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Therapeutic intratracheal application of a lytic phage against Acinetobacter baumannii lung infection in mice

: Wienhold, Sandra-Maria; Brack, Markus; Nouailles, Geraldine; Seitz, Claudius; Ross, Anton; Ziehr, Holger; Gurtner, Corinne; Dietert, Kristina; Gruber, Achim D.; Rohde, Manfred; Suttorp, Norbert W.; Rohde, Christine; Witzenrath, Martin


Pneumologie 72 (2018), No.S01, pp.S67-S68
ISSN: 0934-8387
Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (Kongress) <59, 2018, Dresden>
Fraunhofer ITEM ()

Introduction: Lung and airway infections by multidrug-resistant bacteria including Acinetobacter baumannii are increasingly causes of concern. High specificity of bacteriophages and their effectivity in lysis make phage therapy attractive to overcome this problem. However, phages need to be properly chosen and characterized according to quality standards, and preparations must be highly purified.
Objectives: This preclinical study aimed at determining the efficacy, safety and tolerability of a novel phage preparation in anticipation of a future clinical trial applying aerosolized lytic phages against A. baumannii.
Methods: Phage Acibel004 was produced as high-titer suspension subjected to final processing including highly efficient depletion of endotoxins by chromatography. Mice were transnasally infected with A. baumannii and 12h p.i. treated intratracheally with phage or solvent. At defined time points clinical parameters were measured, bacterial burden determined and cell-influx analyzed. Lung permeability and cytokine release were measured and histological analyses performed. Furthermore, presence of vital phages was determined.
Results: Phage application in uninfected mice did not cause measurable immune responses. In A. baumannii infected mice, phage therapy enhanced recovery from infection-associated hypothermia and improved clinical outcome. Bacterial loads in lungs and BALF of the phage-treated group were significantly reduced by 48h p.i.. Cellular recruitment to the lung and blood was unaffected by phage treatment, while lung permeability and cytokine production were significantly reduced. Phages were detected in BALF, lungs and plasma of treated mice. No adverse effects of phage therapy were observed.
Conclusion: For the first time a highly purified phage preparation against A. baumannii was used successfully. The current preclinical data further support the concept of developing a phage-based therapy against pulmonary A. baumannii infections.