ABSTRACT
A 30-year-old bombing victim with a fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term (>700 days) antibiotic therapy is treated with a pre-adapted bacteriophage along with meropenem and colistin, followed by ceftazidime/avibactam. This salvage therapy results in objective clinical, microbiological and radiological improvement of the patient's wounds and overall condition. In support, the bacteriophage and antibiotic combination is highly effective against the patient's K. pneumoniae strain in vitro, in 7-day mature biofilms and in suspensions.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Resistance, Multiple, Bacterial , Fractures, Bone/microbiology , Klebsiella Infections/microbiology , Klebsiella Infections/therapy , Klebsiella pneumoniae/physiology , Phage Therapy , Adult , Azabicyclo Compounds/pharmacology , Azabicyclo Compounds/therapeutic use , Bacteriophages/genetics , Bacteriophages/ultrastructure , Biofilms/drug effects , Ceftazidime/pharmacology , Ceftazidime/therapeutic use , CpG Islands/genetics , Drug Combinations , Drug Resistance, Microbial/drug effects , Drug Resistance, Microbial/genetics , Fractures, Bone/complications , Fractures, Bone/diagnostic imaging , Genome, Viral , Humans , Klebsiella Infections/complications , Klebsiella Infections/diagnostic imaging , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/isolation & purification , Microbial Sensitivity Tests , Polymorphism, Single Nucleotide/genetics , Proteomics , Replicon/geneticsABSTRACT
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.
Subject(s)
Bacteria , Bacterial Infections , Bacteriophages , Phage Therapy , Adult , Aged , Female , Humans , Male , Middle Aged , Bacteria/virology , Bacterial Infections/therapy , Electrophoresis, Gel, Pulsed-Field , Klebsiella Infections/therapy , Klebsiella pneumoniae , Pseudomonas aeruginosa/virology , Pseudomonas Infections/therapy , Respiratory Tract Infections/therapy , Retrospective Studies , Urinary Tract Infections/therapy , Georgia (Republic)ABSTRACT
In July 2017, a patient presented colonization with a multidrug-resistant, carbapenemase (KPC-3)-producing Klebsiella pneumoniae isolate. A custom-made, lytic bacteriophage preparation was administered to the patient in December 2017, with subsequent eradication of the microorganism and without adverse effects.
