Chemotherapy by antitubercular drugs has revolutionized the treatment of tuberculosis. Antituberculous therapy destroys the tubercle bacilli, thereby preventing further complications of early primary disease and progression of disease. Therapy with antituberculous drugs causes disappearance of caseous or granulomatous lesions. Antituberculous drugs are classified as first-line and second-line drugs as follows:
First-line antitubercular drugs include rifampicin, INH, etham-butol, streptomycin, and pyrazinamide. All first-line drugs with the exception of ethambutol are bactericidal. These drugs have less toxicity and show greater efficacy than second-line drugs. Both INH and rifampicin are effective against tubercle bacilli in necrotic foci and intracellular mycobacteria. In contrast, strep-tomycin, aminoglycosides, and capreomycin show poor intra-cellular penetration.
Combination of four drugs (INH, rifampicin, pyrazinamide, and ethambutol) is given for a period of 6–7 months for treat-ment of smear-positive cases of tuberculosis. These are given three times a week for first 2 months, followed by only two drugs (INH, rifampicin) three times a week.
Emergence of natural drug resistance in M. tuberculosis is a major problem in chemotherapy of tuberculosis. This occurs by mutation with a frequency of appropriately 106 cell divisions.
Multiple drug resistance: If the cases of tuberculosis aretreated with a single antitubercular drug, the subpopulation of tubercle bacilli susceptible to that drug are killed, whereas populations not susceptible to the drug continue to multi-ply. Therefore, the use of multiple antitubercular agents in the treatment of tuberculosis is useful. The emergence of multidrug-resistant tuberculosis (MDR-TB) is a very seri-ous problem and is defined as resistance to rifampicin and INH with or without resistance to one or more other drugs. This is because rifampicin and INH form the mainstay of short-term chemotherapy, and M. tuberculosis strains resis-tant to both these drugs are unlikely to respond to treatment. Multiple drug resistance (MDR) is of two types—primary and secondary.
Primary MDR is defined as development of resistance toantitubercular treatment in an individual who has no history of antitubercular treatment. It usually occurs:
· In patients residing in areas with a high prevalence of drug-resistant M. tuberculosis,
· In those exposed to drug-resistant contagious tuber-culosis, and
· In those with HIV infections and in the individuals using intravenous drugs.
Secondary MDR is defined as emergence of antitubercularresistance during the course of infection and antitubercular treatment. It develops usually:
· In patients treated with inappropriate drug regimen and
· In those not taking antituberculous drugs regularly.
The initial antitubercular regimen for patients with MDR includes four drugs. These contain at least four bactericidal drugs, such as INH, rifampicin, pyrazinamide, and either strepto-mycin or another aminoglycoside or a high dose of ethambutol.
Second-line antitubercular drugs are used for the cases of tuber-culosis where first-line drugs become ineffective. These include a large number of old and new drugs, such as ciprofloxacin, cycloserine, ethionamide, kanamycin, ofloxacin, levofloxacin, capreomycin, and others. Directly observed therapy (DOT) is a method being recently followed for treatment of cases of tuber-culosis. The DOT is extremely useful to prevent the emergence of drug resistance by ensuring patient compliance.