TB Treatment Evolves
Over the past 50 years, and without any significant advances in the past 30 years, a number of fairly reliable medicines have been developed that effectively treat tuberculosis -- as long as they are consistently and correctly taken. But simply knowing that there are drugs to treat TB is not enough, and much recent treatment research has focused on understanding the infrastructure and conditions that must be present to assure that courses of therapy are completed without interruption.
The Infectious Disease Society of America (IDSA), in association with the American Thoracic Society and the CDC has recently published updated guidelines for treating TB. The guidelines not only stress a providers responsibility to prescribe appropriate regimens but also to assure that they are completed successfully. Directly observed therapy (DOT), which entails actually watching the patient swallow the mediation, is strongly recommended. Increasingly, this demands that providers embrace patient-centered case management to assure treatment adherence; it is not acceptable to simply prescribe drugs and send a patient home, or even to demand that patients show up at a prescribed time and place to take their pills. "Treatment of patients with tuberculosis is most successful within a comprehensive framework that addresses both clinical and social issues of relevance to the patient." Enhanced DOT may now include arranging for "social service support, treatment incentives and enablers, housing assistance, referral for treatment of substance abuse, and coordination of tuberculosis services with those of other providers." Studies have reported 91 percent treatment completion when enhanced DOT is used compared to 86 percent for DOT and 61 percent for unsupervised therapy. Adherence is measured by counting doses taken, and a complete course is accounted for down to the last pill. To do less has proven to yield suboptimal results.
In clinical trials, a trade-off was seen between duration of treatment and adherence. While a 9-month course of treatment was proven effective, gains were undermined by poor adherence. It has always been a problem for TB treatment that patients will stop taking their drugs after symptoms resolve, well before the TB organism has been eradicated. Better adherence -- and better overall outcomes -- have been demonstrated by using a 6-month course of treatment that is strictly adhered to, hence the emphasis on DOT and dose counting.
Treatment is generally planned in two stages, a first intensive stage that may last two months, and, depending on the results of sputum culture test, a second phase that may last from 4 to 7 months. For adults with previously untreated TB, the initial two-month course of treatment will use a four-drug regimen of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) given daily for at least the first two weeks. Modifications may be made depending on drug susceptibility results. If TB therapy is given at the same time that certain anti-HIV drugs are being taken, rifabutin may be substituted for rifampin to avoid potential drug interactions.
For people without HIV who respond to the initial stage, the continuation phase may be as simple as once-weekly DOT to complete the six months. But regimens for people with HIV are more stringent, because their response to TB therapy is often less certain, and daily therapy, or thrice weekly at a minimum, is continued throughout the second phase.
Many of the TB drugs can cause hepatitis, which may pose special problems for patients with preexisting viral hepatitis or for persons with HIV taking antiretroviral drugs such as nevirapine that can cause hepatic toxicity. In general, the guidelines recommend toughing it out, giving precedence to finishing the course of therapy. In some cases, regimen modifications can be made, such as removing one of the liver toxic TB drugs while extending the duration of therapy. In all cases, frequent and careful monitoring should be performed to detect drug- induced liver injury.
TB Treatment in Resource-Poor Settings
The Guidelines discussed above are designed for the U.S. and appropriate for a setting with a low incidence of TB, a public health commitment to TB elimination, and the resources to accomplish this through comprehensive case management. But, what is appropriate in regions where TB is epidemic and these resources are not present? Given that most new TB cases in the U.S. occur in foreign-born individuals, the world TB problem is a persistent factor in any plan to eliminate TB domestically. The World Health Organization has developed guidelines for countries without recourse to sophisticated drug susceptibility testing and exotic backup drugs. While there are some difference in available drugs and recommended regimens, the underlying goals are the same: to assure treatment adherence and completion of the course of therapy. The strategy WHO offers to accomplish this is based on the familiar DOT, but within a national case management context called DOTS, for directly observed therapy, short course. The principles of DOTS are: "1) government commitment to sustained tuberculosis control activities, 2) case detection by sputum smear microscopy among symptomatic patients self-reporting to health services, 3) a standardized treatment regimen of 6 to 8 months for at least all confirmed sputum smear-positive cases, with DOT for at least the initial 2 months, 4) a regular, uninterrupted supply of all essential antituberculosis drugs, and 5) a standardized recording and reporting system that enables assessment of treatment results for each patient and of the tuberculosis control program overall."
CDC. Recommendations and reports: Treatment of tuberculosis. MMWR, June 20, 2003/52(RR11);1-77. www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm
This article was provided by Gay Men's Health Crisis. It is a part of the publication GMHC Treatment Issues. Visit GMHC's website to find out more about their activities, publications and services.