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Phage Therapy Application to Counteract Pseudomonas aeruginosa Infection in Cystic Fibrosis Zebrafish Embryos
Published on: May 12, 2020
Chronic suppression of a multidrug-resistant Pseudomonas aeruginosa in prosthetic joint infection using personalized
Rekha Arya1, Dongzhu Ma1, Jewelia J Rempuszewski1
1Department of Orthopaedic Surgery, Bethel Musculoskeletal Research Center, Arthritis and Arthroplasty Design Lab, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract:
Multidrug resistant (MDR) bacterial infections without antibiotic options are a public health emergency. Infections associated with medical implants serve as an example. Conventional antibiotics have limited ability to eradicate these infections as they are associated with antibiotic-tolerant biofilms. Here, we report the use of bacteriophage therapy for the treatment of a MDR, non-operable Pseudomonas aeruginosa periprosthetic joint infection that had failed multiple antibiotic and surgical interventions. Treatment with intermittent bacteriophage therapy alone without antibiotics over a 2 year time period resulted in clinical resolution of the infection, but not microbiological eradication. Bacteriophage therapy established this control, in part, by altering virulence as defined by disease severity and symptoms and disrupting biofilm. Whole genome sequencing demonstrated the continued presence of bacteriophage during treatment. This provides preliminary evidence that bacteriophage therapy can be used to treat MDR infections in salvage cases when surgical and antibiotic options do not exist.
Insights
Bacteriophage therapy offers a novel treatment for multidrug-resistant (MDR) infections, particularly those linked to medical implants. This approach successfully resolved a severe Pseudomonas aeruginosa infection, demonstrating potential when antibiotics fail.
Area of Science:
- Microbiology
- Infectious Diseases
- Biotechnology
Background:
- Multidrug-resistant (MDR) bacterial infections pose a significant public health threat, especially in cases involving medical implants.
- Conventional antibiotics are often ineffective against biofilms, which protect bacteria and contribute to persistent infections.
- Pseudomonas aeruginosa periprosthetic joint infections are challenging to treat, often requiring extensive interventions.
Purpose of the Study:
- To evaluate the efficacy of bacteriophage therapy as a standalone treatment for a MDR Pseudomonas aeruginosa periprosthetic joint infection.
- To investigate the impact of bacteriophage therapy on infection virulence and biofilm structure.
- To assess the long-term clinical and microbiological outcomes of bacteriophage therapy in a salvage case.
Main Methods:
- A patient with a MDR Pseudomonas aeruginosa periprosthetic joint infection, unresponsive to antibiotics and surgery, received intermittent bacteriophage therapy over two years.
- Whole genome sequencing was employed to monitor bacteriophage presence and potential genetic changes during treatment.
- Clinical symptoms, disease severity, and biofilm characteristics were assessed to evaluate treatment response.
Main Results:
- Bacteriophage therapy alone led to clinical resolution of the infection over the two-year treatment period.
- While clinical symptoms improved, microbiological eradication of Pseudomonas aeruginosa was not achieved.
- Bacteriophage therapy demonstrated an ability to alter bacterial virulence and disrupt biofilm formation.
- Whole genome sequencing confirmed the sustained presence of bacteriophages throughout the treatment duration.
Conclusions:
- Bacteriophage therapy presents a viable therapeutic option for managing MDR infections in salvage situations where conventional treatments are unavailable or have failed.
- The therapy effectively controlled infection symptoms and virulence, highlighting its potential beyond direct bacterial killing.
- Further research is warranted to optimize bacteriophage therapy protocols for complete microbiological eradication in chronic infections.
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