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

[img]
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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Prazák, Josef; Valente, Luca Gabriele; Iten, Manuela; Grandgirard, Denis; Leib, Stephen; Hänggi, Matthias; Que, Yok-Ai and Cameron, David Robert

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1530-0293

Publisher:

Wolters Kluwer Health

Language:

English

Submitter:

Stephen Leib

Date Deposited:

04 Jun 2020 14:53

Last Modified:

24 Jun 2020 01:32

Publisher DOI:

10.1097/CCM.0000000000004352

PubMed ID:

32304419

BORIS DOI:

10.7892/boris.144282

URI:

https://boris.unibe.ch/id/eprint/144282

Actions (login required)

Edit item Edit item
Provide Feedback