Ventilator-associated pneumonia treatment: mortality cofactor in positive COVID-19 patients

Proyecto del Programa de Articulación y Fortalecimiento Federal de las Capacidades en Ciencia y Tecnología Covid-19

Abstract

Sars-CoV-2 infection produces a variety of clinical pictures, including asymptomatic infection, mild upper respiratory disease, and severe viral pneumonia with respiratory failure and even death. The need for hospitalization of the most compromised patients introduces an additional complication, which is the risk of acquiring a hospital infection. Among these, ventilator-associated pneumonia (VAP) is one of the most frequent in Intensive Care Units (ICU) and is currently a complication in the clinical picture of positive COVID-19 patients who need mechanical respiration assistance. The prevention of VAP is crucial to eliminate this cofactor of morbidity and mortality, as well as to reduce the costs associated with health care (long-term care hospitalization, antibiotics, disposable items, etc.).

VAP occurs in patients who are ventilated by an endotracheal tube or tracheotomy, as a host response to bacterial invasion. Patients on mechanical ventilation are unconscious and there is no elimination of secretions in the oropharynx, resulting in an increase in normal oral flora. The colonizing microorganisms pass along the tracheal tube forming biofilms in the internal and external part of the tube, particularly in the region near the bulb. Finally, these microorganisms can reach the distal airways overcoming the immune response of the host and generating pneumonia. The proposal of this work consists of modifying the surface of endotracheal tubes with antimicrobial agents that inhibit bacterial adhesion and proliferation acting as adjuvants of systemically administered antibiotics.

The general objective of this work is to contribute to the prevention of VAP through the functionalization of the internal and external surfaces of the endotracheal tube used in mechanical ventilation. The modification is carried out by depositing a thin film of biocompatible and biodegradable hydrogels loaded with antibiotics and non-conventional antimicrobial agents (silver nanoparticles, AgNPs) to inhibit the formation of bacterial biofilms generating NAV. Hydrogels provide spatial and temporal control over the release of therapeutic agents due to their controllable degradability and ability to protect labile drugs. In addition, higher antibiotic local concentration than those obtained by systemic administration can be reached. To achieve these objectives, the synthesis of a hydrogel based on polyethylene glycol which is capable of strongly adhere to the polyvinyl chloride surface of the endotracheal tube has been optimized. It was possible to cover the surface of the tube with the hydrogel, which showed good mechanical stability for both the dehydrated hydrogel and the hydrated one. Different routes of incorporation of antimicrobial agents were investigated, finding that the most suitable is the addition of these agents to the precursor polymer of the hydrogel. Hydrogels loaded with AgNPs have similar adhesion and stability to the unloaded hydrogels. Experiments are being carried out to determine the antimicrobial capacity of these modified surfaces.