Front line Tuberculosis drugs: what are prescribed and why

As with most powerful medications those used to treat tb can have serious side affects which should be monitored by caregivers
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Front line Tuberculosis drugs: what are prescribed and why

#1 Post by auntiebi0tic » Wed Jan 15, 2020 6:38 pm

The current accepted first-line therapy is a combination of the drugs rifampicin, isoniazid (INH), pyrazinamide, and ethambutol. After two months, the number of drugs is reduced. A typical treatment for a standard (i.e. non-drug resistant) strain of TB is 2HRZE / 4HR (= two months of INH, rifampin, pyrazinamide and ethambutol followed by four months of Rifampin and INH). The number of relapses is about 2-3% this way. Medication can be given two or three times per week (different/higher dosages) with the same results as daily therapy.

Streptomycin was once included in first-line therapy, but has since lost popularity as it has significant toxic effects. it also does not have an oral preparation, making it harder to administer and reducing patient compliance to therapy.

Why four drugs? If only one drug is given, the number of bacteria in the patient is so large that, there is a very high chance that (because of random mutation) some of them will be resistant to the drug. Thus a single drug will result in an initial improvment but most often not cure the patient as eventually the few resistant bacterial present cells will take over (be selected). There is evidence that up to 70% of patients being treated with INH only will develop INH-resistant strains. This drug resistant form will then be significantly more difficult to treat effectively. In addition, INH by itself is only bacteriostatic, therefore being only able to kill mycobacteria that are dividing rapidly.

Repeatedly taking a series of different drugs can result in highly resistant bacteria being selected which may be extremely difficult and expensive to treat. The DOTS protocol can help to avoid this.

INH and ethambutol are bacteriostatic agents that are only able to kill rapidly dividing mycobacteria, rifampicin is a bactericidal agent that kills the remaining bacteria, pyrazinamide acts well against the intracellular bacteria which are dormant inside macrophages and other cells. Rifampicin is the drug that provides the best "sterilization"; this means that it will kill dormant bacteria very well in order to lower the number of relapses after a successful treatment.

Streptomycin is used if the initial 4-drug therapy fails, often in conjunction with other second-line drugs such as capreomycin, cycloserine, new macrolides, quinolones, and protionamide. Streptomycin and capreomycin are not available as oral medications and must be injected. The newer linezolid (of the oxazolidinone class) has anti-mycobacterial activity in the laboratory, and is a promising drug to be evaluated in combination with others, either for those persons with intolerance to usual drugs, or for TB resistance to usual combinations.


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