There are obvious shortcomings to this including the following: (a) In some cases patients have failed therapy due to non-compliance, not drug resistance; in these cases, patients unnecessarily receive toxic and expensive medications. (b) Without susceptibility tests, patients may receive inadequate regimens which result in additional acquired resistance, treatment failure, and too often, death. However, at the present time, many physicians still must employ this approach.
By contrast, guided by in vitro susceptibility results, clinicians may utilize individualized therapy. This consists of multiple drug regimens employing medications, which, preferably, have not been previously employed in that patient and are active in vitro against the patient's TB strain (1). We always initiate this re-treatment in the hospital where all doses are observed, toxicity or other adverse reactions are quickly recognized and dealt with, and absorption and other pharmokinetic parameters can be made optimal; however, Farmer and colleagues in Peru have recently reported on a very successful program of home-based care of MDR-TB (5). Assuring adequate serum concentrations is particularly critical in AIDS patients who are prone to malabsorption of TB medications. Currently available anti-TB drugs are shown in Table 3; doses and pharmokinetic data are displayed in Table 4. Clinical aspects of these drugs' usage are discussed in detail in the New England Journal of Medicine review article (1). Suggested treatment approaches to patients with various patterns to drug resistance are represented in Table 5.
Surgical Intervention
This is indicated when patients either fail to respond to medical therapy or enjoy an initial bacteriological response but are deemed likely to relapse due to the extent of resistance and/or disease. Surgery is extremely complex and should only performed by those with substantial experience. We usually wait until 3 to 4 months of intensive re-treatment before sending patients to surgery in order to reduce operative complications. Following resection, we recommend 18 to 24 months of chemotherapy to minimize the risk of relapse. Employing surgery during the decade 1984 to 1993, the overall cure rate for MDR-TB patients was 81% compared to the prior decades' 56%. And, for the patients who were selected for surgery, 57 of 60 (95%) have enjoyed sputum culture negativity. Indications and constraints are delineated in our 1990 article (6).
References:
1. Iceman M. Treatment of Multi-drug resistant tuberculosis. N Engl. J Med 1993; 784-791.
2. Pablos-Mendez A, Raviglione MC, Laszlo, A, et al. Global Surveillance for Antituberculosis-Drug Resistance. NEJM 1998, 1994-1997; Vol. 338: 1641-1649.
3. Mitchison DA, Nunn DA. Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis 1986; 133 423-430.
4. Goble M, Iseman M, Madsen L, et al. Treatment of 171 patients with pulmonary tuberculosis resistant to Isoniazid and rifampin. N Engl. J Med 1993; 328: 527-532.
5. Farmer P. Harvard University School of Medicine. Boston, MA. Personal communication.
6. Iseman M, Madsen L, Goble M, et al. Surgical intervention in the treatment of pulmonary disease caused by drug-resistant Mycobacterium tuberculosis. Am Rev Respir Dis 1990; 141: 623-625.
7. Crofton J, Chaulet P, Mahet D. Guidelines for the Management of Drug-Resistant Tuberculosis. 1997, Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland.
