Benefits of aerosolized phages for the treatment of pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA): an experimental study in rats.

Prazak, Josef; Valente, Luca; Iten, Manuela; Federer, Lea; Grandgirard, Denis; Soto, Sara; Resch, Gregory; Leib, Stephen L.; Jakob, Stephan M.; Haenggi, Matthias; Cameron, David R.; Que, Yok-Ai (2021). Benefits of aerosolized phages for the treatment of pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA): an experimental study in rats. (In Press). The journal of infectious diseases Oxford University Press 10.1093/infdis/jiab112

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BACKGROUND

The optimal method for delivering phages in the context of ventilator-associated pneumonia (VAP) is unknown. In the current study, we assessed the utility of aerosolized phages (aerophages) for experimental MRSA pneumonia.

METHODS

Rats were ventilated for 4h before induction of pneumonia. Animals received either: 1) aerophages; 2) intravenous (IV) phages; 3) a combination of IV and aerophages; 4) IV linezolid; and 5) a combination of IV linezolid and aerophages. Phages were administered at 2, 12, 24, 48 and 72h, and linezolid at 2, 12, 24, 36, 48, 60 and 72h. The primary outcome was survival at 96h. Secondary outcomes were bacterial and phage counts in tissues, and histopathological scoring of the lungs.

RESULTS

Aerophages (1) and IV phages (2) each rescued 50% of animals from severe MRSA pneumonia (P<0.01 compared to placebo controls). The combination of aerophages and IV phages rescued 91% of animals, which was higher than either monotherapy (P<0.05) (3). Standard-of-care antibiotic linezolid (4) rescued 38% of animals. Linezolid and aerophages (5), however did not synergise in this setting (55% survival).

CONCLUSIONS

Aerosolized phage therapy showed potential for the treatment of MRSA pneumonia in an experimental animal model and warrant further investigation for application in humans.

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
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Prazak, Josef; Valente, Luca Gabriele; Iten, Manuela; Grandgirard, Denis; Soto Martin, Sara; Leib, Stephen; Jakob, Stephan; Hänggi, Matthias; Cameron, David Robert and Que, Yok-Ai

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
600 Technology > 630 Agriculture

ISSN:

1537-6613

Publisher:

Oxford University Press

Funders:

[4] Swiss National Science Foundation ; [UNSPECIFIED] ESICM ; [UNSPECIFIED] Novartis Foundation

Language:

English

Submitter:

Stephen Leib

Date Deposited:

08 Apr 2021 14:58

Last Modified:

08 Apr 2021 14:58

Publisher DOI:

10.1093/infdis/jiab112

PubMed ID:

33668071

Uncontrolled Keywords:

antibiotic resistance inhalative nosocomial infections phage therapy ventilator associated pneumonia

BORIS DOI:

10.48350/154726

URI:

https://boris.unibe.ch/id/eprint/154726

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