Antibiotics (Properties, Administration, Interactions) - Posokhova K.A., Viktorov O.P. 2005

Other antibiotics
Steroid antibiotics

Fusidin (sodium fusidate). The antibacterial effect of fusidin is associated with the inhibition of bacterial Protein Synthesis through its interaction with elongation factor G, a vital microorganism protein involved in the translocation process on the ribosome during peptide bond formation.

Spectrum of activity. Fusidic acid exhibits bacteriostatic and, at very high doses, bactericidal activity primarily against Gram-positive Bacteria. Fusidic acid shows the greatest efficacy against S. aureus and S. epidermidis, including methicillin-resistant strains. It is also highly active against corynebacteria, meningococci, and neisseriae. Its effect on other staphylococcal species and streptococci is moderate. Gram-negative aerobic bacilli are mostly resistant to fusidic acid. It is characterized by high activity against Gram-positive anaerobes, including clostridia (specifically C. difficile), peptococci, and peptostreptococci. It has a lesser effect on bacteroids and fusobacteria. It demonstrates weak activity against A number of Protozoa (G. lamblia and P. falciparum), as well as Adenoviruses and rhinoviruses.

Pharmacokinetics. Fusidin is well absorbed from the gastrointestinal tract (bioavailability is 90%) and penetrates all Tissues and fluids, except for the CEREBROSPINAL FLUID. It accumulates most intensively in bones, Cartilage tissue, Skin, subcutaneous tissue, and the myocardium, where its concentration reaches 50% of the Blood level. High concentrations of the drug (1.7–6.4 times exceeding the serum concentration) are established in burn surfaces, which is explained by the high protein content. Permeability through intact skin is 0.2–2%. In mechanical trauma and skin diseases, this indicator increases significantly. It penetrates well into purulent discharges. In sputum, the concentration of fusidic acid is 6–8% of the serum level. It crosses the Placenta and is excreted in breast milk. The maximum blood concentration after oral administration is observed in 2–3 hours. It binds to blood Proteins by 90%. The average therapeutic concentration in tissues is maintained for 24 hours. T_1/2 is 5 hours. With prolonged administration, fusidin can accumulate. This effect manifests quickly when administered at 8-hour intervals and is practically absent if the interval between administrations is 12 hours. It is excreted from the body via Bile, where it is found in high concentrations. It is biotransformed in the Liver into inactive metabolites. 0.1% of the drug is excreted in the urine, and 10–15% via the intestines. Renal impairment does not affect its elimination.

Fusidin is used exclusively for the Treatment of patients with severe Staphylococcal infections, particularly those caused by penicillin-resistant microorganisms and when vancomycin cannot be prescribed. Fusidin is indicated for infections of the skin and soft tissues, Bones and joints, eyes, as well as for endocarditis, staphylococcal Sepsis, and other conditions. It is prescribed for pustular skin lesions, acne, abscesses, wound and burn infections, and secondary-infected atopic dermatitis, since S. aureus is the most frequent pathogen in these cases. As an antistaphylococcal agent, fusidin is highly effective in acute and chronic Osteomyelitis, septic Arthritis, and secondary infection of prostheses and osteosynthesis devices.

Fusidin is administered orally at 500 mg every 8 hours or 1 g every 12 hours. An intravenous formulation of the drug is available, allowing for step-down therapy. Intravenous administration of fusidin is carried out in a buffer solution (pH 7.5) very slowly (over 2–4 hours) into a large vein. This administration method is necessary to prevent venous vasospasm, thrombophlebitis, and hemolysis. Intramuscular and subcutaneous injections are contraindicated (risk of necrosis). It can be prescribed topically as an ointment. Upon instillation of a 1% fusidic acid solution (eye drops) into the conjunctival cavity, it penetrates through the cornea into the anterior chamber of the eye, establishing a therapeutic concentration there.

Side effects. During fusidin administration, rapid development of microbial resistance is possible during the course of treatment, so it is advisable to combine it with other antistaphylococcal agents. Gastrointestinal disturbances (vomiting, diarrhea) and hepatic disorders (elevated transaminase levels, development of jaundice) may occur. In newborns, There is a risk of kernicterus (fusidin competes with bilirubin for the glucuronidation system). Therefore, fusidic acid preparations are not prescribed in the third trimester of Pregnancy, during Lactation, in premature infants, or in infants During the first month of life. They are also not recommended for patients with severe liver disease. Intravenous administration of the drugs is contraindicated in obliterating Vascular Diseases.

Interactions. Fusidic acid preparations exhibit synergy when combined with Aminoglycosides and erythromycin. Glycopeptides and fluoroquinolones act as its antagonists. Undesirable drug interaction results of fusidic acid preparations with other agents are presented in Table 43.

Class="center">Table 43. Results of interactions of fusidic acid preparations with other medicinal products (V.P. Yakovlev, S.V. Yakovlev et al.; 2003)