mupirocin and Hemolysis

In this report, we demonstrate the pH-dependent, in vitro antimicrobial activity of a cationic, amphiphilic random copolymer against clinical isolates of drug-resistant Staphylococcus aureus. The polymer was developed toward a long-term goal of potential utility in the treatment of skin infections. The proposed mechanism of action of the polymer is through selectively binding to bacterial membranes and subsequent disruption of the membrane structure/integrity, ultimately resulting in bacterial cell death. The polymer showed bactericidal activity against clinical isolates of methicillin-resistant or vancomycin-intermediate S. aureus. The polymer was effective in killing S. aureus at neutral pH, but inactive under acidic conditions (pH 5.5). The polymer did not exhibit any significant hemolytic activity against human red blood cells or display cytotoxicity to human dermal fibroblasts over a range of pH values (5.5-7.4). These results indicate that the polymer activity was selective against bacteria over human cells. Using this polymer, we propose a new potential strategy for treatment of skin infections using the pH-sensitive antimicrobial polymer agent that would selectively target infections at pH-neutral wound sites, but not the acidic, healthy skin.

Topics: Anti-Bacterial Agents; Cells, Cultured; Erythrocytes; Fibroblasts; Hemolysis; Humans; Hydrogen-Ion Concentration; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mupirocin; Polymers; Staphylococcus aureus; Vancomycin

After strict hygienical measures have been exhausted the use of plastic materials with antibacterial activity may reduce catheter related-bacterial colonization. An antimicrobial silicone catheter was investigated by HPLC-measurement, SEM, antimicrobial assays and standard biocompatibility tests. The modified catheter was highly biocompatible and the antimicrobial leaching non-toxic. The initially release rate was governed by the drug solubility in the 'sink' and surface loading ('burst effect'). The second continuous period depended on the drug velocity in the silicone matrix and was extended up to 100 days with a proportionality to square root of t for each drug. Diffusion exponents were in range of 2 x 10(-8) to 1 x 10(-9) (cm2 sec(-1)). The lower diffusion exponent of mupirocin was explained by its higher cohesion energy and lower physico-chemical compatibility with the embedding silicone. The antimicrobial drugs were in a molecular-dispersed state with the silicone-matrix, whereas superficially located crystals of the antibiotics covering the catheter surface could be demonstrated by SEM.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacterial Adhesion; Biocompatible Materials; Catheterization; Cerebrospinal Fluid Shunts; Delayed-Action Preparations; Erythrocytes; Fusidic Acid; Hemolysis; Humans; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Mupirocin; Rifampin; Silicones; Staphylococcus aureus; Staphylococcus epidermidis