Bacteriophage Therapy of Ventilator-associated Pneumonia and Empyema Caused by Pseudomonas aeruginosa

Targeted phage display-based pulmonary vaccination in mice and non-human primates

“…The goal of using this approach was to explore the unique mechanisms underlying the attributes of the CAKSMGDIVC ligand peptide and its functional interaction with the corresponding receptor a3b1 integrin expressed on lung epithelial cells, to develop a targeted immunization system based on aerosol delivery. These studies were supported by the emerging success of phage-based therapies [34][35][36][37] and by the encouraging results obtained with aerosol vaccination against the Ebola virus and tuberculosis in non-human primates. 7,9 Of interest, expanding on a related topic, previously published reports by our group also show that ligand-directed phage particles are able to target lymph nodes preferentially to induce specific systemic humoral responses.…”

Targeting Plasmids to Limit Acquisition and Transmission of Antimicrobial Resistance

“…Schooley et al (2017) have used phagotherapy in a patient with necrotic pancreatitis caused by a MDR strain of A. baumannii. Other studies have obtained favorable results for the phagotherapy of an aortic graft infection with P. aeruginosa (Chan et al, 2018), pneumonia caused by a MDR strain of P. aeruginosa in a cystic fibrosis patient (Law et al, 2019), a Mycobacterium abscessus infection in a patient with cystic fibrosis (Dedrick et al, 2019), and periprosthetic, musculoskeletal, and lung infections (Maddocks et al, 2019;Onsea et al, 2019;Tkhilaishvili et al, 2019). Contrary to these studies, there are reports of the inefficiency of phages in treating bacterial infections (Sarker et al, 2016;Jault et al, 2019), which suggests that the clinical use of phages requires standardization.…”

Turning the Phage on Treatment of Antimicrobial-Resistant Pneumonia

“…In contrast to the disappointing results of the animal study, Maddocks and colleagues (pp. 1179–1181) report a case of multilobar cavitary extremely drug-resistant Pseudomonas VAP, complicated by an infected bronchopleurocutaneous fistula, that responded dramatically to both intravenous and aerosol treatment with a customized four-phage cocktail (9). Not only did the patient respond clinically, but repeat sampling could not detect any further P. aeruginosa .…”

“…The emergence of resistance was found to be a cause of treatment failure in a wound infection study, one of the very few randomized controlled trials of phage treatment to be conducted in humans (12). The bacterial clearance in the Pseudomonas pneumonia case despite the likely high bacterial load is therefore that much more impressive (9).…”

“…The optimal method for delivering phage therapy for pneumonia is also unclear. Addition of aerosolized phages resulted in dramatic bacterial clearance in the Pseudomonas case (9), but intravenous-only administration did not result in eradication of MRSA in the experimental model (8). A higher lung necrosis score was associated with nonsurvival ( see Figure E3 in Reference 8), raising concerns about intravenous delivery of both phage and antibiotic to the lumen of cavitary pneumonia.…”