Inhaled antibiotic therapy for ventilator-associated tracheobronchitis and ventilator-associated pneumonia: an Update

Abstract

Ventilator-associated pneumonia (VAP) remains a leading cause of morbidity and mortality in mechanically-ventilated patients in the Intensive Care Unit (ICU). Ventilator-associated tracheobronchitis (VAT) was previously believed to be an intermediate stage between colonization of the lower respiratory tract and VAP. More recent data, however, suggest that VAT may be a separate entity that increases morbidity and mortality, independently of the occurrence of VAP. Some, but not all, patients with VAT progress to develop VAP. Although inhaled antibiotics alone could be effective for the treatment of VAP, the current consensus of opinion favors their role as adjuncts to systemic antimicrobial therapy for VAP. Inhaled antibiotics are increasingly employed for salvage therapy in patients with VAP due to multi-drug resistant Gram-negative bacteria. In contrast to VAP, VAT could be effectively treated with inhaled antibiotic therapy alone or in combination with systemic antimicrobials.

A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow® Inline Nebulizer System in Mechanically Ventilated Patients

“…(1,2) Adjunctive aerosol antibiotic therapy to treat Gram-negative pneumonia in patients on mechanical ventilation has been studied for over 30 years with encouraging results; however, multicenter, placebocontrolled, randomized trials are needed to establish which antibiotics and drug delivery systems are most efficacious. (3)(4)(5)(6)(7)(8) The emergence of highly resistant Gram-negative bacteria has increased the amount of aminoglycoside required for a 1 Cardeas Pharma, Seattle, WA. 2 Alfred Hospital, Melbourne, Australia.…”

“…Hygroscopic growth from the humidified air in the ventilator circuit can increase the mean droplet size, leading to rainout in the endotracheal tube and poor delivery to the lower airways. (3,13) The airflow from a continuously run jet nebulizer can create a high bias flow that flushes most of the aerosol into the expiratory limb of the ventilator during exhalation by the patient. (3,13) A novel approach to the drug delivery issues was to develop a vibrating plate nebulizer positioned distal to the wye-piece in the ventilator circuit and use breath actuation to deliver the dose only during inhalation.…”

Ventilator-associated infection

“…Studies of adjunctive therapy from 2007 through 2011 have been reviewed previously and will not be covered in detail here [31,57]. Recent colistin studies are included in Table 2.…”

Implications and emerging control strategies for ventilator-associated infections

“…Inhalation therapy is associated with high local antibiotic concentrations within the lung, superior penetrability and much lower systemic toxicity [68]. In a study by Palmer et al, the concentration of aerosolized antibiotic in sputum was 200-fold higher than that achieved through systemic administration [69].…”