Tuberculosis bacterial resistance

Of increasing concern is the development of mutant strains of tuberculosis that are resistant to many of the aiititubercular drug s currently in use. Bacterial resistance develops, sometimes rapidly, with the use of anti-tubercular drag s. Treatment is individualized and... 

Microorganisms surviving M. tuberculosis Bacterial spores HBV and prions as in Creutzfeldt-Jakob disease Bacterial spores Prions Extreme challenge of resistant bacterial spores Prions (insufficient data)... 

Consumption of fish oil in excess can generate immunotoxic effects in laboratory animals. Rats fed a 17% fish oil diet had reduced wound-healing responses when compared to com oil [59], In a mouse model of bacterial resistance to S. typhimurium, lower survival rates were reported for those animals that ingested a 20% fish oil diet over 15 days [59], Similar fish oil-induced effects in guinea pigs were noted in a study of experimental tuberculosis leading the authors to conclude that this treatment resulted in decreased resistance to infectious disease. The consumption of fish oil has also been reported to result in alterations of hemostatic parameters such as platelet production and function. However, there is no indication that at doses normally consumed by humans, immunotoxicity will occur. 

Pharmacology Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis. It inhibits the onset of bacterial resistance to streptomycin and isoniazid. The mechanism of action has been postulated to be inhibition of folic acid synthesis (but without potentiation with antifolic compounds) or inhibition of synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis. 

Bacteriostatic against Mycobacterium tuberculosis. It inhibits the onset of bacterial resistance to streptomycin and INH. 

Moreover, the discovery of effective agents to treat infectious diseases such as malaria and tuberculosis is inherently difficult - bacterial resistance and viral mutations are common, so that therapies have very limited efficacy, and a discovery platform in infectious disease is a multi-year commitment of financial and other research resources. Again, developmental failures are expensive and R D expenditures are what economists call "sunk costs," meaning that the costs are not recoverable in the future. 

Microorganisms surviving M. tuberculosis Bacterial spores Extreme challenge of resistant... 

Drug inactivation. Bacterial resistance to aminoglycosides and /3-lactam antibiotics usually results from production of enzymes that modify or destroy the antibiotic, respectively. A variation in this mechanism—the failure of bacteria to activate a prodrug—commonly underlies resistance of Mycobacterium tuberculosis to isoniazid. 

Capreomycin (capasiat) is an antimycobacterial cyclic peptide elaborated by Streptococcus capreolus. Bacterial resistance to capreomycin develops when it is given alone such microorganisms show cross-resistance with kanamycin and neomycin. Capreomycin is used only in conjunction with other appropriate drugs in treatment of pulmonary tuberculosis when bactericidal agents cannot be tolerated or when causative organisms have become resistant. 

An important problem in the chemotherapy of tuberculosis is bacterial resistance, primarily due to poor patient adherence. To prevent noncompliance and the attendant development of drug-resistant tuberculosis, directly observed therapy is advisable for most patients (i.e., a health care provider observes the patient take the medications 2—5 times weekly). 

Although the advent of the antibiotics revolutionized the treatment of bacterial infections, tuberculosis has proven unusually resistant to chemotherapeutic attack. Although many antibiotics are effective to some extent in arresting the progress of... 

The three standard drugs used in the treatment of tuberculosis were streptomycin (considered above), -aminosalicylic acid (PAS) and isoniazid (isonicotinylhydrazide, INH synonym, isonicotinic acid hydrazine, INAH). The tubercle bacillus rapidly becomes resistant to streptomycin, and the role of PAS was mainly that of preventing this development of resistance. The current approach is to treat tuberculosis in two phases an initial phase where a combination of three dmgs is used to reduce the bacterial level as rapidly as possible, and a continuation phase in which a combination of... 

Mycobacteria are more resistant than other non-sporulating bacteria to a wide range of biocides. Examples of such organisms axe Mycobacterium tuberculosis, theM avium-intracellulare (MAI) group andM. chelonae (M. chelonei). Of the bacteria, however, the most resistant of all to biocides are bacterial spores, e.g. Bacillus subtilis, B. cereus. 

Multidrug resistant tuberculosis (TB) The presence of at least 1% of Mycobacterium strains in a bacterial population or culture that are resistant to at least isoniazid and rifampin. 

Rifampin inhibits the bacterial enzyme that catalyzes DNA template-directed RNA transcription, i.e DNA-de-pendent RNA polymerase. Rifampin acts bactericidally against mycobacteria (M. tuberculosis, M. leprae), as well as many gram-positive and gram-negative bacteria It is well absorbed after oral ingestion. Because resistance may develop with frequent usage, it is restricted to the treatment of tuberculosis and leprosy (p. 280). 

Pharmacology Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase, but does not inhibit the mammalian enzyme. Cross-resistance has only been shown with other rifamycins. Rifampin at therapeutic levels has demonstrated bactericidal activity against intracellular and extracellular Mycobacterium tuberculosis organisms. Pharmacokinetics ... 

Streptomycin Prevents bacterial protein synthesis by binding to the S12 ribosomal subunit (see also Chapter 45) Bactericidal activity against susceptible mycobacteria Used in tuberculosis when an injectable drug is needed or desirable and in treatment of drug-resistant strains IM, IV renal clearance (half-life 2.5 h) administered daily initially, then 2 x week Toxicity Nephrotoxicity, ototoxicity... 

Rifapentine is an analog of rifampin. It is active against both M tuberculosis and Mavium. As with all rifamycins, it is a bacterial RNA polymerase inhibitor, and cross-resistance between rifampin and rifapentine is complete. Like rifampin, rifapentine is a potent inducer of cytochrome P450 enzymes, and it has the same drug interaction profile. Toxicity is similar to that of rifampin. Rifapentine and its microbiologically active metabolite, 25-desacetylrifapentine, have an elimination half-life of 13 hours. Rifapentine is indicated for treatment of tuberculosis caused by rifampin-susceptible strains. The dose is 600 mg once or twice weekly. Whether rifapentine is as effective as rifampin has not been established, and rifampin therefore remains the rifamycin of choice for treatment of tuberculosis. 

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