Rifampin

Rifampin: Overview

Rifampin (also spelled Rifampicin) is a powerful bactericidal antibiotic from the rifamycin class, primarily used in combination therapies for treating Mycobacterial infections like tuberculosis (TB), leprosy, and certain bacterial infections. It plays a crucial role in preventing bacterial resistance, especially in serious infections.

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Mechanism of Action:

Rifampin works by inhibiting bacterial RNA synthesis. It binds to the beta subunit of bacterial RNA polymerase, blocking transcription, which is essential for bacterial replication and survival.

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Spectrum:

1. Mycobacteria:

   • Highly effective against Mycobacterium tuberculosis (TB) and Mycobacterium leprae (leprosy).
   • Active against Mycobacterium avium complex (MAC).

2. Gram-positive bacteria:

   • Effective against Staphylococcus aureus, including MRSA (used only in combination therapy).
   • Covers Streptococcus pneumoniae in combination therapy to prevent resistance.

3. Gram-negative bacteria:

   • Used for prophylaxis of Neisseria meningitidis (meningococcal disease) and Haemophilus influenzae.

4. Anaerobes:

   • Limited activity.

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Key Uses:

1. Tuberculosis (TB):

   • Rifampin is a cornerstone of first-line TB therapy, always used in combination with other drugs (e.g., isoniazid, pyrazinamide) to prevent resistance.

2. MRSA infections (Never used alone):

   • Rifampin should never be used alone to treat MRSA infections, as rapid resistance develops when used as monotherapy. It is typically combined with vancomycin or trimethoprim-sulfamethoxazole for treating MRSA in cases like osteomyelitis or prosthetic infections.

3. Meningococcal prophylaxis:

   • Used for Neisseria meningitidis in close contacts of patients with confirmed meningococcal disease.

4. Leprosy (Hansen’s disease):

   • Combined with dapsone and clofazimine in multidrug therapy for leprosy.

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Key Side Effects:

1. Hepatotoxicity:

   • Rifampin can cause liver damage, particularly when used with other hepatotoxic drugs. Monitoring liver function tests is essential.

2. Red-orange discoloration:

   • A common side effect is the red-orange staining of urine, tears, sweat, and saliva. Patients should be warned that it can stain contact lenses and clothing.

3. Drug interactions:

   • Rifampin is a potent inducer of cytochrome P450 (CYP3A4) enzymes, significantly reducing the effectiveness of many drugs, including oral contraceptives, warfarin, and some antiretrovirals.

4. Thrombocytopenia and flu-like symptoms: Rarely, patients may experience low platelet counts or flu-like symptoms with intermittent use.

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Key Notes:

• Never use alone in MRSA: Rifampin must always be used in combination with other antibiotics when treating MRSA infections, as monotherapy leads to rapid resistance. This is critical when treating serious infections like prosthetic joint infections or osteomyelitis.
• Combination therapy for TB and leprosy: Always part of multidrug regimens for TB and leprosy to prevent resistance.
• Prophylaxis: Effective in short-term use for meningococcal and H. influenzae meningitis prevention in close contacts.

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Summary:

• Rifampin is a key antibiotic for tuberculosis, leprosy, and MRSA infections, but it should never be used alone for MRSA, due to the risk of rapid resistance.
• It has significant drug interactions and can cause liver toxicity, requiring careful monitoring.
• Red-orange discoloration of bodily fluids is common and harmless but can cause staining.

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