Review Question - QID 100862

The drug described in the question stem is rifampin, an antibiotic used in the treatment of TB and leprosy. Rifampin is used as monotherapy in the case of post-exposure prophylaxis for Neisseria meningitidis.

Rifampin inhibits the DNA-dependent RNA polymerase of Mycobacterium. When used alone, bacteria quickly acquire resistance to rifampin via spontaneous mutations of RNA polymerase, necessitating the drug's use as part of combination therapy as in treatment of tuberculosis. Following exposure to N. meningitidis, however, rifampin alone can prevent active disease as well as the development of a carrier state. Recall that rifampin is an inducer of CYP450.

Kimmel reviews the prevention of N. meningitidis infection, which has an incidence of invasive disease in the US of 1/100,000 persons, with the highest incidence and case-fatality rate seen among adolescents. As a result, vaccination against N. meningitidis is recommended for adolescents and dorm inhabitants. As the disease can be rapidly fatal, household and other close contacts of the affected should receive prophylaxis with rifampin, ciprofloxacin, or ceftriaxone.

Fraser et al. conducted a meta-analysis of rifampin's use in prevention of meningococcal infections. They noted that rifampin performed the best at eliminating nasopharyngeal carrier status of N. meningitidis, but that resistance to rifampin frequently developed. No RCTs including rifampin or placebo showed evidence of secondary transmission of meningococcal disease, so efficacy could not be directly assessed.

Illustration A shows the mechanism of action of several anti-tuberculosis drugs.
Illustration B shows orange discoloration of urine in a patient taking rifampin. Sweat and tears may also be orangeish-red in color and can permanently stain soft contact lenses.

Incorrect answers:
Answer 1: MAC is treated with a macrolide + ethambutol.
Answer 2: MRSA endocarditis can be treated with vancomycin + rifampin.
Answer 4: Brucellosis should not be treated with rifampin monotherapy die to high risk of resistance. It can be used as rifampin+ streptomycin or ciprofloxacin.
Answer 5: Rifampin is appropriate to use as monotherapy for N. meningitidis prophylaxis.