Pharmacology of the antimycobacterial drugs.

The management of MDR-TB requires that the clinician become familiar with the "second-line" antimycobacterial agents. These drugs are generally less potent and frequently more toxic than isoniazid and rifampin. Because they are less active, innovative dosing schedules may allow us to take advantage of the few strengths that they possess. This approach will require further research into the dose-response relationships for each agent. Based on our current knowledge of these drugs, practical guidelines for their use have been described. These guidelines include the gradual escalation of the oral doses of PAS, cycloserine, and ethionamide over several days, and the intravenous administration of streptomycin and capreomycin. Both ciprofloxacin and ofloxacin may be used for the treatment of MDR-TB, but data from clinical trials are currently lacking. Finally, because patients with AIDS appear to develop antimycobacterial drug malabsorption over the course of their HIV infection, therapeutic drug monitoring can be used to verify drug absorption in the individual patient. This approach may improve therapy for that patient and prevent the selection of additional drug resistance.