Treatment Of Drugsensitive Tb

General

Streamlined yet efficacious regimens for the treatment of TB have been developed to improve compliance and cure rates. The Centers for Disease Control and Prevention (CDC) and the American Thoracic Society (ATS) currently recommend three options for the initial treatment of TB (4,22). The first, and simplest, is to begin with INH, rifampin, and pyrazinamide. The two key drugs in the regimen are INH and rifampin. Relapse rates are 0-4% with susceptible M. tuberculosis, 2-7% with INH-resistant bacteria, and up to 72% with rifampin resistance (26). The inclusion of pyrazinamide is essential for the rapid sterilization of cavities, but the ability of pyrazinamide to prevent the emergence of resistance is low. For this reason, a fourth drug (ethambutol or streptomycin) is recommended if resistance to INH in the community is >4% (27). In one study, only 3.5% of isolates were resistant to a drug in the regimen including ethambutol, and only 4.7% of isolates were resistant to a drug in the regimen including streptomycin (28). The fourth drug can be stopped as soon as the laboratory confirms that the isolate is susceptible to INH and rifampin. Pyrazinamide should be continued for 2 mo and INH and rifampin for a total of 6 mo.

The second recommended option is to treat with four drugs daily for 2 wk followed by all four drugs for another 6 wk on a twice per week schedule. If the organism is sensitive to INH and rifampin, the other drugs can be stopped and INH and rifampin con tinued for the remaining 4 mo of short-course therapy. The third option is treat with INH, rifampin, pyrazinamide, and ethambutol or streptomycin three times per week for the entire 6 mo. Recommended doses of each drug and potential side effects are listed in Tables 1 and 2.

The use of fixed-dose combinations of antituberculous drugs has been proposed as one method to prevent drug resistance (29). Rifamate™ (Hoechst Marion Roussel, Kansas City, MO) containing 150 mg of INH and 300 mg of rifampin per tablet, and Rifater™ (Hoechst Marion Roussel) containing 50 mg of INH, 120 mg of rifampin, and 300 mg of pyrazinamide per tablet are currently the only two products on the market. The idea is that patients taking fixed-dose combinations would not be able to stop a single agent without stopping therapy completely. Thus selection of organisms resistant to a single antibiotic is unlikely. However, because multiple tablets need to be ingested to achieve the necessary dose, there is the possibility that a patient may not take the full complement of pills and thus be underdosed. This might allow the emergence of resistance to all agents simultaneously.

Rifapentine (Priftin™, Hoechst Marion Roussel) has recently been marketed. This antibiotic has a half-life of >13 h, allowing it to be administered on a twice weekly or once weekly basis in place of rifampin. Patients have been treated with a regimen of INH, pyrazinamide, and ethambutol given daily plus rifapentine (600 mg) given twice weekly for 2 mo, followed by INH (900 mg) and rifapentine (600 mg) given weekly for 4 mo. The sputum conversion rate was 87% for this regimen compared to the standard rifampin-containing regimen, but relapse rates were higher (10% vs 5%, respectively) (30).

When difficulties arise with antituberculous therapy, the treatment regimens may need to be adjusted. This is difficult with fixed-dose combinations. It is easier to identify the drug responsible for adverse reactions if drugs are being administered individually. If the primary problem is drug toxicity, it is safe to change or add a single agent as long as the patient is being treated with at least two drugs to which the mycobacterium is still sensitive. It is imperative, however, never to add a single agent to a regimen where the patient is not improving or worsening clinically. Clinical failure implies that the organism is resistant to most, if not all, agents being used. If only a single new agent is added, the probability that the organism will become resistant to the new agent is high.

Considerations for Patients Coinfected with HIV

The immunosuppression due to HIV infection impairs the host response to infection with M. tuberculosis, and infection with M. tuberculosis accelerates the progression of HIV disease. Coinfection results in a higher relapse rate after treatment and a TB mortality rate that is four times that of persons not infected with HIV (31). Eleven percent of European HIV-infected patients and up to 75% of African patients with HIV infection may be coinfected with TB. In the United States, the incidence of TB in AIDS patients may be 200-800 times greater than that of the general population (32).

Treatment of TB in HIV-infected persons can be very complex for a number of reasons. First, drug resistance is more common in HIV-infected patients than in unin-fected persons. Resistance rates among HIV-infected and noninfected patients were 11.3% and 5.5% for isoniazid, 8.9% and 1.6% for rifampin, 5.1% and 1.8% for pyraz-

Table 1

Dosage Recommendations for the Initial Treatment of TB Among Children and Adults

Dosage

Table 1

Dosage Recommendations for the Initial Treatment of TB Among Children and Adults

Dosage

Drugs

Was this article helpful?

0 0
How To Win Your War Against Bronchitis

How To Win Your War Against Bronchitis

Sick And Tired Of Your Constant Cough? Is Your Bad Immune System Leading You To The Path Of Fever And Sore Chest? You Sure Have A Reason To Panic BronchitisThere Is Always A Way Out And, This Is It Finally Discover Some Of The Most Effective Tips That Can Curb Bronchitis, And Its Repeated Bouts Learn How To Keep The Chronic Cough, And Sore Chest Away Breathe Free, And Feel The Whiff Of Fresh Air, With No Hassles

Get My Free Ebook


Post a comment