Interventions for Tuberculosis Control and Elimination 2002

Rifabutin is active against a wide range of microorganisms, including
gram-negative and gram-positive bacteria, and mycobacteria. 1078,1079 In particular,
among mycobacteria, it is more active against environmental species
that are naturally resistant to rifampicin, 1080,1081 including M. avium complex.
1081-1085 While there is considerable cross-resistance with rifampicin,
it is also active against a relative small subset of M. tuberculosis strains
that have low resistance to rifampicin. 1083 However, this proportion is too
small to make it a generally useful drug in rifampicin-resistant disease. 1086
Treatment results among patients with drug-susceptible organisms are similar
to those obtained with rifampicin. 1087-1089 However, studies on early
bactericidal activity suggest that it is less active on extracellular bacilli than
rifampicin. 1090
Rifabutin is more lipid soluble than rifampicin, thus tissue penetration
is superior. 1091 It has a longer terminal half-life, and is extensively metabolized.
1091
The daily (and twice-weekly) recommended dosage of rifabutin is
5 mg/kg body weight. 897
Adverse drug events reported with rifabutin treatment are similar to
those with rifampicin treatment and include rash, hepatitis, fever, thrombocytopenia,
orange-colored body fluids, arthralgia, uveitis, and leukopenia.
897,1076 Some of these reactions may be potentiated through the interaction
with anti-retroviral protease inhibitors.
Rifabutin induces hepatic metabolism, but not as markedly as
rifampicin. 1091 It does not affect the pharmacokinetics of antiretroviral drugs
that are excreted in the urine. 1091 A number of results from interaction studies
show that rifabutin is a less potent inducer of the cytochrome P-450 family,
and thus causes fewer clinically significant interactions than rifampicin, 1092
or they are less pronounced. 281 In particular, interactions with protease
inhibitors are generally less than with rifampicin, 897,1093 and it is the rifamycin
of choice for patients receiving highly active anti-retroviral therapy.
Resistance in sub-inhibitory concentrations is less rapidly acquired than
with rifampicin. 1094 Similar to rifampicin, acquisition of resistance is frequently
accompanied by mutations in the rpoB gene. 1095 However, up to
20% of rifampicin-resistant mutants with mutations in the rpoB gene are
susceptible to rifabutin. 1096 This difference is not due to additional mechanisms
of resistance, it is just that some of the mutations selected by
rifampicin do not sufficiently modify the rpoB structure as to render this
protein resistant to rifabutin (Telenti A, personal written communication,
March 15, 2001).
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