Category: 10. Chemotherapeutic Agents

Disease caused by “atypical” mycobacteria is often less severe than tuberculosis and not communicable from person to person. M avium complex is an important and common cause of disseminated disease in late stages of AIDS. Azithromycin or clarithromycin, plus ethambutol are effective and well-tolerated regimen for treatment of disseminated disease. Some authorities recommend use of…

Directly Observed Treatment Short Course (DOTS) Used in new Pulmonary TB smear positive patients; new Pulmonary TB smear negative and Extrapulmonary TB patients who are seriously ill; TB in children < 6 years. It consists of 8 weeks of treatment with Streptomycin, Rifampicin, Isoniazid and Pyrazinamide during the intensive phase followed by 6 monthes of…

The duration of therapy for a patient with tuberculosis depends upon the severity of the disease, the organ affected and the combination of agents. There are two phases in the treatment of tuberculosis; the intensive phase, which lasts 8 weeks, makes the patients noninfectious. The continuation phase, which lasts 6 months or more and at…

Most tubercle bacilli are inhibited by streptomycin. Streptomycin penetrates into cells poorly, and thus it is active mainly against extracellular tubercle bacilli. Streptomycin crosses the blood- brain barrier and achieves therapeutic concentrations with inflamed meninges. It is employed principally in individuals with severe, possibly life-threatening forms of tuberculosis (meningitis and disseminated disease), and in treatment…

Pyrazinamide (PZA) is a relative of nicotinamide, stable, slightly soluble in water. Drug is taken up by macrophages and kills bacilli residing within this acidic environment. PZA is well absorbed from the gastrointestinal tract and widely distributed in body tissues, including inflamed meninges. Tubercle bacilli develop resistance to pyrazinamide fairly readily. Major adverse effects of…

Ethambutol inhibits synthesis of mycobacterial cell wall. Ethambutol is well absorbed from the gut. It accumulates in renal failure. Ethambutol crosses the blood-brain barrier only if the meninges are inflamed. Ethambutol hydrochloride given as a single daily dose in combination with INH or rifampin for the treatment of tuberculosis. The higher dose is recommended for…

Rifampin is administered together with INH, ethambutol, or another antituberculous drug in order to prevent emergence of drug resistant mycobacteria. Rifampin is an alternative to INH for prophylaxis in patients who are unable to take INH or who have had close contact with a case of active tuberculosis caused by an INH-resistant, rifampin-susceptible strain.

First-Line Antimycobacterial Drugs Members: Isoniazid (INH), rifampin, pyrazinamide, ethambutol, and streptomycin are the five first-line agents for treatment of tuberculosis. INH and rifampin are the two most active drugs. Isoniazid (INH) INH is the most active drug for the treatment of tuberculosis caused by susceptible strains. It is structurally similar to pyridoxine. It is bactericidal…

Mycobacterial infections are the most difficult of all bacterial infections to cure. Mycobacteria are slowly growing organisms (can also be dormant) and thus completely resistant to many drugs, or killed only very slowly by the few drugs that are active. The lipid-rich mycobacterial cell wall is impermeable to many agents. A substantial proportion of mycobacterial…

The half-life of trimethoprim and sulfamethoxazole is similar. Trimethoprim, given together with sulfamethoxazole, produces sequential blocking in this metabolic sequence, resulting in marked enhancement of the activity of both drugs. The combination often is bactericidal, compared to the bacteriostatic activity of a sulfonamide alone. Clinical uses: Trimethoprim-sulfamethoxazole is effective treatment for Pneumocystis carinii pneumonia, shigellosis,…