Therapeutic intratracheal phage application against Acinetobacter baumannii lung infection in mice

Background: Global spread of multidrug resistant (MDR) bacteria is one of the biggest threats in modern medicine. Acinetobacter baumannii is a feared cause of lung infections particularly in critically ill patients lacking antibiotic options. Therefore, rediscovery of phage therapy has gained attention as treatment option due to its specificity and effectivity. Aims: This preclinical study evaluated the efficacy and safety of a novel phage preparation in a mouse model of A. baumannii lung infection. Methods: Mice were infected with a MDR A. baumannii strain [1]. Phage Acibel004 [2] was produced as suspension including efficient depletion of endotoxins using a newly established protocol. Solvent or phages were sprayed intratracheally 12 hours after infection. Clinical parameters, bacterial load, cell influx, lung permeability and cytokine release were quantified and histopathological examination was performed. Results: Phage-treated mice recovered faster from infection-associated hypothermia. Phage treatment reduced bacterial loads in lungs and BAL 48 hours after infection. Moreover, lung permeability and cytokine release were reduced. Histopathological examination of lungs revealed lesser extent of inflammation in phage-treated mice with unaffected cellular recruitment. No adverse effects were observed. Conclusion: For the first time, a highly purified phage against A. baumannii was successfully used to treat lung infection in vivo. The current preclinical data support the concept of phage-based therapy against pulmonary A. baumannii infections. [1] Knapp, S. et al. Am J Respir Crit Care Med 2006; 1;173(1):122-9 [2] Merabishvili, M. et al. PLoS One 2014; 11;9(8):e104853