A positive PPD skin test in an asymptomatic patient with a normal chest x-ray film and negative HIV test represents latent infection with no active disease. A 6- to 9-month course of isoniazid is effective in treating this latent infection and in preventing the development of active TB. Isoniazid therapy is associated with clinical hepatitis in approximately 0.6% of treated patients (Smieja et al., 1999). An effective alternative is rifampin for 4 months. The short course of two drugs, rifampin and pyrazinamide for 2 months, is no longer recommended because of evidence of increased liver toxicity with this combination (CDC, 2001). Treatment of positive PPD latent infection is indicated even in patients with prior history of BCG vaccination and is also effective in patients co-infected with HIV (Wilkinson et al., 1998).

Treatment of active pulmonary TB requires a multidrug regimen for 6 to 12 months. For uncomplicated pulmonary TB, a short-course protocol of four drugs (isoniazid, rifampin, pyrazinamide, ethambutol) for the first 2 months and two drugs (isoniazid, rifampin) for the next 4 months is effective. Treatment with intermittent therapy 2 days per week has been less effective than daily therapy in RCTs (Mwandumba and Squire, 2001). Repeat cultures should be obtained after 2 months of treatment, when 80% of patients have negative cultures. Cavitary lesions, or persistent positive cultures after 2 months of therapy, are indications for an extended 9-month course of treatment. New drugs entering the pipeline of clinical trials include long-acting rifamycins and fluoroquinolones.

Directly observed therapy (DOT) is indicated for patients with specific risk factors for treatment failure caused by non-compliance, but RCTs in a variety of settings have not clearly demonstrated benefit over traditional public health strategies (Volmink and Garner, 2003). Enhanced DOT appears to be more effective. Box 18-6 lists strategies of social supports, barrier reduction, compliance monitoring, and incentives that can be blended in a broad-based strategy to ensure treatment compliance and cure (ATS, CDC, IDSA, 2003). WHO reports an 82% success rate for TB treatment worldwide, although the prevalence of multidrug-resistant TB is increasing.

Treatment of patients who have positive PPD and x-ray evidence of TB but negative sputum smears depends on the level of clinical suspicion for active TB. When suspicion is high, multidrug therapy should be initiated pending culture results. If cultures come back negative but the patient shows clinical or radiographic signs of improvement after 2 months of treatment, the patient is assumed to have culture-negative TB, and treatment should be completed using isoniazid and rifampin. If culture remains negative and there is no sign of clinical or radiographic improvement, treatment may be

Box 18-6 Broad-Based Strategy to Ensure Tuberculosis Treatment Adherence and Cure

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