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Objective: To determine, among a group of patients with multidrug-resistant pulmonary tuberculosis, whether there had been management practices that deviated from established guidelines, and whether these decisions were associated with the acquisition of multidrug resistance and adverse medical sequelae.Design: Case series.Setting: Referral center.Patients: All patients with pulmonary tuberculosis admitted to the National Jewish Center for Immunology and Respiratory Medicine in 1989 through 1990.Interventions: The records of all patients referred to this institution for the treatment of tuberculosis in 1989 through 1990 were reviewed to ascertain the nature of management decisions that might have been associated with the acquisition of drug resistance.Main Outcome Measures: Standards of practice as defined by the American Thoracic Society, the Centers for Disease Control and Prevention, and the American College of Chest Physicians were compared with these management decisions to determine whether "errors" had been made, resulting in treatment failure and the development of acquired drug resistance.Results: Among the 35 study patients, errors were detected in the management decisions in 28; there was an average of 3.93 errors per patient. The most common errors were the addition of a single drug to a failing regimen, failure to identify preexisting or acquired drug resistance, initiation of an inadequate primary regimen, failure to identify and address noncompliance, and inappropriate isoniazid preventive therapy. The multidrug resistance acquired through the errors resulted in prolonged hospitalizations, treatment with more toxic drugs, and high-risk resectional surgery. The costs for this "salvage therapy" were extraordinary, averaging $180,000 per patient.Conclusions: Aggressive professional education, tighter control on the provisions of care for tuberculosis patients, and the committing of additional resources to tuberculosis control programs are vital in improving the care of tuberculosis patients and limiting the development of acquired drug resistance. [ABSTRACT FROM AUTHOR]

The major historical landmarks of tuberculosis (TB) therapy include: the discovery of effective medications (streptomycin and para-aminosalicylic acid) in 1944; the revelation of "triple therapy" (streptomycin, para-aminosalicylic acid and isoniazid) in 1952, which assured cure; recognition in the 1970s that isoniazid and rifampin could reduce the duration of treatment from 18 to 9 months; and the observation in the 1980s that adding pyrazinamide to these drugs allowed cures in only 6 months. To combat noncompliance, intermittent regimens, twice or thrice weekly, have been proven to cure even far-advanced TB in as few as 62-78 encounters over 26 weeks. However, these regimens are not sufficiently short or convenient to facilitate effective treatment in resource-poor countries. Therefore, drug-resistant strains have emerged to threaten TB control in various areas of the world, including India, China, Russia and the former Soviet Union. For these reasons, it is vital that new medications are developed to shorten the duration of therapy, increase the dosing interval of intermittent regimens and replace agents lost to resistance. Other special considerations include identifying optimal therapy for persons with acquired immune deficiency syndrome, particularly noting the problems of drug/drug interactions for those receiving antiretroviral treatment. Finally, the Alchemist's Dream of tuberculosis should be pursued: modulating the immune response to shorten treatment and/or overcome drug resistance.

The diagnosis of tuberculosis (TB) principally rests on the sputum examination and culture. However, the sensitivity of sputum smear for acid-fast bacteria is only approximately 50% and sputum culture has a relatively long turnaround time. As a result, a number of studies have been conducted in an attempt to find a rapid and accurate diagnostic test for TB. They include serological assays against various mycobacterial antigens. Here we review the merits and deficiencies of the serological tests for TB. In general, serological assays have a high negative predictive value, making them potentially useful as a screening test to rule out active TB although in HIV-positive individuals, low sensitivity and low negative predictive value compromises the accuracy of the seroassays in this group of individuals. In populations where the prevalence of latent TB infection is high, the relatively low positive predictive value of the tests reduces their specificity for active TB. Furthermore, the higher costs and greater training required in performing these tests makes it important that future studies also assess whether their use affects patient outcomes in management of TB., (Copyright 2000 Harcourt Publishers Ltd.)

Tuberculous empyema represents a chronic, active infection of the pleural space that contains a large number of tubercle bacilli. It is rare compared with tuberculous pleural effusions that result from an exaggerated inflammatory response to a localized paucibacillary pleural infection with tuberculosis. The inflammatory process may be present for years with a paucity of clinical symptoms. Patients often come to clinical attention at the time of a routine chest radiograph or after the development of bronchopleural fistula or empyema necessitatis. The diagnosis of tuberculous empyema is suspected on computed tomography imaging by finding a thick, calcific pleural rind and rib thickening surrounding loculated pleural fluid. The pleural fluid is grossly purulent and smear positive for acid-fast bacilli. Treatment consists of pleural space drainage and antituberculous chemotherapy. Problematic treatment issues include the inability to re-expand the trapped lung and difficulty in achieving therapeutic drug levels in pleural fluid, which can lead to drug resistance. Surgery, which is often challenging, should be undertaken by experienced thoracic surgeons.

Drug-resistant tuberculosis (TB) originally is the product of inadequate therapy; this may entail noncompliance with treatment, interrupted drug supplies, or inappropriate prescription. Patients may sequentially acquire resistance to several drugs through repetition of this process. Loss of activity of the major drugs greatly compromises the treatment process; most problematic is resistance to both isoniazid and rifampicin, so-called 'multidrug-resistant tuberculosis' (MDR-TB). Recent evidence indicates that MDR-TB is being transmitted to others, and particularly to persons with HIV infection/AIDS. Other situations in which epidemic spread of MDR-TB occurs include hospitals and prisons. In several areas of the world, ominous levels of MDR-TB have been identified in a recent WHO survey. Treatment of MDR-TB entails the use of poorly tolerated, second-line medications that are often toxic, and the duration of treatment must be extended to the range of two years. Resectional surgery may be required to effect cures in patients with advanced disease in which most of the first-line agents have been lost to resistance.

Drug-resistant tuberculosis fundamentally reflects inadequate chemotherapy. To prevent increases in the prevalence of resistance, physician education and more structured treatment programs are needed. In one recent series, 80% of patients with multidrug-resistant tuberculosis (MDR-TB) had been previously managed with clear breaches of standard practice. These errors included adding a single drug to a failing regimen, failing to identify initial or acquired resistance, using an inadequate regimen, and not recognizing (and coping with) non-adherence to therapy. Both medical and surgical management should be considered in optimizing treatment of patients with MDR-TB. Optimal treatment strategies for MDR-TB are outlined in this paper. The use of susceptibility testing is strongly advised, but in situations where such laboratory services are not available, empirical management regimens are discussed.