Nebulized Bacteriophages for Prophylaxis of Experimental Ventilator-Associated Pneumonia Due to Methicillin-Resistant Staphylococcus aureus.

Prazák, Josef; Valente, Luca; Iten, Manuela; Grandgirard, Denis; Leib, Stephen; Jakob, Stephan M.; Hänggi, Matthias; Que, Yok-Ai; Cameron, David R. (2020). Nebulized Bacteriophages for Prophylaxis of Experimental Ventilator-Associated Pneumonia Due to Methicillin-Resistant Staphylococcus aureus. Critical care medicine, 48(7), pp. 1042-1046. Wolters Kluwer Health 10.1097/CCM.0000000000004352

Preview

Text Nebulized_Bacteriophages_for_Prophylaxis_of.95695 (2).pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (793kB) | Preview

OBJECTIVES

There is a need for alternative strategies to combat and prevent antibiotic-resistant bacterial infections. Here, we assessed the potential for bacteriophage prophylaxis in the context of experimental ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus in rats.

DESIGN

Nebulized phages (aerophages) were delivered to the lungs of rats using a modified vibrating mesh aerosol drug delivery system. Animals were intubated and ventilated for 4 hours, at which point they were infected with methicillin-resistant S. aureus strain AW7 via the endotracheal tube, extubated, and then monitored for 96 hours.

SETTING

Ventilator-associated pneumonia.

SUBJECTS

Male Wistar rats.

INTERVENTIONS

A single application of aerophages prior to ventilation at one of two concentrations (~1010 plaque forming units/mL or ~1011 plaque forming units/mL).

MEASUREMENTS AND MAIN RESULTS

1) Animal survival at 96 hours, 2) enumeration of bacteria and phages in the lungs and spleen, and 3) lung tissue histopathology. Animals that received aerophages prior to ventilation and methicillin-resistant S. aureus challenge showed a higher survival rate compared with untreated controls (60% for animals that received 3 × 10 plaque forming units; 70% for animals that received 3 × 10 plaque forming units; 0% for controls; p < 0.01 for each treatment versus untreated). Surviving animals that received aerophage prophylaxis had fewer methicillin-resistant S. aureus in the lungs compared with untreated control animals that succumbed to pneumonia (1.6 × 10 colony forming units/g vs 8.0 × 10; p < 0.01).

CONCLUSIONS

Prophylactically administered nebulized bacteriophages reduced lung bacterial burdens and improved survival of methicillin-resistant S. aureus infected rats, underscoring its potential in the context of ventilator-associated pneumonia.

Interest & Impact

Downloads

248 since deposited on 04 Jun 2020
50 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item