Mycobacterium tuberculosis drug resistance

This process was undoubtedly developed for the manufacture of pyrazinamide (Zinamide, etc.),1696 a second-line drug for Mycobacterium tuberculosis infections, resistant to more effective and less toxic agents. Thus a mixture of 2-methyl-pyrazine (323), ammonia, oxygen, and steam is passed (at 400°C) over an alumina- or pumice-supported catalyst comprising one to three oxides of Ce, Cr, Mo, Mn, P, Sb, Ti, or (most importantly) V the main product (in up to 90% yield) is 2-pyrazinecarbonitrile (324), easily converted into 2-pyrazinecarboxamide... 

Isoniazid (INH) is still the most widely used drug in the treatment of tuberculosis (TB) and has high activity against Mycobacterium tuberculosis, although resistant strains have emerged. INH is used in combination with drugs such as rifampicin and pyrazinamide to reduce the chance of inducing resistant strains of the mycobacterium. 

The advent of multidrug resistant strains of Mycobacterium tuberculosis (MDR-TB) has led to increased fears of untreatable infections by serious pathogens. Rifampicin, streptomycin and, occasionally, the quinolones are drugs used in the treatment of mycobacterial infections and resistance to those agents is as described previously. There... 

Gillespie SH Evolution of drug resistance in Mycobacterium tuberculosis Clinical and molecular perspective. Antimicrob Agents Chemother 2002 46 267-274. 

Fietta A, Cascina A, Meloni F, Morosini M, Casali L, Bono L, Minoli L, Marone P A 10-year survey of Mycobacterium tuberculosis isolates in Pavia and their drug resistance A comparison with other Italian reports. J Chemother 2002 14 33-40. 

Mycobacterium tuberculosis Add streptomycin or ethambutol as a fourth drug in a regimen containing isoniazid (INH), rifampin, and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH or rifampin resistance is very low. Streptomycin also is indicated for therapy of tuberculosis when one or more of the above drugs is contraindicated because of toxicity or intolerance. 

Ethambutol is a water-soluble, heat-stable compound that acts by inhibition of arabinosyl transferase enzymes that are involved in cell wall biosynthesis. Nearly all strains of M tuberculosis and M. kansasii and most strains of Mycobacterium avium-intracellulare are sensitive to ethambutol. Drug resistance relates to point mutations in the gene (EmbB) that encodes the arabinosyl transferases that are involved in mycobacterial cell wall synthesis. 

The MIC/MBC ratio was 1 4 for sensitive isolates, while it was 1 2 for drug-resistant Mycobacterium tuberculosis isolates. The BA values against the sensitive isolates were 0.19 and 0.50, respectively, for days 7 to 32. 

Shi, R. et al. Temperature-mediated heteroduplex analysis for the detection of drug-resistant gene mutations in clinical isolates of Mycobacterium tuberculosis by denaturing HPLC, SURVEYOR nuclease. Microb. Infect. 2006, 8, 128-135. 

Drug therapy has transformed tuberculosis from a disabling and often fatal disease into one in which almost 100% cure is obtainable, although the recent emergence of multiple drug resistant strains of Mycobacterium tuberculosis (MDRTB) in developed... 

Treatment problems that can arise are mainly of two types adverse reactions (collateral, toxic, or hypersusceptibility reactions), and initial or acquired resistance of Mycobacterium tuberculosis, Mycobacterium bovis, or non-tuberculous mycobacteria to one or more of the antituberculosis drugs. The latter probably only occurs when the patient has not taken the full combination or the full doses of the drugs all the time. Combination formulations are thus particularly useful. Multidrug-resistant tuberculosis, defined as resistance against at least isoniazid and rifampicin, is the most clinically relevant form of resistance to treatment worldwide. 

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