Phage Therapy Experience at the Eliava Phage Therapy Center: Three Cases of Bacterial Persistence

Abstract

In this retrospective descriptive study we focus on cases of three patients who underwent phage therapy procedures at Eliava Phage Therapy Center (EPTC) in Tbilisi, Georgia. Patients with chronic infectious diseases related to Pseudomonas aeruginosa (two patients, lower respiratory tract infection (LRTI)) and Klebsiella pneumoniae (one patient, urinary tract infection (UTI)) are among those very few EPTC patients whose pathogens persisted through phage therapy. By looking at bacterial strains and personalized phages used against them we tried to point towards possible adaptation strategies that are employed by these pathogens. Genome restriction-based Pulsed Field Gel Electrophoresis (PFGE) profiling of strains isolated before and after phage therapy hints towards two strategies of adaptation. In one patient case (Pseudomonas aeruginosa related lung infection) bacterial strains before and after phage therapy were indistinguishable according to their PFGE profiles, but differed in their phage susceptibility properties. On the other hand, in two other patient cases (Pseudomonas aeruginosa related LRTI and Klebsiella pneumoniae related UTI) bacterial adaptation strategy seemed to have resulted in diversification of infecting strains of the same species. With this work we want to attract more attention to phage resistance in general as well as to its role in phage therapy.

Keywords: Klebsiella pneumoniae; Pseudomonas aeruginosa; phage therapy.

Figure 1

EPTC custom phage orders according to years (a) and bacterial species targeted by requested custom phages (b). Three full years and 6 months of the year 2021 are shown. Values in white (left part of the bar—darker shade of bar color) indicate numbers of primary custom phage orders, while values in black (right part of the bar—lighter shade of bar color) indicate numbers of custom phage re-orders from the same patients (a). Bacterial species distribution is shown cumulatively for 705 custom phage orders received since 2018 (b).

Figure 2

Clustering of Pseudomonas aeruginosa strains of patient #1. Susceptibility to the custom phage is shown across the isolation date of each strain. Cluster 1: P. a. from 3 April 2017b, P. a. from 9 January 2017, P. a. from 24 January 2017. Cluster 2: P. a. from 1 October 2019, P. a. from 23 September 2017, P. a. from 17 September 2018.

Figure 3

Clustering of Klebsiella pneumoniae strains of patient #3. Vaginal isolates are boxed in grey. Susceptibility to custom phages is shown across the isolation date of each strain. Cluster 1: K. p. (vaginal isolate) from 12 July 2019, K. p. from 8 January 2018, K. p. from 9 January 2019. Cluster 2: K. p. from 9 January 2019, K. p. from 26 March 2018, K. p. from 26 June 2018. Cluster 3: K. p. from 23 April 2019 (vaginal isolate), K. p. from 9 January 2019 (vaginal isolate), K. p. from 9 October 2018, K. p. from 23 April 2019.