The rifamycins are “accessory” antibiotics. Just as a stylish purse or sparkling necklace is used to adorn a dress, these antimicrobial agents are added to traditional treatment wardrobes that require a little accentuation for the optimal effect. The rifamycins consist of rifampin (also called rifampicin), rifabutin, rifapentine, and rifaximin (Table 1). Each has a similar structure that includes an aromatic nucleus linked on both ends by an aliphatic “handle” (Figure 1).
Rifamycins act by inhibiting bacterial RNA polymerase. They nestle deep into the DNA/RNA tunnel of this enzyme and, once lodged in this position, sterically block elongation of the nascent mRNA molecule. Resistance develops relatively easily and can result from one of several single mutations in the bacterial gene that encodes RNA polymerase. These mutations each change only a single amino acid at the site where the rifamycins bind to RNA polymerase but are sufficient to prevent this binding. Because single mutations are sufficient to lead to resistance, rifamycins are usually used in combination with other agents to prevent the emergence of resistant strains.
Many of the rifamycins are frequently used in combination regimens for the treatment of mycobacterial infections (Table 2). Of the rifamycins, rifampin has been used along with other antibiotics to treat staphylococcal infections. Rifampin is also effective as monotherapy for prophylaxis against Neisseria meningitidis and Haemophilus influenzae. The use of rifampin alone in prophylaxis is justified by the fact that, usually, very few bacteria are present in the absence of overt disease, thus minimizing the chance that a rifampin-resistance mutation will spontaneously occur.
Rifampin is the oldest and most widely used of the rifamycins. It is also the most potent inducer of the cytochrome P-450 system.
Rifabutin is favored over rifampin in individuals who are simultaneously being treated for tuberculosis and HIV infection because it inhibits the cytochrome P-450 system to a lesser degree than rifampin or rifapentine and thus can be more easily administered along with the many antiretroviral agents that also interact with this system.
Rifapentine has a long serum half-life, which has led to its use in once-weekly regimens for immunocompetent patients with tuberculosis.
Rifaximin is a poorly absorbed rifamycin that is used for the treatment of travelers’ diarrhea. Because it is not systemically absorbed, it has limited activity against invasive bacteria, such as Salmonella and Campylobacter spp.
The rifamycins are potent inducers of the cytochrome P-450 system. Thus, they may dramatically affect the levels of other drugs metabolized by this system. Rifamycins also commonly cause gastrointestinal complaints such as nausea, vomiting, and diarrhea and have been associated with hepatitis. Skin rashes and hematologic abnormalities may also occur. Of note, rifampin causes an orange-red discoloration of tears, urine, and other body fluids, which can lead to patient anxiety and the staining of contact lenses. Rifabutin has been associated with uveitis.
The name rifamycin was derived from the French movie Rififi, which was popular at the time these agents were discovered.
Sensi P. History of the development of rifampin. Rev Infect Dis. 1983;5(suppl 3):S402–S406.
The rifamycins are used primarily as components of multidrug regimens for mycobacterial infections and some staphylococcal infections. The ease with which bacteria develop resistance to these agents precludes their use as monotherapy in active disease.
- Rifampin binds bacterial __________________ and inhibits synthesis of __________________.
- Rifampin is used primarily in the treatment of diseases caused by __________________ and __________________.
- The rifamycins are usually used in conjunction with other antimicrobial agents because __________________ to rifamycins develops during monotherapy.
- RNA polymerase; mRNA
- mycobacteria, staphylococci
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