Infection caused by Mycobacterium tuberculosis.
OBJECTIVE
To update readers on the clinical management of infections caused by Mycobacterium tuberculosis, to provide a general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease, and to provide several aspects of the treatment of the disease, including historical perspective, current approaches, and research opportunities for the future.


METHODS
The current medical literature, including abstracts presented at recent international meetings, is reviewed. References were identified through MEDLINE, MEDLARS II, Current Contents, and published meeting abstracts.


METHODS
Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of tuberculosis are cited. Specific attention has been focused on the clinical management of patients with noncontagious infection and potentially contagious active disease (TB) caused by M. tuberculosis.


METHODS
Information contributing to the discussion of the topics selected by the authors is reviewed. Data supporting and disputing specific conclusions are presented.


RESULTS
The incidence of TB is increasing in the US, despite the fact that available technologies are capable of controlling the vast majority of existing cases. Fueling the fire is the problem of coinfection with HIV and M. tuberculosis. Very few drugs are available for the treatment of TB, and few of these approach the potency of isoniazid and rifampin. Preventive therapy of patients exposed to multiple-drug-resistant M. tuberculosis (MDR-TB) is controversial and of unknown efficacy. Treatment of active disease caused by MDR-TB requires up to four times longer, is associated with increased toxicity, and is far less successful than the treatment of drug-susceptible TB. Strategies for the management of such cases are presented. The rising incidence of TB in the US reflects a breakdown in the healthcare systems responsible for controlling the disease, which reflects the past budgetary reductions. Although TB control is one of the most cost-effective public health strategies, funding has been cut repeatedly despite the fact that TB was never eliminated. This has helped to produce the current crisis, including the spread of MDR-TB in many urban areas. The elimination of TB will now take decades longer, cost hundreds of millions of dollars more, and result in vastly higher morbidity and mortality rates than would have occurred with timely, adequate measures.


CONCLUSIONS
Tremendous effort and far more funding will be required to eliminate TB in the US. The selection of drug therapy must be based on the susceptibility data for each isolate. Multiple-drug therapy must be continued for 6 to > or = 24 months, and patient adherence to prescribed regimens must be verified in all cases of TB. Significant antimycobacterial drug malabsorption has been documented in AIDS patients with TB, and may result in treatment failure. New agents are needed to improve the clinical outcome in patients with MDR-TB.
Peloquin
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Infectious Disease Pharmacokinetics Laboratory (IDPL), National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Berning
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D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016503:Drug Delivery Systems; D024841:Fluoroquinolones; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D012294:Rifamycins / Q000009:adverse effects / Q000627:therapeutic use; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000635:transmission; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000635:transmission
D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D024841:Fluoroquinolones; D012294:Rifamycins