• Nicolas Dufour, Laurent Debarbieux, Mélanie Fromentin, and Jean-Damien Ricard.
• 1Department of Microbiology, Institut Pasteur, Molecular Biology of Gene in Extremophiles, Paris, France. 2Institut National de la Santé et la Recherche Médicale, INSERM, IAME, UMR 1137, Paris, France. 3Univ Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France. 4AP-HP, Hôpital Louis Mourier, Service de Réanimation Médico-chirurgicale, Colombes, France.
• Crit. Care Med. 2015 Jun 1; 43 (6): e190-8.

ObjectiveTo study the effect of bacteriophage treatment on highly virulent extraintestinal Escherichia coli pneumonia in mice and compare it with conventional antimicrobial treatment.DesignAnimal investigation.SettingUniversity research laboratory.SubjectsPathogen-free 8-week-old Balb/cJRj male mice.InterventionsTwo bacteriophages (536_P1 and 536_P7) were isolated from sewage using strain 536, a highly virulent extraintestinal E. coli. Their in vitro and in vivo efficacy against strain 536 and a ventilator-associated pneumonia E. coli were tested. The first group of mice were infected by intranasal instillation of bioluminescent strain 536 and received 536_P1 intranasally, ceftriaxone, or control. The second group of mice was infected with the ventilator-associated pneumonia strain and received 536_P7. Adaptation of 536_P7 to this clinical isolate was also evaluated in vitro and in vivo.Measurements And Main ResultsIn vivo efficacy of bacteriophage and antibiotic treatment were assessed by recording bioluminescence for short-time periods and by recording body weight and survival of mice for longer periods. Both treatments improved survival compared with control (100% vs 0%), and in vivo bioluminescence recordings showed a similar rapid decrease of emitted light, suggesting prompt bacterial clearance. The majority of mice infected by the ventilator-associated pneumonia strain were not rescued by treatment with 536_P7; however, in vitro adaptation of this bacteriophage toward the ventilator-associated pneumonia strain led to isolate a variant which significantly improved in vivo treatment efficacy (animal survival increased from 20% to 75%).ConclusionsBacteriophage treatment was as effective as antibiotherapy to provide 100% survival rate in a lethal model of highly virulent E. coli pneumonia. Adaptation of a bacteriophage is a rapid solution to improve its efficacy toward specific strains. These results suggest that phage therapy could be a promising therapeutic strategy for ventilator-associated pneumonia.

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