Author: Brian Holtry

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.

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.

Isoniazid usually is administered orally. The drug may be given by IM injection when oral therapy is not possible. The fixed-combination preparation containing isoniazid and rifampin (Rifamate®) and the fixed-combination preparation containing isoniazid, rifampin, and pyrazinamide (Rifater®) should be given either 1 hour before or 2 hours after a meal; the manufacturer states that Rifater® should be given with a full glass of water.

Peripheral neuritis, usually preceded by paresthesia of the feet and hands, is the most common adverse effect of isoniazid and occurs most frequently in malnourished patients and those predisposed to neuritis (e.g., alcoholics, diabetics). Rarely, other adverse nervous system effects have also occurred including seizures, toxic encephalopathy, muscle twitching, ataxia, stupor, tinnitus, euphoria, memory impairment, separation of ideas and reality, loss of self-control, dizziness, and toxic psychosis. Neurotoxic effects may be prevented or relieved by the administration of 10-50 mg of pyridoxine hydrochloride daily during isoniazid therapy, and pyridoxine should be administered in malnourished patients, pregnant women, and those predisposed to neuritis (e.g., HIV-infected individuals).

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

Cycloserine, a structural analog of the amino acid d-alanine, is an antituberculosis antibiotic. Cycloserine is used in conjunction with other antituberculosis agents in the treatment of clinical tuberculosis.