Several semisynthetic derivatives (rifamycin SV, rifampin [rifampicin], rifamide) of natural rifamycins have been used as extended-spectrum antimicrobials. Rifamycins interfere with the synthesis of RNA in microorganisms via binding to subunits of sensitive DNA-dependent RNA polymerase. They are active against gram-positive organisms, some mycobacteria, a few strains of gram-negative bacteria (mostly cocci; bacilli are more resistant), some anaerobes, and chlamydiae. Rifampin is active against most strains of methicillin-resistant Staphylococcus pseudintermedius (MRSP); however, rapid resistance develops even when rifampin is administered in combination with other antimicrobials. At high concentrations, they are also active against several viruses.
Fungal and yeast infections resistant to rifampin alone often respond when a rifamycin is added to an antifungal agent (eg, amphotericin B). Resistance to rifamycins may develop rapidly as a 1-step process. For this reason, they should be administered in combination with other antimicrobials, such as penicillins, erythromycin, miconazole, and amphotericin B.
The primary use of the rifamycins in people has been to treat tuberculosis. Rifampin has been used in foals to control Rhodococcus equi pneumonia in combination with macrolides; however, this combination has come under scrutiny ( see Interactions Interactions The macrolide antimicrobials typically have a large lactone ring in their structure and are much more effective against gram-positive than gram-negative bacteria. They are also active against... read more ). Because rifamycins penetrate tissues and cells to a substantial degree, they are particularly effective against intracellular organisms. Rifampin is readily but incompletely (~40%) absorbed from the GI tract, and plasma concentrations peak within 2–4 hours. Concurrent feeding may decrease or delay absorption.
Rifampin may also be administered IM or IV. Approximately 75%–80% of rifampin is bound to plasma proteins. It is widely distributed in body tissues and fluids because of its high lipid solubility. Rifampin is biotransformed to several metabolites, some of which are active, and is primarily excreted in bile (used for cholangitis in people) and to a lesser degree in urine. Enterohepatic cycling of the parent drug and its main metabolite (desacetylrifampin) commonly occurs.
The elimination half-life of rifampin is dose dependent: in horses, it is ~6 hours; in dogs, ~8 hours. The plasma half-life progressively shortens by ~40% during the first 2 weeks of treatment because of the induction of hepatic microsomal enzymes; conversely, it is increased with hepatic dysfunction. Use of rifampin may affect the elimination of other hepatically metabolized drugs (eg, barbiturates).
Rifampin is usually well tolerated and produces few adverse effects. Gastrointestinal disturbances and abnormalities in liver function (icterus) have been reported in people. Mild elevations in serum alkaline phosphatase activity are common with treatment. Hypersensitivity reactions can also result from rifampin administration, and renal failure is a possible consequence when intermittent dosage schedules are followed. Partial, reversible immunosuppression of lymphocytes develops. Urine, feces, saliva, sputum, sweat, and tears are often colored red-orange by rifampin and its metabolites. In horses, CNS depression after IV administration and temporary inappetence are seen.
The dosage for rifampin is 5–10 mg/kg, PO, every 12 to 24 hours in horses and 5–10 mg/kg, PO, every 24 hours in dogs and cats. Rifampin has been associated with formation of hepatic tumors in female mice. As any residue of a known carcinogen in animal products for human consumption is considered a violation of the Food, Drug and Cosmetic Act, the USP Veterinary Medicine Advisory Panel has concluded that rifampin should not be administered to animals intended for production of products for human consumption.