Rifamycins

Agents: rifampin, rifabutin, rifapentine,  rifaximin (not used for mycobacterial disease)

The rifamycins are cornerstones of therapy for both tuberculosis and MAC. They are protein syn-thesis inhibitors that inhibit transcription of DNA to bacterial mRNA. Rifampin (or rifampicin, as it is known in European literature) is one of the two most important drugs in tuberculosis pharmacotherapy. The rifamycins are potent inducers of the cytochrome P450 system, and patients receiving them should  always be screened for drug interactions. In addition to their activity against mycobacteria, rifamycins are active against many  “typical” bacteria as well and are sometimes added to other therapies, particularly to treat difficult MRSA infections.

Spectrum

Good: Most mycobacteria

Moderate: Staphylococcus,  Acinetobacter, Enterobacteraciae

Poor: “Typical” bacteria as monotherapy, some very rare mycobacteria

Adverse Effects

Rifamycins are generally well-tolerated drugs that are most notorious for their potent CYP450-inducing effects. Their potent induction of metabolism can lead to subtherapeutic concentrations of other drugs that can manifest with devastating clinical consequences, such as loss of seizure control (anticonvulsants) or organ rejection (antirejection agents).  Rifampin characteristically colors secretions (urine,  tears, etc.) orange-red and can actually stain contact lenses, which should not be worn during rifampin therapy. Otherwise, this effect is nonpermanent and not harmful, which patients appreciate knowing. Rifamycins can also cause hepatotoxicity. Less serious side effects include rash, nausea, vomiting, and hypersensitivity (often fever).

Important Facts

• Rifampin is a drug of choice for tuberculosis,  while rifabutin is a drug of choice for MAC, al-though both drugs have activity against both pathogens. MAC infections are most common in patients with HIV, who are often taking anti-retroviral therapy that is metabolized by CYP450. Because rifabutin has somewhat fewer CYP450-inducing effects than rifampin does, it is more commonly used in MAC infections to minimize the impact of drug interactions in this population.

• Rifampin (or rifabutin) is one of the two most important drugs in the treatment of tuberculosis (the other being isoniazid). If an isolate of M.  tuberculosis is rifampin-resistant, then the likelihood of successful pharmacotherapy is lower and more complicated regimens must be used for a longer duration.

• All rifamycins induce CYP450 enzymes and can induce the metabolism of drugs through other hepatic pathways as well. Always screen for drug interactions when starting a rifamycin.

• Rifabutin induces CYP450 metabolism less potently than rifampin does, but it is still a potent inducer.

• Rifapentine is a second-line drug that is given once weekly. It shares susceptibility with rifampin and rifabutin, meaning that if an isolate is resistant to one drug, it is resistant to all of them.

• Rifaximin is a nonabsorbed rifamycin used only in the treatment or prevention of GI conditions.  It is not used for mycobacterial diseases and is listed here only for completeness.

• Rifamycins should not be used as monotherapy for treatment of active tuberculosis, but they can be used as monotherapy to treat latent tuberculosis infection. They are second-line drugs for this use.

What They’re Good For

Treatment of active tuberculosis and MAC, in com-bination with other agents; latent tuberculosis; and selected bacterial infections (most notably endocarditis of a prosthetic valve in combination with another antibiotic).

Don’t Forget!

Ensure that patients are informed that their urine and other secretions may turn orange or red. That’s a surprise that most people don’t want.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.