Co-immobilization of ciprofloxacin and chlorhexidine as a long-term, broad-spectrum antimicrobial dual-drug coating for polyvinyl chloride (PVC)-based endotracheal tubes

Abstract

The endotracheal tube (ETT) affords support for intubated patients, but the rising incidence of ventilator-associated pneumonia (VAP) is jeopardizing its application. ETT surfaces promote (poly)microbial colonization and biofilm formation, with a heavy burden for VAP. Devising safe, broad-spectrum antimicrobial materials to tackle ETT bioburden is needful. Herein, we immobilized ciprofloxacin (CIP) and/or chlorhexidine (CHX), through polydopamine (pDA)-based functionalization, onto polyvinyl chloride (PVC) surfaces. These surfaces were characterized and challenged with single and polymicrobial cultures of VAP-relevant bacteria (Pseudomonas aeruginosa; Acinetobacter baumannii; Klebsiella pneumoniae; Staphylococcus aureus; Staphylococcus epidermidis) and fungi (Candida albicans). The coatings imparted PVC surfaces with homogeneous morphology, varied wettability, and low roughness. Coated surfaces exhibited sustained CIP/CHX release, retaining long-term (10 days) stability. Surfaces evidencing no A549 lung cell toxicity exhibited broad-spectrum anti-biofilm activity. CIP/CHX co-immobilization resulted in better outcomes than CIP or CHX coatings, reducing bacteria up to >7 Log10, and modestly distressing (ca. 1 Log10) C. albicans. The anti-biofilm effectiveness of coated surfaces endured for dual biofilms, substantially preventing bacterial populations and fungi (ca. 2.7 Log10) in P. aeruginosa/C. albicans consortia. A less pronounced antifungal effect (ca. 1 Log10 reduction) was found in triple-species communities, but fully preventing P. aeruginosa and S. aureus populations. CIP/CHX co-immobilization holds a safe and robust broad-spectrum antimicrobial coating for PVC-ETTs, with the promise laying in reducing VAP incidence.