Use of bacteriophages for recalcitrant Pseudomonas aeruginosa periprosthetic joint infection
Location
Philadelphia, PA
Start Date
30-4-2025 1:00 PM
End Date
30-4-2025 4:00 PM
Description
INTRODUCTION
Periprosthetic Joint Infection (PJI) is the most common cause of revision in total knee arthroplasty. Multidrug-resistant (MDR) Pseudomonas aeruginosa PJI is challenging as conventional antibiotic treatments are often ineffective and biofilm formation is prevalent.
Lytic bacteriophages are a relatively untouched treatment with the potential to be an effective therapy in these difficult to treat infections. This study assesses bacteriophage therapy to establish clinical control of a chronic multidrug-resistant (MDR) P.aeruginosa PJI.
METHODS
Prospective study of a patient who presented with a chronic multidrug resistant pseudomonas infection of an ipsilateral hip and knee PJI was performed. After multiple failed surgical and medical interventions, they were placed on palliative care. With FDA expanded access, two separate bacteriophages, PASA16 and Φ83, were injected into the knee and hip 9 times over 26 months.
These bacteriophages were further studied using a C.elegans model. C.elegans were infected with the patient’s clinical isolates of P.aeruginosa followed by phage treatment. Multiple different strains of P.aeruginosa were given with subsequent phage administration, and survival rates were compared to an untreated control group.
To investigate potential phenotypic changes before and after phage therapy, we further characterized P.aeruginosa clinical isolates and biofilm formation. Inhibition and eradication assays were performed with concurrent incubation with Φ83 and PASA16 bacteriophages. These incubations were compared to untreated control P.aeruginosa and examined for biofilm formation.
RESULTS
In a noted improvement to pre-therapy, Clinical control of PJI was maintained on ~3 month injections of Φ83 and PASA16 into joint spaces. The patient continued to culture MDR P.aeruginosa on aspiration cultures, but displayed no clinical or laboratory infectious symptoms.
In the C.elegans model, significant survival increases were seen with all strains of patient cultured P.aeruginosa inoculated C.elegans treated with Φ83 and PASA16 therapy compared to untreated groups. S1 strain (obtained pre-phage-therapy) had 7 day survival rates of 66% and 86% with PASA16 and Φ83, respectively, compared to 13% untreated C.elegans. S8 (obtained during phage-therapy) treated with combined PASA16 and Φ83 post-infection had 86% survival compared to 6.2% untreated with phage. All C.elegans trials (6 P. aeruginosa strains) exhibited significantly improved survival after phage administration.
Biofilm analysis presented significantly reduced biofilm production with phage therapy compared to untreated. Significant biofilm reduction was exhibited with patient-derived pre-phage-treated P.aeruginosa, mid-treatment samples, and post-treatment samples. Additionally, after allowing biofilm to form uninhibited for 48h, treatment with phage therapy exhibited significant biofilm eradication with every stage of patient-derived P.aeruginosa. This quantitative analysis was verified with qualitative analysis through photographic review, further supporting the decrease in biofilm.
DISCUSSION and CONCLUSION
After treatment with PASA16 and Φ83, the study patient exhibited clinical recovery from a chronic PJI unresponsive to prior interventions. Significant survival increases were shown in the C.elegans Kaplan-Meier survival analysis. Additionally, significant reduction in biofilm production, a natural hurdle to PJI infections, was seen in P.aeruginosa strains treated with PASA16 and Φ83. This study emphasizes the potential of bacteriophage therapy in combating PJI and provides valuable insights into biofilm-related mechanisms.
Embargo Period
5-19-2025
Use of bacteriophages for recalcitrant Pseudomonas aeruginosa periprosthetic joint infection
Philadelphia, PA
INTRODUCTION
Periprosthetic Joint Infection (PJI) is the most common cause of revision in total knee arthroplasty. Multidrug-resistant (MDR) Pseudomonas aeruginosa PJI is challenging as conventional antibiotic treatments are often ineffective and biofilm formation is prevalent.
Lytic bacteriophages are a relatively untouched treatment with the potential to be an effective therapy in these difficult to treat infections. This study assesses bacteriophage therapy to establish clinical control of a chronic multidrug-resistant (MDR) P.aeruginosa PJI.
METHODS
Prospective study of a patient who presented with a chronic multidrug resistant pseudomonas infection of an ipsilateral hip and knee PJI was performed. After multiple failed surgical and medical interventions, they were placed on palliative care. With FDA expanded access, two separate bacteriophages, PASA16 and Φ83, were injected into the knee and hip 9 times over 26 months.
These bacteriophages were further studied using a C.elegans model. C.elegans were infected with the patient’s clinical isolates of P.aeruginosa followed by phage treatment. Multiple different strains of P.aeruginosa were given with subsequent phage administration, and survival rates were compared to an untreated control group.
To investigate potential phenotypic changes before and after phage therapy, we further characterized P.aeruginosa clinical isolates and biofilm formation. Inhibition and eradication assays were performed with concurrent incubation with Φ83 and PASA16 bacteriophages. These incubations were compared to untreated control P.aeruginosa and examined for biofilm formation.
RESULTS
In a noted improvement to pre-therapy, Clinical control of PJI was maintained on ~3 month injections of Φ83 and PASA16 into joint spaces. The patient continued to culture MDR P.aeruginosa on aspiration cultures, but displayed no clinical or laboratory infectious symptoms.
In the C.elegans model, significant survival increases were seen with all strains of patient cultured P.aeruginosa inoculated C.elegans treated with Φ83 and PASA16 therapy compared to untreated groups. S1 strain (obtained pre-phage-therapy) had 7 day survival rates of 66% and 86% with PASA16 and Φ83, respectively, compared to 13% untreated C.elegans. S8 (obtained during phage-therapy) treated with combined PASA16 and Φ83 post-infection had 86% survival compared to 6.2% untreated with phage. All C.elegans trials (6 P. aeruginosa strains) exhibited significantly improved survival after phage administration.
Biofilm analysis presented significantly reduced biofilm production with phage therapy compared to untreated. Significant biofilm reduction was exhibited with patient-derived pre-phage-treated P.aeruginosa, mid-treatment samples, and post-treatment samples. Additionally, after allowing biofilm to form uninhibited for 48h, treatment with phage therapy exhibited significant biofilm eradication with every stage of patient-derived P.aeruginosa. This quantitative analysis was verified with qualitative analysis through photographic review, further supporting the decrease in biofilm.
DISCUSSION and CONCLUSION
After treatment with PASA16 and Φ83, the study patient exhibited clinical recovery from a chronic PJI unresponsive to prior interventions. Significant survival increases were shown in the C.elegans Kaplan-Meier survival analysis. Additionally, significant reduction in biofilm production, a natural hurdle to PJI infections, was seen in P.aeruginosa strains treated with PASA16 and Φ83. This study emphasizes the potential of bacteriophage therapy in combating PJI and provides valuable insights into biofilm-related mechanisms.