Phage Therapy for Pneumonia and Inflammatory Response
“Supported by years of clinical application in some countries and more recently by literature on experimental models as well as compassionate use in Europe and the USA, bacteriophage (phage) therapy offers a solution for difficult-to-treat bacterial infections. However, studies on the impact of such treatments on the host are still rare.
Methods
Acute pneumonia in mice, induced by intranasal instillation of two pathogenic strains of Escherichia coli (536 and LM33), was treated with two specific bacteriophages (536_P1 and LM33_P1; intranasal) or antibiotics (ceftriaxone, cefoxitin, imipenem-cilastatin; intraperitoneal). Healthy mice also received phages only. The severity of pulmonary edema, acute inflammatory cytokines (blood and lung homogenates), complete blood count, bacterial and bacteriophage counts were obtained at early (≤ 12 h) and late (≥ 20 h) time points. (…..)
Results
The efficacy of bacteriophages in reducing bacterial load was faster than that of antibiotics, but both showed similar endpoints. Bacteriophage treatment was not associated with hyperinflammation; on the contrary, it tended toward lower inflammation and allowed faster correction of blood cell count abnormalities compared to antibiotics. In the absence of bacterial infection, bacteriophage 536_P1 promoted a weak increase in the production of antiviral cytokines (IFN-γ and IL-12) and chemokines in the lung, but not in the blood. However, such variations were no longer observed when bacteriophage 536_P1 was administered to treat infected animals.
Conclusions
“The rapid lysis of bacteria by bacteriophages in vivo does not increase the innate inflammatory response compared to antibiotic treatment.”
Source:
Nicolas Dufour, Raphaëlle Delattre, Anne Chevallereau, Jean-Damien Ricard, and Laurent Debarbieux
Phage Therapy for Pneumonia Is Not Associated with an Overstimulation of the Inflammatory Response Compared to Antibiotic Treatment in Mice
https://aac.asm.org/content/early/2019/06/04/AAC.00379-19
Antimicrobial Agents and Chemotherapy, June 2019, AAC.00379-19. DOI: 10.1128/AAC.00379-19
