Functionalized polyurethanes releasing rifampin/cefamandole and polyethylen glycol able to prevent bacterial colonization and the emergence of resistant strains.

In last decades, several strategies to prevent bacterial colonization of intravascular catheters and related infections have been developed mostly based on the adsorption and/or entrapment of antimicrobial agents in the polymeric matrix of these medical devices. However, the so far available catheters, impregnated with a couple of differently acting antibiotics, showed a relatively short-term antimicrobial activity, usually no more than 7 days, with a massive antibiotic release within the first 24-48 hrs, followed by the discharge of sub-inhibitory doses until complete release of the adsorbed drugs. Further, these medicated catheters are believed to be possibly associated with a risk of emergence of multidrug-resistant pathogens. To overcome these limits, we developed suitably functionalized polyurethanes able to bind rifampin and cefamandole nafate and to entrap polyethylen glycol (PEG) as a pore former agent. Such experimental model is characterized by both a high polymer/antibiotic affinity and the pore-former dependent property to allow the release of high antibiotic amounts for 3-4 weeks. In fact, due to the presence of PEG, entrapped in the polymeric bulk with the antibiotics, the system was able to inhibit the growth of a rifampin resistant strain of Staphylococcus aureus for 23 days. Further, a synergistic effect of the two antibiotic molecules released from the polymers was also observed. These results suggest that a combined entrapment of suitable antibiotic and pore former molecules into functionalized polyurethanes could represent a new promising approach to prevent microbial colonization and to limit the emergence of antibiotic resistant microrganisms.