Adaptive Phage Therapy in the Treatment of Patients with Recurrent Pneumonia (Pilot Study)

Abstract

Aim. To evaluate the safety and efficacy of the adaptive phage therapy technique in patients with recurrent pneumonia in neurological critical care.Material and methods. The clinical study included 83 chronically critically ill patients with severe brain damage. The bacteriophage cocktail selected against specific hospital strains was administered by inhalation to 43 patients. The control group included 40 patients who received conventional antimicrobial therapy. The changes in clinical, laboratory and instrumental parameters, levels of biomarkers, microbiological and PCR tests of bronchoalveolar lavage fluid were assessed, including those in the «phage therapy with antibiotics» (n=29) and «phage therapy without antibiotics» (n=14) subgroups.Results. The groups were comparable in terms of basic parameters (age, sex, diagnosis, organ dysfunction according to APACHE II, use of vasoactive drugs) and the level of airway colonization with antibioticresistant bacterial strains. Good tolerability and absence of clinically significant side effects were observed during inhaled administration of the bacteriophage cocktail. Computed tomography on day 21 showed a significant reduction in lung damage in patients who received bacteriophages. Patients treated with bacteriophages without antibiotics had significantly lower need for mechanical ventilation. The mortality rate on day 28 did not differ significantly and was 4.7% (2/43) in the bacteriophage-treated group vs 5% (2/40) in the control group.Conclusion. The first experience of using the adaptive phage therapy technique in chronically critically ill patients in neurological intensive care demonstrated the safety of inhalational administration of the bacteriophage cocktail. The efficacy of the technique was confirmed by the treatment results obtained in the phage therapy group, which were not inferior to those in the group with conventional antibiotic therapy, while several clinical and laboratory parameters tended to improve even in patients who received bacteriophages and did not receive antibiotics.

Adaptive Phage Therapy for the Prevention of Recurrent Nosocomial Pneumonia: Novel Protocol Description and Case Series

“…This may be due to a reduction in the intensity of the inflammatory response due to a decrease in bacterial load. In conducted studies, a decrease in CRP levels during bacteriophage administration was also noted [16,22].…”

“…Scientists and clinicians in the Russian Federation are developing a comparable approach to legalize the administration of bacteriophages. The difference is that a "cocktail" of bacteriophages is prepared not for an individual patient but for a specific medical institution/department based on the results of bacterial composition monitoring, which is called "adaptive phage therapy" [16]. In order to expand and legitimize the approach, pharmaceutical substances must be registered and manufactured into final forms by compounding pharmacies.…”

Promising Markers of Inflammatory and Gut Dysbiosis in Patients with Post-COVID-19 Syndrome

“…The impact of diet, nutrients, and probiotics in reducing the severity of COVID-19 infection has been suggested [ 11 , 39 , 40 ]. One of the promising measures aimed at correcting the microbiota is a complex phage therapy, which has proven itself in a pilot study with the decrease of Bacteroides fragilis / Faecalibacterium prausnitzii ratio of anaerobic dysbiosis and no side effects in post-COVID-19 rehabilitation and in chronically critically ill patients [ 15 , 41 ]. A study managing COVID-19 with complex oral probiotics in addition to standard treatment showed remission of gastrointestinal symptoms for nearly all patients compared to less than half of the control [ 42 ].…”

Bacteriophages with depolymerase activity in the control of antibiotic resistant Klebsiella pneumoniae biofilms

“…The selected bacteriophages were tested in vivo as a part of a broader phage cocktails in published studies 18 , 19 . Real-time in vitro analysis of K.pneumoniae (Kl 315) culture lysis with a cocktail of selected phages was carried out in a previous study using imaging with a 3D Cell Explorer microscope 19 .…”