When selecting anti-TB drugs, we consider two properties: antibacterial (bactericidal and bacteristatic) and bacterial resistance inhibition activity. The most effective drugs in decreasing order for antibacterial activity are isoniazid, rifampin, and streptomycin, while those for resistance inhibition are isoniazid, rifampin, and ethambutol. The standard regimen for active tuberculosis is the combination of isoniazid, rifampin, ethambutol, and pyrazinamide. This four drug regimen offers a rapid clinical improvement and a significant fall in the bacterial count in a few months. Coughing and sputum will diminish and chest X-rays show improvements. Although bacteria may persist in the smears for some time, it should clear up eventually unless in the presence of drug resistance. The absence of radiological improvement in the first three months should cause concern and reevaluation of the regimen. Patient compliance and the bacteria's drug sensitivity should be closely monitored. Patient compliance is commonly enforced through directly observed therapy. Relapses usually occur within six months of the end of treatment. When TB becomes active again in a previously treated patient, it is highly likely that the bacteria will now be drug resistant. One should never add a single drug to a failing regimen. If the microorganism is resistant to the standard drugs, then it will be necessary to administer second-line drugs, such as ethionamide, protionamide, cycloserine, capreomycin, viomycin, and kanamycin, which are often more toxic.
Molecular studies of the mechanism of action of anti-TB drugs have revealed the genetic basis of drug resistance. Drug resistance is attributed primarily to the accumulation of mutations in the drug target genes. Co-administration of multiple drugs is the traditional strategy for preventing drug resistance. However, the emergence of multiple-drug resistant bacteria prompts researchers to develop mechanism-specific inhibitors and explore new and more effective drugs.