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


Journal

The Journal of bone and joint surgery. American volume
ISSN: 1535-1386
Titre abrégé: J Bone Joint Surg Am
Pays: United States
ID NLM: 0014030

Informations de publication

Date de publication:
20 04 2022
Historique:
pubmed: 16 2 2022
medline: 23 4 2022
entrez: 15 2 2022
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 35167506
doi: 10.2106/JBJS.21.00958
pii: 00004623-202204200-00004
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

693-699

Informations de copyright

Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.

Déclaration de conflit d'intérêts

Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G934).

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Auteurs

Brian J DePalma (BJ)

Department of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, Maryland.

Sumon Nandi (S)

Department of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, Maryland.

Waqas Chaudhry (W)

Adaptive Phage Therapeutics, Gaithersburg, Maryland.

Martin Lee (M)

Adaptive Phage Therapeutics, Gaithersburg, Maryland.

Aaron J Johnson (AJ)

Department of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, Maryland.

James B Doub (JB)

Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland.

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