Faculty Bibliography

Tools for effective TB control have been available for years. Case finding, active medications, case management and directly observed therapy are the foundations for the management of TB. The current TB epidemic, centered in resource-limited settings is fueled by the HIV-1 epidemic. Lack of ability to diagnose and treat drug-resistant TB has led to development of more extensive patterns of resistance. Among the currently available drugs, there is reason to hope that rifamycins paired with fluoroquinolones will lead to shorter treatment regimens for drug-susceptible TB. As the result of novel public-private collaborations and investments of resources, new drugs are being developed. These include TMC207, already shown to have activity early in the treatment of multidrug-resistant TB and others that are likely to be active against persistor organisms, and have the prospect to dramatically shorten treatment courses for active and latent TB. Given that these drugs have novel mechanisms of action, combinations have the prospect to be highly active even against multidrug-resistant organisms

The immunodominance of Mycobacterium tuberculosis proteins malate synthase (MS) and MPT51 has been demonstrated in case-control studies with patients from countries in which tuberculosis (TB) is endemic. The value of these antigens for the serodiagnosis of TB now is evaluated in a cross-sectional study of pulmonary TB suspects in the United States diagnosed to have TB, HIV-associated TB, or other respiratory diseases (ORD). Serum antibody reactivity to recombinant purified MS and MPT51 was determined by enzyme-linked immunosorbent assays (ELISAs) of samples from TB suspects and well-characterized control groups. TB suspects were diagnosed with TB (n = 87; 49% sputum microscopy negative, 20% HIV(+)) or ORD (n = 63; 58% HIV(+)). Antibody reactivity to MS and MPT51 was significantly higher in U.S. HIV(+)/TB samples than in HIV(-)/TB samples (P < 0.001), and it was significantly higher in both TB groups than in control groups with latent TB infection (P < 0.001). Antibody reactivity to both antigens was higher in U.S. HIV(+)/TB samples than in HIV(+)/ORD samples (P = 0.052 for MS, P = 0.001 for MPT51) but not significantly different between HIV(-)/TB and HIV(-)/ORD. Among U.S. HIV(+) TB suspects, a positive anti-MPT51 antibody response was strongly and significantly associated with TB (odds ratio, 11.0; 95% confidence interval, 2.3 to 51.2; P = 0.002). These findings have implications for the adjunctive use of TB serodiagnosis with these antigens in HIV(+) subjects

OBJECTIVE: To determine whether linezolid is safe and well tolerated in the treatment of extensively drug-resistant tuberculosis (XDR-TB). MATERIALS AND METHODS: The was conducted in a specialized tuberculosis ward for multidrug-resistant tuberculosis (MDR-TB) on the Chest Service of Bellevue Hospital Center, which is a 768-bed public hospital in New York City. Seven patients with confirmed MDR-TB or XDR-TB who were still culture positive despite appropriate directly observed therapy were treated with a regimen containing linezolid and at least one other active agent. RESULTS: The linezolid-containing regimen led to sustained negative conversion of sputum cultures and radiographic improvement in all patients. Long-term therapy (longest duration of therapy, 28 months) was well tolerated in most patients. Neutropenia developed in three patients, but was reversible, and peripheral neuropathy developed in two patients. CONCLUSIONS: Linezolid remains a promising possible addition to our therapeutic armamentarium against XDR-TB. Linezolid is associated with side effects that can be adequately managed. Further studies to define the mechanism of action and optimum dose should be performed

OBJECTIVE: To identify the contamination source of a cluster of eight positive Mycobacterium tuberculosis isolates from one laboratory session. METHODS: Spoligotyping was performed on M. tuberculosis isolates processed during one laboratory session. Laboratory and sputum induction protocols and records were reviewed. Sputum induction staff were interviewed. An environmental assessment of the sputum induction booth was performed. RESULTS: Spoligotyping identified a unique strain of susceptible M. tuberculosis from five induced sputa collected at Clinic A on the same day. Three specimens processed concurrently from other clinics had spoligotypes different from each other and from the cluster strain. A laboratory investigation revealed no procedural lapses. Sputum induction records from Clinic A indicated that patient 1 in the sputum induction booth had prior culture-confirmed tuberculosis. Patient 2 had a history of a drug-resistant strain. Patient 3 had completed tuberculosis treatment, with positive cultures 7 months earlier. Patients 4 and 5 were new to the clinic and had no subsequent positive M. tuberculosis specimens. The sputum induction booth was working within normal parameters. Sputum induction that day was overseen by a new employee with limited training and no supervision. A review of the sputum induction protocol identified ambiguity regarding care of the ultrasonic nebulizer between patients, which may have led to reuse of the discarded nebulizer solution from patient 1. CONCLUSIONS: A break in the sputum induction protocol may have contributed to contamination of patient specimens. Sputum induction is complicated, mandating adequate staff training and supervision and patient preparation. Spoligotyping identified a potential source of M. tuberculosis contamination

SETTING: Bellevue Hospital, a large public hospital in New York City. OBJECTIVE: To discern the clinical characteristics of spinal tuberculosis (Pott's disease) in patients with the human immunodeficiency virus (HIV). DESIGN: Review of all cases of spinal tuberculosis seen at the hospital from 1988 to 1995, with comparison of HIV-positive and HIV-negative cases. Chart reviews for all cases were performed and information regarding signs and symptoms, neurological findings, laboratory and radiographic data, medical and surgical treatment and eventual outcome were recorded. RESULTS: We collected 26 cases of tuberculosis of the spine between July 1988 and June 1995. Seven of our 26 patients (27%) were HIV seropositive. Six of these were PPD+ on presentation. When compared with HIV-negative patients, those with HIV and spinal tuberculosis had similar clinical presentations; most patients had a diagnosis made with percutaneous needle aspiration biopsy of clinically involved areas, and open procedures added little diagnostic information. Most were treated without surgery, and response to antituberculosis therapy was uniformly good. CONCLUSION: We conclude that clinical presentations of spinal tuberculosis are similar in HIV-positive and -negative patients, and good outcomes can be expected with regard to mycobacterial disease