Tuberculosis Treatment and Pathophysiology

Introduction to Tuberculosis

The Centers for Disease Control and Prevention recommends that M. tuberculosis is transmitted via aerosol droplets, and within the host, three separate subpopulations of M. tuberculosis exist, defined by their growth characteristics and location, including rapidly growing extracellular bacilli, slow-growing bacilli, and dormant bacilli 1, 2, 3

The frequency of spontaneous mutations conferring drug resistance varies by drug, with approximately 10^-6 for isoniazid and streptomycin, 10^-8 for rifampin, and 10^-5 for ethambutol, according to the MMWR Recommendations and Reports 3

The American Thoracic Society recommends that the primary goals of antituberculosis therapy are to rapidly reduce actively growing bacilli, eradicate persisting bacilli, and prevent acquisition of drug resistance, using multiple drugs simultaneously to prevent emergence of drug-resistant populations 2, 3
The standard regimen for drug-susceptible pulmonary TB is a 6-month course consisting of isoniazid, rifampin, pyrazinamide, and ethambutol, according to the American Journal of Respiratory and Critical Care Medicine 6, 2
The American Journal of Respiratory and Critical Care Medicine recommends that a 6-9 month regimen is recommended for most forms of extrapulmonary TB, with exceptions requiring longer treatment, such as tuberculous meningitis and bone/joint tuberculosis in children 4, 6, 7
The MMWR Recommendations and Reports recommends that treatment duration for HIV-infected patients with TB should be at least 9 months, with directly observed therapy (DOT) being especially important for HIV-infected patients 5, 6, 8
The American Journal of Respiratory and Critical Care Medicine recommends that paradoxical reactions are more common in HIV-infected patients and may require corticosteroid therapy, and that risk factors for drug resistance include previous TB treatment, contact with known drug-resistant TB case, and HIV infection in some settings 9, 3, 8

The American Journal of Respiratory and Critical Care Medicine recommends that dose adjustments are needed for certain drugs in patients with renal insufficiency, and close monitoring is required due to hepatotoxicity risk of INH, RIF, and PZA in patients with liver disease 6

The MMWR Recommendations and Reports recommends that failure to use multiple drugs simultaneously can lead to emergence of drug resistance, and inadequate treatment duration increases risk of relapse, according to the MMWR Recommendations and Reports 3, 1
The American Journal of Respiratory and Critical Care Medicine recommends that extrapulmonary TB may be difficult to diagnose due to limited access to specimens and lower bacterial loads, and response to treatment in extrapulmonary TB often must be judged on clinical and radiographic findings rather than bacteriological evaluation 4