Author: Brian Holtry

Rifapentine has an antibacterial spectrum of activity similar to that of rifampin; however, on a molar basis, rifapentine and its active 25-desacetyl metabolite generally are more active than rifampin against Mycobacterium tuberculosis and more active than rifampin but less active than rifabutin against M. avium complex (MAC). The clinical relevance of activity of rifapentine against other mycobacterial species has not been established.

Rifapentine is used in conjunction with other antituberculosis agents in the treatment of clinical tuberculosis. The American Thoracic Society (ATS), US Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) currently recommend several possible multiple-drug regimens for the treatment of culture-positive pulmonary tuberculosis.

In addition, HIV protease inhibitors and some NNRTIs (e.g., delavirdine) reduce the metabolism of rifamycins, leading to increased plasma concentrations of rifamycins and an increased risk of toxicity. The potential for alterations in the plasma concentrations of antimycobacterial agent(s) and/or antiretroviral agent(s) must be considered when antimycobacterial agents are indicated for the management of latent or active tuberculosis or the prophylaxis or treatment of Mycobacterium avium complex (MAC) infections in HIV-infected patients who are receiving or are being considered for antiretroviral therapy. Although pharmacokinetic data and clinical experience are limited, some experts state that concomitant use of ritonavir (with or without saquinavir) and usual dosages of rifampin for the treatment of tuberculosis (600 mg daily or 2 or 3 times weekly) is a possibility. These experts state that rifampin can be used for the treatment of active tuberculosis in patients receiving an antiretroviral regimen that includes ritonavir and one or more nucleoside reverse transcriptase inhibitors.

The most frequent adverse effects of rifampin are GI disturbances, which include heartburn, epigastric distress, nausea, vomiting, anorexia, abdominal cramps, flatulence, and diarrhea. Rarely, adverse GI effects may be severe enough to require discontinuance of the drug.

Rifampin usually is administered orally. When oral therapy is not feasible, the drug may be given by IV infusion. Rifampin should not be administered IM or subcutaneously since local irritation and inflammation can occur. Rifampin should be given orally either 1 hour before or 2 hours after a meal with a full glass of water to ensure maximum absorption.

Rifampin is used in conjunction with other antituberculosis agents for the treatment of clinical tuberculosis.

Prevention of disseminated MAC disease is an important goal in the management of patients with HIV infection and low helper/inducer (CD4+, T4+) T-cell counts because of the frequency with which the disease occurs in such patients and its associated morbidity. Current evidence indicates that MAC causes disseminated disease in a substantial proportion of HIV-infected patients and that prophylaxis with rifabutin, alone or combined with azithromycin, can reduce substantially the frequency of M. avium complex bacteremia and ameliorate clinical manifestations of the disease in patients with AIDS.

Rifabutin, a semisynthetic spiropiperidyl derivative of rifamycin S, is an ansamycin antibiotic. The drug is active in vitro and in vivo against Mycobacterium avium complex (MAC), including isolates obtained from patients with acquired immunodeficiency syndrome (AIDS).

Rifabutin is administered orally. Administration of rifabutin with a high-fat meal decreases the rate but not the extent of absorption. Therefore, the drug generally can be given orally without regard to meals.

Pyrazinamide, a derivative of niacinamide, is a synthetic antituberculosis agent. Pyrazinamide is used in conjunction with other antituberculosis agents in the treatment of clinical tuberculosis.