Fusidic Acid

• Fusidic acid is a steroidal antibiotic with a molecular formula of C31H48O6 and a molecular mass of 516.72 g/mol. Its structure features a tetracyclic steroid nucleus with a unique fusidane ring system and a carboxylic acid side chain, which are critical for its antibacterial activity. This distinctive structure classifies it as a member of the fusidane family and distinguishes it from other classes of antibiotics.
• The antibiotic exerts its bacteriostatic action by inhibiting bacterial protein synthesis. It specifically binds to elongation factor G (EF-G), a key component of the bacterial ribosome, preventing the release of this factor after translocation during the elongation phase of protein synthesis. This mechanism halts the ribosomal cycle, effectively stopping bacterial growth. At higher concentrations, fusidic acid can also exhibit bactericidal activity against highly susceptible organisms.
• Fusidic acid demonstrates potent activity against a narrow spectrum of gram-positive bacteria, particularly Staphylococcus aureus (including methicillin-resistant strains, MRSA) and Staphylococcus epidermidis. It is also effective against some gram-positive cocci, such as Corynebacterium species and Clostridium species, but has limited activity against gram-negative bacteria due to poor penetration of the outer membrane.
• The pharmacokinetic profile of fusidic acid includes good oral bioavailability (approximately 90%), rapid absorption, and extensive tissue distribution. It achieves high concentrations in bone, skin, and soft tissues, making it particularly useful for treating skin and soft tissue infections, osteomyelitis, and prosthetic joint infections. Fusidic acid is primarily metabolized in the liver and excreted in bile, with minimal renal excretion. Its half-life ranges from 9 to 14 hours, allowing for once- or twice-daily dosing.
• Despite its efficacy, fusidic acid is associated with potential adverse effects, including gastrointestinal disturbances (e.g., nausea, vomiting) and, rarely, hepatotoxicity. Its use is also limited by the potential for rapid development of bacterial resistance, particularly when used as monotherapy. Therefore, it is often combined with other antibiotics to reduce the risk of resistance.

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