Could a Virus Eradicate Peri-Prosthetic Biofilm Infections?

Could bacteriophage therapy—the practice of using viruses to treat bacterial infections—prove as or more effective than the current standard of care for eradicating biofilm infections?

A research team from the University of Maryland looked at that exact question and the results of their study: “Assessment of Staphylococcal Clinical Isolates from Periprosthetic Joint Infections for Potential Bacteriophage Therapy,” has just been published in the April 20, 2022, edition of The Journal of Bone and Joint Surgery.

Co-author James Doub, M.D., assistant professor of medicine and director of ambulatory infectious diseases at the University of Maryland School of Medicine's Institute of Human Virology, explained this interesting approach to OTW. “Bacteriophage therapy is a novel therapeutic that utilizes the power of viruses to lyse bacteria. This therapy holds promise in the treatment of periprosthetic joint infections [PJI] given these therapeutics have innate abilities to eradicate biofilm and self-replicate.”

“However, many aspects of this therapeutic are not well understood, leading to poorly reproducible outcomes. In addition, this causes bacteriophages to be used similar to antibiotics, but these agents are very different than conventional antibiotics in many ways. Consequently, knowledge about how a bacteriophage therapeutic’s activity can differ between bacterial phenotypes (planktonic versus sessile) is paramount to thereby create effective and reproducible therapeutics.”

The researchers collected retrospective data for patients who were diagnosed with chronic hip or knee periprosthetic joint infections following the first stage of a two-stage revision protocol (2017 to 2020). They reviewed and categorized the pathogens in 129 cases; Staphylococcus aureus isolates were tested against 15 staphylococcal bacteriophages to determine bacterial growth inhibition over a 48-hour period.

A total of 71 of the 129 samples were taken during revision hip arthroplasty, and 58 were obtained during revision knee arthroplasty. Of the 129 periprosthetic joint infections, 33 could be attributed to S. aureus, with 17 of the 129 due to methicillin-resistant S. aureus and 16 of the 129 due to methicillin-sensitive S. aureus. Coagulase-negative Staphylococcus species accounted for 18 of the 129 PJIs. Twenty-nine of the 129 cases had no culture growth and were deemed culture-negative PJIs.

“Effective bacteriophage therapeutics are potentially available for S. aureus periprosthetic joint infection isolates but we found that there were differences in bacteriophage activity against small-colony variants compared to planktonic isolates.”

“This finding suggests that bacteriophage attachment receptors differ between the different bacterial phenotypes. Without attachment bacteriophages have no activity. Consequently, when using bacteriophage therapy for PJI, in vitro testing of bacteriophage therapeutics against both planktonic and stationary states of a PJI clinical isolate is vital to ensure activity of that bacteriophage therapeutic.”

More Human Data Needed

Dr. Doub went on to say that “Bacteriophages hold promise to treat periprosthetic joint infections in that they may be able to eradicate the biofilm infections without having to undergo revision surgery which would revolutionize the PJI field.”

“This would reduce morbidity, mortality and the immense financial ramifications associated with conventional PJI treatments. As well, the current paradigm is to test bacteriophage therapeutics to only planktonic bacteria cultured from a patient to thereby extrapolate activity of that bacteriophage to all bacteria causing the infection. However, this manuscript shows the importance of testing against planktonic as well as stationary phenotypes given bacteria change their surface receptors to enhance fitness in the stationary states which can alter bacteriophage activity.”