Rifabutin: a review with emphasis on its role in the prevention of disseminated Mycobacterium avium complex infection.
OBJECTIVE
To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of rifabutin.


METHODS
Pertinent literature published between 1982 and 1993 was identified via a MEDLINE search. Published proceedings of selected conferences were also reviewed.


METHODS
Selected basic science, microbiologic, and pharmacokinetic articles were evaluated. Because only limited data regarding rifabutin were available in the literature, all clinical trials involving the use of rifabutin in the prevention of Mycobacterium avium complex (MAC) infection in AIDS patients were reviewed.


RESULTS
Rifabutin is a rifamycin derivative that was approved recently for the prevention of disseminated MAC disease in patients with advanced HIV infection. The drug has in vitro and in vivo activity against gram-positive bacteria, gram-negative bacteria, and mycobacteria. Two prospective, randomized, double-blind, placebo-controlled, multicenter trials demonstrated that rifabutin decreased the progression to MAC bacteremia in AIDS patients by about 50 percent. Adverse effects that resulted in the discontinuation of rifabutin prophylaxis occurred in 16 percent of patients. Rifabutin induces hepatic enzymes to a lesser extent than does rifampin, but dosage adjustment of drugs that are known to interact with rifampin may be required.


CONCLUSIONS
Rifabutin is the only drug shown to be effective in the prevention of MAC bacteremia in AIDS patients; therefore, it should be made available as a formulary agent. It may be reasonable to delay initiation of rifabutin prophylaxis until CD4 lymphocyte counts are less than 75-50/mm3.
Pharmacy Service (119), VA Medical Center, San Francisco, CA 94121.
D S
DS
Maddix
K B
KB
Tallian
P S
PS
Mead
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D016470:Bacteremia / Q000517:prevention & control*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D015337:Multicenter Studies as Topic; D015270:Mycobacterium avium-intracellulare Infection / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D017828:Rifabutin / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012307:Risk Factors; D013045:Species Specificity
D017828:Rifabutin