Bacteriophages Improve Outcome in Experimental Staphylococcus Aureus Ventilator Associated Pneumonia.

Prazák, Josef; Iten, Manuela; Cameron, David Robert; Save, Jonathan Florian; Grandgirard, Denis; Resch, Gregory; Göpfert, Christine; Leib, Stephen L.; Takala, Jukka; Jakob, Stephan; Que, Yok-Ai; Hänggi, Matthias (2019). Bacteriophages Improve Outcome in Experimental Staphylococcus Aureus Ventilator Associated Pneumonia. American journal of respiratory and critical care medicine, 200(9), pp. 1126-1133. American Thoracic Society 10.1164/rccm.201812-2372OC

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RATIONALE Infections caused by multidrug resistant bacteria are a major clinical challenge. Phage therapy is a promising alternative antibacterial strategy. OBJECTIVE To evaluate the efficacy of intravenous phage therapy for the treatment of ventilator associated pneumonia due to methicillin-resistant Staphylococcus aureus in rats. METHODS A randomized blinded controlled experimental study compared intravenous teicoplanin (3mg/kg, n=12), a cocktail of four phages (2-3 x 10^9 plaque forming units/ml of 2003, 2002, 3A and K, n=12) and combination of both (n=11), given two, 12 and 24 hours after induction of pneumonia, then once daily for four days. The primary outcome was survival at day four. Secondary outcomes were bacterial and phage densities in lungs and spleen, histopathological scoring of infection within the lungs and inflammatory biomarkers in blood. MEASUREMENTS AND MAIN RESULTS Treatment with either phages or teicoplanin increased survival from 0% to 58% and 50% respectively (p<0.005). Combination of phage with antibiotics did not further improve outcome (45% survival). Animal survival correlated with reduced bacterial burden in the lung (1.2 x 10^6 CFU/g of tissue for survivors versus 1.2 x 10^9 CFU/g for non-surviving animals, p<0.0001), as well as improved histopathological outcomes. Phage multiplication within the lung occurred during treatment. IL-1β increased for all treatment groups over the course of therapy. CONCLUSIONS Phage therapy was as effective as teicoplanin in improving survival and decreasing bacterial load within the lungs of rats infected with methicillin-resistant S. aureus. Combining antibiotics with phage therapy did not further improve outcomes. Key Words: bacteriophage; antibiotic resistance, microbial; pneumonia, ventilator associated.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care

UniBE Contributor:

Prazák, Josef; Iten, Manuela; Cameron, David Robert; Save, Jonathan Florian; Grandgirard, Denis; Göpfert, Christine; Leib, Stephen; Jakob, Stephan; Que, Yok-Ai and Hänggi, Matthias

Subjects:

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

ISSN:

1535-4970

Publisher:

American Thoracic Society

Language:

English

Submitter:

Mirella Aeberhard

Date Deposited:

28 Aug 2019 08:59

Last Modified:

03 Nov 2019 01:31

Publisher DOI:

10.1164/rccm.201812-2372OC

PubMed ID:

31260638

Uncontrolled Keywords:

bacteriophage; antibiotic resistance, microbial; pneumonia, ventilator associated

BORIS DOI:

10.7892/boris.132564

URI:

https://boris.unibe.ch/id/eprint/132564

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