Assessment of Staphylococcal Clinical Isolates from Periprosthetic Joint Infections for Potential Bacteriophage Therapy

Abstract

Background: Bacteriophage therapy is a potential adjunctive treatment for periprosthetic joint infections (PJIs) given the capabilities of bacteriophages to degrade biofilms, self-replicate, and lyse bacteria. However, many aspects of this therapeutic are ill-defined, and the narrow spectrum of bacteriophage activity along with limited available bacteriophage strains curb potential use for specific bacteria such as Staphylococcus aureus at the present time. Therefore, the aim of this study was to determine the feasibility of using bacteriophages for PJI by (1) categorizing the causative organisms in hip and knee PJI at a tertiary academic center and (2) evaluating in vitro activity of a group of bacteriophages against clinical S. aureus PJI isolates.Methods: Patients with chronic hip or knee PJI after undergoing the first stage of a 2-stage revision protocol from 2017 to 2020 were identified retrospectively by a query of the hospital billing database. The causative pathogens in 129 cases were reviewed and categorized. From this cohort, preserved S. aureus isolates were tested against a library of 15 staphylococcal bacteriophages to evaluate for bacterial growth inhibition over 48 hours.Results: S. aureus was the most common pathogen causing PJI (26% [33] of 129 cases). Of 29 S. aureus samples that were analyzed for bacteriophage activity, 97% showed adequate growth inhibition of the predominant planktonic colonies by at least 1 bacteriophage strain. However, 24% of the 29 samples demonstrated additional smaller, slower-growing S. aureus colonies, none of which had adequate growth inhibition by any of the initial 14 bacteriophages. Of 5 secondary colonies that underwent subsequent testing with another bacteriophage with enhanced biofilm activity, 4 showed adequate growth inhibition.Conclusions: Effective bacteriophage therapeutics are potentially available for S. aureus PJI isolates. The differences in bacteriophage activity against the presumed small-colony variants compared with the planktonic isolates have important clinical implications. This finding suggests that bacteriophage attachment receptors differ between the different bacterial morphologic states, and supports future in vitro testing of bacteriophage therapeutics against both planktonic and stationary states of PJI clinical isolates to ensure activity.Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G934).

Bacteriophage therapy for periprosthetic joint infections: Current limitations and research needed to advance this therapeutic

“…16 In addition, some bacteriophages have robust abilities to eradicate biofilms and lyse metabolically reduced bacteria while other bacteriophages do not. 19,20 This discordant activity is secondary to the ability of bacteriophages to attach to bacteria in different phenotypes. 19,21 It is therefore a misconception that any bacteriophage can be used as an effective PJI therapeutic.…”

“…19,20 This discordant activity is secondary to the ability of bacteriophages to attach to bacteria in different phenotypes. 19,21 It is therefore a misconception that any bacteriophage can be used as an effective PJI therapeutic.…”

“…PJI caused by S. aureus has the most readily available bacteriophage therapeutics. 19 Other PJI pathogens such as Cutibacterium acne, Coagulase-negative Staphylococcus (CoNS) and Streptococcus spp. have less readily available bacteriophages.…”

Impact of Bacterial Phenotypic Variation with Bacteriophage therapy: A Pilot Study with Prosthetic Joint Infection Isolates

“…De-identified isolates were sent to Adaptive Phage Therapeutics ((APT), Gaithersburg, MD, USA), where 56 unique Staphylococcal bacteriophages, with known lytic activity to S. aureus , were used to assess for bacteriophage-induced growth inhibition. This was conducted by growing each S. aureus isolate in tryptic soy broth to mid-log phase and then diluting to 1 × 10 7 colony-forming units per mL in a 96-microwell plate containing tryptic soy broth with a metabolic indicator dye ( DePalma et al, 2022 ). Individual bacteriophages with titers of 1 to 3 × 10 8 plaque-forming units per mL were then independently introduced into wells with the S. aureus isolates.…”

“…Individual bacteriophages with titers of 1 to 3 × 10 8 plaque-forming units per mL were then independently introduced into wells with the S. aureus isolates. Next, the plates were observed for 48 hours for bacterial growth inhibition, as evidenced by the colorimetric change in the metabolic dye ( DePalma et al, 2022 ). These experiments were repeated in triplicates.…”