resistant TB (MDR-TB), defined as resistance to isoniazid and rifampicin, the two most potent anti-TB drugs, is increasing. MDR-TB is difficult and expensive to treat. Extensively drug-resistant TB (XDR-TB), defined as MDR-TB with additional resistance to a fluoroquinolone and one or more of the injectable anti-TB drugs, has been reported in many countries. Due to lack of diagnostic capacity, particularly in developing countries, the burden of MDR-TB and XDR-TB is not well known. Detection of drug-resistant TB is hindered by the difficulty and length of time required for its diagnosis while using conventional indirect drug susceptibility testing. Development and implementation of rapid methods for the diagnosis of drug-resistant TB are essential to long-term effective control of TB. Presented in this chapter are the terminology used in TB drug resistance, anti-TB drug groups, development and mechanism of drug resistance, and the conventional and new rapid susceptibility testing techniques. Finally, the treatment, control, and surveillance for TB drug resistance are introduced.

Multi drug resistant tuberculosis: a challenge in the management of tuberculosis

African Journal of Health Sciences, 2008

Multi drug resistant tuberculosis (MDR-TB) will not usually respond to short course chemotherapy. Unless the individual infected with this bug is treated appropriately, they can continue spreading resistant strains in the community and further fuel the tuberculosis epidemic. Diagnosis requires drug sensitivity testing and the capability to do this is not widely available. Multi drug resistant tuberculosis has been reported all over Africa but the prevalence is still low. The treatment is not only expensive but also quite prolonged and compliance cannot be overemphasized. The recent outbreaks of extensive drug resistant TB further complicate the management and control of the disease. This is a perspective on challenges of managing MDR TB and its effect on the control program the information presented is gathered from published data.

New treatment options for multidrug-resistant tuberculosis

Therapeutic Advances in Respiratory Disease, 2012

Despite the development of effective treatments, tuberculosis (TB) remains a major health problem. TB continues to infect new victims and kills nearly 2 million people annually. The problem is much greater in resource-limited countries but is present worldwide. Inadequate public health resources, cost, the obligatory long treatment period, and adverse drug effects contribute to treatment failures and relapses. Drug-resistant Mycobacterium tuberculosis (MTB) strains arise spontaneously and are propagated by inadequate treatment. According to World Health Organization global data, 17% of MTB strains in new, previously untreated cases are resistant to at least one drug. Approximately, 3.3% of new MTB cases are resistant to both isoniazid and rifampin, also called multidrug resistant (MDR), and rates of MDR-TB are greater than 60% in previously treated patients in some countries. Approximately 5% of cases of MDR-TB are also resistant to fluoroquinolones and to injectable drugs, and are called extensively drug resistant (XDR). Recently, XDR strains have been isolated that are also resistant to all standard second-line anti-TB medications. Successful drug treatment of TB with complex resistance profiles is virtually impossible with currently available drugs. There is a desperate need for new compounds that cure strains resistant to currently available drugs and for drugs that are better tolerated and will shorten treatment regimens. In the short term, new strategies for the management of drug-resistant TB with currently available drugs are being explored. These include the use of high-dose isoniazid, substitution of rifabutin in a small proportion of rifampin-resistant cases, linezolid, fluoroquinolones, and phenothiazines. A number of novel drugs are undergoing clinical testing and will hopefully be available in the near future. These include the newer oxazolidinones, diarylquinolines, nitroimidazopyrans, ethenylenediamines, pyrroles, and benzothiazinones.