Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli

Abstract

Objective: To determine the clinical manifestations of patients with human immunodeficiency virus (HIV) infection and tuberculosis caused by multiple-drug-resistant bacilli compared with those with single-drug-resistant or susceptible bacilli.

Design: Descriptive, case-control, and cohort studies.

Setting: A large urban teaching hospital.

Patients: Sixty-two patients with tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients with tuberculosis caused by single-drug-resistant or susceptible bacilli (controls).

Measurements: Characteristics of clinical presentation, radiographs, pathologic abnormalities, antituberculosis treatment, and clinical course.

Results: Twenty cases (32%) had concomitant pulmonary and extrapulmonary disease at presentation compared with 9 controls (16%; odds ratio, 2.4; 95% CI, 1.0 to 5.9). More cases had alveolar infiltrates (76%; odds ratio, 3.6; CI, 1.2 to 11.4), interstitial infiltrates with a reticular pattern (67%; odds ratio, 7.8; CI, 1.0 to 83.5), and cavitations (18%; odds ratio, 6.6; CI, 0.8 to 315.3) on initial chest radiographs compared with controls (49%, 19%, and 3%, respectively). Pathologic specimens from cases showed extensive necrosis, poor granuloma formation, marked inflammatory changes with a predominance of neutrophils, and abundant acid-fast bacilli. Twenty-five cases received two or more effective antituberculosis drugs for more than 2 months. Only 2 cases had three consecutive negative cultures for Mycobacterium tuberculosis; one patient died within 1 day of the last negative culture, and the other had positive cultures 496 days later. The remaining 23 cases had persistently or intermittently positive cultures despite therapy. The clinical course of these cases suggested overwhelming miliary tuberculosis with involvement of the lungs (77%), pleura (15%), stool (34%), meninges (13%), bone marrow (16%), blood (10%), lymph nodes (10%), and skin (8%). The median survival time was 2.1 months for cases compared with 14.6 months for controls (P = 0.001, log-rank test).

Conclusions: Tuberculosis caused by multiple-drug-resistant bacilli in patients with HIV infection is associated with widely disseminated disease, poor treatment response with an inability to eradicate the organism, and substantial mortality.