Drug-Resistant Tuberculosis: Causes, Diagnosis and by Shui Ngy, Zhou K'ung, Suhail Ahmad, Eiman Mokaddas, Jarmila

By Shui Ngy, Zhou K'ung, Suhail Ahmad, Eiman Mokaddas, Jarmila Vinsova, Martin Kratky, Ahmed Kamal

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Extra resources for Drug-Resistant Tuberculosis: Causes, Diagnosis and Treatments (Virology Research Progress)

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Tuberculosis strains also contain mutations at codon 464 or 495 of the gyrB gene [207, 210]. Ethionamide (ETH), a structural analog of INH is an important second-line drug used for the treatment of MDR-TB and also shares the target with INH. Similar to INH, ETH is also a pro-drug, however, it is activated by a different mechanism than INH. The ETH is activated by a monooxygenase (encoded by ethA) while INH is activated by catalase-peroxidase (encoded by katG) [104-106, 114, 115]. The ethA catalyses a two step activation of ETH to its active form (4-ethyl-4-amidopyridine).

Nearly 20-30% of PZA resistant M. tuberculosis isolates do not contain a mutation within pncA suggesting that other mechanism conferring PZA resistance exist in these isolates [94, 117, 140, 174]. Ethambutol (EMB) is a synthetic compound that is used as an alternative first-line drug for SM in the standard combination therapy with three other first line drugs, INH, RIF and PZA in the four-drug regimens advocated by World Health Organization under the DOTS strategy. This is mainly because global data on drug resistance patterns have shown that resistance of M.

30 Suhail Ahmad and Eiman Mokaddas The infections caused by monoresistant M. tuberculosis strains to most of the first-line drugs can be managed as the available first-line and some bactericidal second-line agents ensure successful treatment. However, treatment failure is more likely among resistant cases than among TB patients infected with fully susceptible strains of M. tuberculosis. The treatment duration is nearly same for TB caused by EMB- or SM-monoresistant strains and the risk of treatment failure is also nearly same as with fully susceptible TB [72].

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