Co-immobilization of Ciprofloxacin and Chlorhexidine as a Broad-Spectrum Antimicrobial Dual-Drug Coating for Poly(vinyl chloride) (PVC)-Based Endotracheal Tubes

Abstract

The endotracheal tube (ETT) affords support for intubated patients, but the increasing incidence of ventilatorassociated 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 the ETT bioburden is needful. Herein, we immobilized ciprofloxacin (CIP) and/or chlorhexidine (CHX), through polydopamine (pDA)-based functionalization, onto poly(vinyl chloride) (PVC) surfaces. These surfaces were characterized regarding physicochemical properties 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 a homogeneous morphology, varied wettability, and low roughness. The antimicrobial immobilization via pDA chemistry was still evidenced by infrared spectroscopy. Coated surfaces exhibited sustained CIP/CHX release, retaining prolonged (10 days) activity. CIP/CHX-coated surfaces evidencing no A549 lung cell toxicity displayed better antibiofilm outcomes than CIP or CHX coatings, preventing bacterial attachment by 4.1−7.2 Log 10 CFU/mL and modestly distressingC. albicans. Their antibiofilm effectiveness was endured toward polymicrobial consortia, substantially inhibiting the adhesion of the bacterial populations (up to 8 Log 10 CFU/mL) within the consortia in dual-and even inP. aeruginosa/S. aureus/C. albicans triple-species biofilms while affecting fungal adhesion by 2.7 Log 10 CFU/mL (dual consortia) and 1 Log 10 CFU/mL (triple consortia). The potential of the dual-drug coating strategy in preventing triple-species adhesion and impairing bacterial viability was still strengthened by live/dead microscopy. The pDA-assisted CIP/CHX co-immobilization holds a safe and robust broad-spectrum antimicrobial coating strategy for PVC-ETTs, with the promise laying in reducing VAP incidence.