Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa

Abstract

Bacteriophage therapy has been suggested as an alternative or complementary strategy for the treatment of multidrug resistant (MDR) bacterial infections. Here, we report the favourable clinical evolution of a 41-year-old male patient with a Kartagener syndrome complicated by a life-threatening chronic MDR Pseudomonas aeruginosa infection, who is treated successfully with iterative aerosolized phage treatments specifically directed against the patient’s isolate. We follow the longitudinal evolution of both phage and bacterial loads during and after phage administration in respiratory samples. Phage titres in consecutive sputum samples indicate in patient phage replication. Phenotypic analysis and whole genome sequencing of sequential bacterial isolates reveals a clonal, but phenotypically diverse population of hypermutator strains. The MDR phenotype in the collected isolates is multifactorial and mainly due to spontaneous chromosomal mutations. All isolates recovered after phage treatment remain phage susceptible. These results demonstrate that clinically significant improvement is achievable by personalised phage therapy even in the absence of complete eradication of P. aeruginosa lung colonization.

The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo

“…LPS-5 is a lytic phage that infects Pa . It is a member of the Pakpunavirus family and uses pseudomonal lipopolysaccharide (LPS) for viral entry 14 . A representative transmission electron microscopy image of LPS-5 and representative lytic plaque morphology on Pseudomonas aeruginosa PAO1 are shown in Fig.…”

“…Lytic bacteriophages (phages), viruses that kill bacteria, are an exciting treatment option for AMR bacterial infections [7][8][9][10] . Multiple studies have demonstrated the efficacy of phage therapy against MDR Pa [11][12][13][14] , either alone or in conjunction with conventional antibiotics 15 . Phage therapy is saving lives; however, success has been inconsistent [16][17][18] .…”

Navigating Antibacterial Frontiers: A Panoramic Exploration of Antibacterial Landscapes, Resistance Mechanisms, and Emerging Therapeutic Strategies

“…In contrast, in a lysogenic cycle, incorporation of viral DNA into host DNA occurs . Bacteriophages tend to be specific in terms of the receptors they interact with and the species they can affect/target. , Advantages associated with bacteriophage therapy include effectiveness against MDR bacteria, , specificity in terms of species and/or strains, and leaving the patient’s gut microbiome largely unaltered. , Furthermore, bacteriophage therapy has been shown to have an excellent safety profile in human beings. ,− All of these features mean that as the threat of MDR strains becomes more imminent, bacteriophage therapy has seen a promising resurgence in interest. − In a recent study, a group of researchers designed and administered personalized bacteriophage therapy to an individual suffering from lung infection caused by MDR P. aeruginosa and appeared to be successful in stopping antibiotic therapy completely . Other instances of successful personalized bacteriophage therapy against MDR strains have also been reported .…”

“… 308 , 310 − 312 All of these features mean that as the threat of MDR strains becomes more imminent, bacteriophage therapy has seen a promising resurgence in interest. 313 − 316 In a recent study, a group of researchers designed and administered personalized bacteriophage therapy to an individual suffering from lung infection caused by MDR P. aeruginosa and appeared to be successful in stopping antibiotic therapy completely. 316 Other instances of successful personalized bacteriophage therapy against MDR strains have also been reported.…”

Biophysical Breakthroughs Projected for the Phage Therapy of Bacterial Disease

“…Studies in this general direction have been conducted for (1) stabilizing phages for aerosol delivery [60,61], (2) freeze drying, and (3) in-air spray drying [62][63][64][65]. Spray drying is closest to what happens in the environment.…”