Mycobacterium tuberculosis chemotherapy

Mycobacterium tuberculosis is the causal organism of tuberculosis in humans. Allied strains cause infections in animals, e.g. bovine tuberculosis and tuberculosis in rodents. Due to the waxy nature of the cell wall this organism will resist desiccation and will survive in sputum. Tuberculosis has been largely eliminated by immunization and chemotherapy. 

Since the causative organism of leprosy, one of the world s six major diseases, Mycobacterium leprae, is closely related to Mycobacterium tuberculosis, thio-semicarbazones have also been used as second-line drugs in the chemotherapy of leprosy [38]. The most widely used in leprosy treatment has been thiacetazone, and structure-activity relationships for it are similar to those observed for antitubercular thiosemicarbazones [39, 40]. 

Pasca, M.R., Guglierame, P., De Rossi, E., Zara, F., and Riccardi, G. (2005) mmpL7 gene of Mycobacterium tuberculosis is responsible for isoniazid efflux in Mycobacterium smegmatis. Antimicrobial Agents and Chemotherapy, 49 (11),... 

Ha S-J, Jeon B-Y, Kim S-C, et al. (2003). Therapeutic effect of DNA vaccines combined with chemotherapy in a latent infection model after aerosol infection of mice with Mycobacterium tuberculosis. Gene Ther. 10(18) 1592-1599. 

Barrow EL, Winchester GA, Staas JK, Quenelle DC, Barrow WW. Use of microsphere technology for targeted delivery of rifampin to Mycobacterium tuberculosis-infected macrophages. Antimicrobial Agents and Chemotherapy. October 1998 42(10) 2682-2689. PubMed PMID 9756777. Pubmed Central PMCID 105919. 

The pathogenic bacteria Mycobacterium tuberculosis was found in 1882 by Robert Koch (1843-1910), and the discovery of rifampicin occurred 84 years after this event. Now, by treating with the combination of rifampicin and isonicotinic acid hydrazide (also known as isoniazid or INH, and described in Chapter 10), it became possible to completely control internal M. tuberculosis by chemotherapy in most cases since the 1970s. However, serious attention is now being paid to the appearance of drug-resistant strains of the microbe. 

About 1.8 billion individuals, or about one-third of the world s population, are infected with Mycobacterium tuberculosis, and most of these individuals have latent infection. Although malnutrition is a major risk factor for the progression of tuberculosis, tuberculosis control programs have tended to focus upon chemoprophylaxis and chemotherapy alone, rather than upon improvement of host nutritional status. For over one hundred years, cod-liver oil, a rich source of vitamins A and D, was used as a treatment for tuberculosis. The role of nutrition and tuberculosis remains a major area of neglect, despite the promise that micronutrients have shown as therapy for other types of infections and the long record of the use of vitamins A and D for treatment of pulmonary and miliary tuberculosis in both Europe and the United States. A recent clinical trial suggests that high dose vitamin A supplementation does not alter the morbidity of tuberculosis in children [65]. Studies have not been conducted which address the use of multivitamins and minerals or vitamins A plus D as an adjunct therapy for tuberculosis. 

BCG is a viable strain of Mycobacterium bovis that has been used for immunization against tuberculosis. It has also been employed as a nonspecific adjuvant or immunostimulant in cancer therapy but has been successful only in intravesical therapy for superficial bladder cancer. BCG appears to act at least in part via activation of macrophages to make them more effective killer cells in concert with lymphoid cells in the cellular efferent limb of the immune response. Lipid extracts of BCG as well as nonviable preparations of Corynebacterium parvum may have similar nonspecific immunostimulant properties. A chemically defined derivative of the BCG cell wall, [Lys18]-muramyl dipeptide, has been licensed in Japan to enhance bone marrow recovery after cancer chemotherapy. 

Mycobacteria cause tuberculosis, Mycobacterium avium complex (MAC) disease, and leprosy. Tuberculosis remains the leading worldwide cause of death due to infectious disease. First-line agents for the chemotherapy of tuberculosis combine the greatest efficacy with an acceptable degree of toxicity (Table 47-1), and the large majority of patients with tuberculosis are treated successfully with these drugs. Occasionally, it may be necessary to resort to second-line drugs. 

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