An update on pathogenesis and management of tuberculosis with special reference to drug resistance

Drug resistance in tuberculosis (TB) is a global problem and both developed as well as under developed parts of the world are predisposed to drug resistant TB. Multiple drug resistant–TB (MDR-TB) designates the very strain of the pathogen which is resistant to at least two primary anti-TB drugs isoniazid and rifampicin. This strain after acquiring a further bacillary resistance to any second line injectable drug and any of the fluoroquinolones is termed as extensively drug resistant TB (XDR-TB). The present review is endeavored to recapitulate the contemporary state of multidrug resistance in TB, the pathophysiology and recent developments for a rapid and reliable detection of the infection and management of MDR-TB. The challenge of MDR-TB management must be embarked on by skilled doctors at operational BCL-3 laboratory facilities where all allied services for the in-vitro sensitivity testing of mycobacteria are available because it includes extended treatment with costly second–line drugs containing meticulous toxicity. Even more dreaded are some newly emerging TB strains namely XDR-TB which is resistant to many more anti-TB agents (such as isonicotinic acid hydrazide and rifampicin plus second line injectable streptomycin, amikacin and kanamycin). Newer discovery of novel anti-TB drugs through recent research regarding the management of drug resistant tuberculosis would help avert and eradicate MDR-TB as well as XDR-TB. For shortening of the TB–treatment regimen, a few drugs, especially gatifloxacin and moxifloxacin, are being tested, while PA-824, OPC-67683 and TMC-207 are also being studied for both drug resistant and drug susceptible disease. Given the past global trends in MDR-TB, if aggressive preventive and management strategies are not implemented against it, XDR-TB would emerge to a larger extent which would severely cripple global control efforts of TB. However, very recently a newly discovered drug bedoquinoline is demonstrating strong promise towards containment of XDR-TB.