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Inhibition of mRNA Synthesis

المؤلف:  Peter Chin-Hong, Elizabeth A. Joyce, Manjiree Karandikar, Mehrdad Matloubian, Luis Alberto Rubio, Brian S. Schwartz, Warren Levinson

المصدر:  Levinsons Review of Medical Microbiology & Immunology: A Guide to Clinical Infectious Diseases (2024)

الجزء والصفحة:  18th E , P75

2026-09-10

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Rifampin is used primarily for the treatment of tuberculosis in combination with other drugs and for prophylaxis in close con tact with patients with meningitis caused by either N. meningitidis or H. influenzae. It is also used in combination with other drugs in the treatment of prosthetic-valve endocarditis caused by S. epidermidis. In 2018, the FDA approved the use of oral rifampin for the treatment of traveler’s diarrhea caused by E. coli. With the exception of the short-term prophylaxis of meningitis and treatment of traveler’s diarrhea, rifampin is given in combination with other drugs because resistant mutants appear at a high rate when it is used alone.

The selective mode of action of rifampin is based on blocking mRNA synthesis by bacterial RNA polymerase without affecting the RNA polymerase of human cells. Rifampin is red, and the urine, saliva, and sweat of patients taking rifampin often turn orange; this is disturbing but harmless. Rifampin is excreted in high concentration in saliva, which accounts for its success in the prophylaxis of bacterial meningitis since the organisms are carried in the throat.

Rifabutin, a rifampin derivative with the same mode of action as rifampin, is useful in the prevention of disease caused by M. avium-intracellulare in patients with severely reduced numbers of helper T cells (e.g., acquired immunodeficiency syndrome [AIDS] patients). Note that rifabutin does not increase cytochrome P450 as much as rifampin, so rifabutin is used in human immunodeficiency virus (HIV)/AIDS patients taking protease inhibitors or non-reverse transcriptase inhibitors (NRTI).

Fidaxomicin (Dificid) inhibits the RNA polymerase of C. difficile. It is used in the treatment of pseudomembranous colitis and in preventing relapses of this disease. It specifically inhibits C. difficile and does not affect the gram-negative normal flora of the colon.