Hydrogel antimicrobial capture coatings for endotracheal tubes; a pharmaceutical strategy designed to prevent ventilator-associated pneumonia.

摘要

This paper presents a novel strategy for the prevention of ventilator-associatedpneumonia that involves coating poly(vinyl chloride, PVC) endotracheal tubes (ET) withhydrogels that may be subsequently used to entrap nebulized antimicrobial solutions. Candidatehydrogels were prepared containing a range of ratios of hydroxyethyl methacrylate (HEMA) andmethacrylic acid (MAA) from 100:0 to 70:30 using free radical polymerization and, whenrequired, simultaneous attachment to PVC was performed. The mechanical properties, glasstransition temperatures, swelling kinetics, uptake of gentamicin from an aqueous medium, andgentamicin release were characterized. Increasing the MAA content of the hydrogels significantlydecreased the ultimate tensile strength, % elongation at break, Young’s modulus, and increasedthe glass transition temperature, the swelling ratio, and gentamicin uptake. Microbial(Staphylococcus aureus and Pseudomonas aeruginosa) adherence to control (drug-free) hydrogelswas observed; however, while adherence to gentamicin-containing p(HEMA) occurred, noadherence occurred to gentamicin-containing HEMA:MAA copolymers. Antimicrobialpersistence of gentamicin-containing hydrogels was examined by determining the zone ofinhibition against each microorganism on successive days. Hydrogel composition affected the observed antimicrobial persistence,with the hydrogel composed of 70:30 HEMA:MAA exhibiting >20 days persistence against S. aureus and P. aeruginosa,respectively. To simulate clinical use, the hydrogels (coated onto PVC) were first exposed to a nebulized solution of gentamicin(4 mL, 80 mg for 20 min), and then to nebulized bacteria (4 mL ca. 1 × 109 colony forming units mL−1, 30 min). Viable bacteriawere not observed on the gentamicin-treated p(HEMA: MAA) copolymers, whereas growth was observed on gentamicin-treatedp(HEMA). In light of the excellent antimicrobial activity and physicochemical properties, p(HEMA: MAA) copolymerscomposed of ratios of 80:20 or 70:30 HEMA: MAA were identified as potentially useful coatings of endotracheal tubes to be usedin conjunction with the clinical nebulization of gentamicin and designed for the prevention of ventilator-associated pneumonia