e1-12: Rifamycins

In addition to its use as a primary agent in the treatment of active and latent tuberculosis, rifampin is used as an adjunct in the treatment of S aureus infections. When used as monotherapy, rifampin is associated with rapid emergence of resistance in staphylococci. However, when added to other primary antistaphylococcal agents, rifampin improves outcomes in the treatment of infected prosthetic hardware. Due to its rapid bactericidal activity, rifampin was hypothesized to be an effective adjunct in the treatment of S aureus bacteremia without hardware present. However, the addition of rifampin to standard therapy for the treatment of S aureus bacteremia does not improve outcomes, including treatment failure, recurrence, or death. Rifampin is also effective for the treatment of latent tuberculosis infection.

Rifaximin, a derivative of rifamycin, is nonabsorbable, reaches very high levels in the stool, and has a broad spectrum of antibacterial activity, including aerobic and anaerobic gram-positive and gram-negative organisms. It is approved for use in nonpregnant women and for persons aged 12 years or older to treat noninvasive traveler's diarrhea (200 mg three times daily for 3 days) but should not be used if fever or bloody diarrhea is present. Rifamycins consistently display potent in vitro activity against C difficile, and small studies suggest rifaximin is useful, particularly in the treatment of patients with recurrent disease. Other potential uses include prophylaxis of traveler's diarrhea (200 mg/day) and therapy of hepatic encephalopathy (400 mg twice daily). Rifaximin is also approved for the treatment of irritable bowel syndrome with diarrhea in adults. It is well tolerated and safe.

Rifapentine, a long-acting rifamycin, in combination with isoniazid, can be administered once-weekly for 12 weeks in the treatment of latent tuberculosis. Although previously considered the gold standard for latent tuberculosis, the World Health Organization considers 9 months of isoniazid monotherapy to be equivalent to 3 months of rifapentine with isoniazid. Even under directly observed treatment, completion of treatment is more likely with the short course of rifapentine with isoniazid compared with longer courses of isoniazid monotherapy.