Drug Resistant Tuberculosis

Tuberculosis (TB) is a disease widespread throughout the world caused by Mycobacterium tuberculosis. Despite the strict developed strategies for TB control and significant increase in knowledge of the epidemiology of tuberculosis as well as mechanisms for survival of causative agent of tuberculosis, the disease remains one of the most common and deadly.

Due to developing genetic mutations in any quite large population of Mycobacteria tuberculosis, there are naturally formed mutant strains with drug resistance. At the same time due to development of resistance to one drug, there is greater tendency of mycobacteria to further acquiring resistance to other drugs, which leads to emergence of strains resistant to multiple drugs simultaneously. Patients with multidrug-resistant tuberculosis can be sources for the spread of resistant strains of mycobacteria, which leads to identification of "primary" drug resistance in patients with newly diagnosed tuberculosis.

Multi Drug-Resistant (MDR) TB is treatable and curable by using second-line drugs. However, second-line treatment options are limited and require extensive chemotherapy (up to 2 years of treatment) with medicines that are expensive and toxic.

In some cases, more severe drug resistance can develop. Extensively Drug-Resistant TB (XDR-TB) is a more serious form of MDR-TB caused by bacteria that do not respond to the most effective second-line anti-TB drugs, often leaving patients without any further treatment options.

Additionally, people living with HIV are 20 to 30 times more likely to develop active TB disease than people without HIV.HIV and TB form a lethal combination, each speeding the other's progress. In 2016 about 0.4 million people died of HIV-associated TB. About 40% of deaths among HIV-positive people were due to TB in 2016. In 2016, there were an estimated 1.4 million new cases of TB among people who were HIV-positive.

In 2016, MDR-TB remains a public health crisis and a health security threat. WHO estimates that there were 600 000 new cases with resistance to rifampicin – the most effective first-line drug – of which 490 000 had MDR-TB. The MDR-TB burden largely falls on 3 countries – India, China and the Russian Federation – which together account for nearly half of the global cases.

India has highest burden of both TB and MDR-TB based on estimates reported in Global TB Report 2016. An estimated 1.3 lakh incident multi-drug resistant TB patients emerge annually in India which includes 79000 MDR-TB Patients estimates among notified pulmonary cases. India bears second highest number of estimated HIV associated TB in the world. An estimated 1.1 lakh HIV associated TB occurred in 2015 and 37,000 estimated number of patients died among them.

Control and treatment of MDR-TB became one of the priorities due to awareness of the problem, increase of material and technical facilities as well as distribution of evidence-based medicine. Intensive introduction of alternative and additional treatment strategies is required in order to take control of the serious problem of MDR-TB.

The pipelines for new diagnostics, drugs, treatment regimens and vaccines are progressing, but slowly. Increased investment in research and development is needed.

The treatment of drug resistant TB has always been more difficult than the treatment of drug susceptible TB. It requires the use of second line or reserve drugs that are more costly and cause more side effects. Also the drugs must be taken for up to two years. Fluoroquinolones (FQs) are effective against Mycobacterium tuberculosis and are used in the treatment of multidrug-resistant tuberculosis (MDR-TB). As measured by the in vitro activity against Mycobacterium tuberculosis, the most potent of the currently available fluoroquinolones are, in descending order, moxifloxacin, gatifloxacin, levofloxacin, ofloxacin, and ciprofloxacin. M. tuberculosis clinical isolates that demonstrate high-level phenotypic resistance to fluoroquinolones, which appears to be predominantly due to gyrA mutations, exhibit cross-resistance to all six important fluoroquinolones. Patients with prior exposure to any of the quinolones are likely to develop resistance to other quinolones. Quinolones being broad spectrum antibacterial agents, their widespread and indiscriminate use, often in subtherapeutic doses, is likely to rapidly enhance quinolone-resistant organisms, including mycobacteria. There is rampant use of FQ drugs for undiagnosed respiratory infections in India, which has contributed to the emergence of FQ resistance in M. tuberculosis, which may in turn influence the clinical outcome of MDR-TB patients. For a long time now there has been no new established drug available for MDR TB. At present we are left with few bacteriostatic antitubercular drugs. Reports of quinolone-resistant tuberculosis are constantly pouring in and should act as a warning sign for the bleak future of cases of MDR-TB, because we are rapidly losing a very effective group of drugs for the management of such cases. Moreover, it is recommended that ofloxacin is phased out from MDR-TB regimens and ciprofloxacin is never used due to the limited evidence for its effectiveness.

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