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Rifamycins

by Hans P. Schlecht, MD, MSc, Christopher Bruno, MD

The rifamycins are bactericidal and inhibit bacterial DNA-dependent RNA polymerase, suppressing RNA synthesis (see Table: Rifamycins).

Rifamycins

Rifabutin

Rifaximin

Rifampin

Rifapentine

Rifampin, Rifabutin, and Rifapentine

Rifampin, rifabutin, and rifapentine have similar pharmacology, antimicrobial spectra, and adverse effects.

Pharmacology

Oral absorption is good, producing wide distribution in body tissues and fluids, including CSF.

Rifampin is concentrated in polymorphonuclear granulocytes and macrophages, facilitating clearance of bacteria from abscesses. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine.

Indications

Rifampin is active against

  • Most gram-positive and some gram-negative bacteria

  • Mycobacterium sp

Resistance develops rapidly, so rifampin is rarely used alone. Rifampin is used with other antibiotics for

  • TB (see First-line drugs)

  • Atypical mycobacterial infection (rifampin is active against many nontuberculous mycobacteria, but rapidly growing mycobacteria, such as Mycobacterium fortuitum, M. chelonae, or M. abscessus, are naturally resistant)

  • Leprosy (with dapsone with or without clofazimine)

  • Staphylococcal infections, including osteomyelitis, prosthetic valve endocarditis, and infections involving foreign bodies such as a prosthetic joint (with other antistaphylococcal antibiotics)

  • Legionella infections (older data suggest better outcomes for rifampin when used with erythromycin; use of rifampin with azithromycin or a fluoroquinolone offers no advantage)

  • Pneumococcal meningitis when organisms are susceptible to rifampin (with vancomycin with or without ceftriaxone or cefotaxime for ceftriaxone- or cefotaxime-resistant organisms [MIC > 4 μg/mL]) or when expected clinical or microbiologic response is delayed

Rifampin can be used alone for prophylaxis of close contacts of patients with meningococcal or Haemophilus influenzae type b meningitis.

Rifabutin and rifampin are equally efficacious in regimens for TB in HIV-positive and HIV-negative patients.

Rifabutin is more active than rifampin against M. avium complex and is used preferentially in multidrug regimens for these infections, but otherwise, rifampin is preferred.

Rifapentine is used to treat pulmonary TB and latent TB.

Contraindications

Rifampin and rifabutin are contraindicated in patients who have had an allergic reaction to them.

Use During Pregnancy and Breastfeeding

Rifabutin is in pregnancy category B (animal studies show no risk and human evidence is incomplete, or animal studies show risk but human studies do not). Safety during breastfeeding is unknown.

Rifampin and rifapentine are in pregnancy category C (animal studies show some risk [in this case, teratogenicity], evidence in human studies is inadequate, but clinical benefit sometimes outweighs risk). The drug crosses the placenta. Still, if risk of maternal TB is moderate or high, treatment is thought to be less harmful for the fetus than untreated maternal TB and is thus recommended.

Because of potential tumorigenicity shown in animal studies, the manufacturer does not recommend use of rifampin during breastfeeding. However, the Centers for Disease Control and Prevention (CDC) does not consider rifampin a contraindication to breastfeeding; a decision to stop breastfeeding or to stop the drug should be made depending on the importance of the drug to the mother.

Adverse Effects

Adverse effects include

  • Hepatitis (most serious)

  • GI disturbances

  • CNS effects

  • Myelosuppression

Hepatitis occurs much more often when isoniazid or pyrazinamide is used concurrently with rifampin. During the first week of therapy, rifampin may cause a transient rise in unconjugated serum bilirubin, which results from competition between rifampin and bilirubin for excretion and which is not in itself an indication for interrupting treatment.

CNS effects may include headache, drowsiness, ataxia, and confusion. Rash, fever, leukopenia, hemolytic anemia, thrombocytopenia, interstitial nephritis, acute tubular necrosis, renal insufficiency, and interstitial nephritis are generally considered to be hypersensitivity reactions and occur when therapy is intermittent or when treatment is resumed after interruption of a daily dosage regimen; they are reversed when rifampin is stopped.

Less serious adverse effects are common; they include heartburn, nausea, vomiting, and diarrhea. Rifampin colors urine, saliva, sweat, sputum, and tears red-orange.

Dosing Considerations

If patients have a liver disorder, liver function tests should be done before rifampin therapy is started and every 2 to 4 wk during therapy, or an alternate drug should be used. Dose adjustments are unnecessary for renal insufficiency.

Rifampin interacts with many drugs because it is a potent inducer of hepatic cytochrome P-450 (CYP450) microsomal enzymes. Rifampin accelerates elimination and thereby may decrease the effectiveness of the following drugs: ACE inhibitors, atovaquone, barbiturates, β-blockers, Ca channel blockers, chloramphenicol, clarithromycin, oral and systemic hormone contraceptives, corticosteroids, cyclosporine, dapsone, digoxin, doxycycline, fluconazole, haloperidol, itraconazole, ketoconazole, the nonnucleoside reverse transcriptase inhibitors delavirdine and nevirapine, opioid analgesics, phenytoin, protease inhibitors, quinidine, sulfonylureas, tacrolimus, theophylline, thyroxine, tocainide, tricyclic antidepressants, voriconazole, warfarin, and zidovudine. To maintain optimum therapeutic effect of these drugs, clinicians may have to adjust the dosage when rifampin is started or stopped.

Conversely, protease inhibitors, as well as other drugs (eg, azoles, the macrolide clarithromycin, nonnucleoside reverse transcriptase inhibitors) inhibit CYP450 enzymes and increase levels of rifamycins and thus potentially increase the frequency of toxic reactions. For example, uveitis occurs more commonly when rifabutin is used with clarithromycin or azoles.

Rifaximin

Rifaximin is a derivative of rifamycin that is poorly absorbed after oral administration; 97% is recovered primarily unchanged in feces.

Rifaximin can be used for empiric treatment of traveler’s diarrhea, which is caused primarily by enterotoxigenic and enteroaggregative Escherichia coli. Rifaximin is not known to be effective for diarrhea due to enteric pathogens other than E. coli. Because rifaximin is not systemically absorbed, it should not be used to treat infectious diarrhea caused by invasive enteric bacterial pathogens (eg, salmonellae, Campylobacter sp).

The dose is 200 mg po q 8 h for 3 days in adults and children > 12 yr.

Adverse effects include nausea, vomiting, abdominal pain, and flatulence.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • PRIFTIN
  • RIFADIN, RIMACTANE
  • XIFAXAN
  • MYCOBUTIN
  • ERY-TAB, ERYTHROCIN
  • ACZONE
  • ROCEPHIN
  • ZITHROMAX
  • VANCOCIN
  • CLAFORAN
  • No US brand name
  • LANIAZID
  • NIZORAL
  • RETROVIR
  • LANOXIN
  • PERIOSTAT, VIBRAMYCIN
  • PROGRAF
  • RESCRIPTOR
  • VFEND
  • HALDOL
  • DIFLUCAN
  • NEORAL, SANDIMMUNE
  • VIRAMUNE
  • MEPRON
  • SPORANOX
  • COUMADIN
  • DILANTIN
  • BIAXIN
  • ELIXOPHYLLIN

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