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4. Alginate microbeads and hydrogels delivering meropenem and bacteriophages to treat Pseudomonas aeruginosa fracture-related infections

Author

Chen, Baixing, Benavente, Luis Ponce, Chittò, Marco, Wychowaniec, Jacek K., Post, Virginia, D'Este, Matteo, Constant, Caroline, Zeiter, Stephan, Feng, Wenli, Moreno, Mercedes González, Trampuz, Andrej, Wagemans, Jeroen, Onsea, Jolien, Richards, R. Geoff, Lavigne, Rob, Moriarty, T. Fintan, and Metsemakers, Willem-Jan

Published
2023
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8. Fracture-related infection

Author

Moriarty, T. Fintan, Metsemakers, Willem-Jan, Morgenstern, Mario, Hofstee, Marloes I., Vallejo Diaz, Alejandro, Cassat, James E., Wildemann, Britt, Depypere, Melissa, Schwarz, Edward M., and Richards, R. Geoff

Published
2022
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11. Periprosthetic Joint Infection

Author

Keshishian, Aron, Foster, Andrew, Matziolis, Georg, Moriarty, T. Fintan, Eijer, Henk, Li, Bingyun, editor, Moriarty, Thomas Fintan, editor, Webster, Thomas, editor, and Xing, Malcolm, editor

Published
2020
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12. Isolation and Antibiofilm Activity of Bacteriophages against Cutibacterium acnes from Patients with Periprosthetic Joint Infection.

Author

Chen, Baixing, Chittò, Marco, Tao, Siyuan, Wagemans, Jeroen, Lavigne, Rob, Richards, R. Geoff, Metsemakers, Willem-Jan, and Moriarty, T. Fintan

Subjects
PROSTHESIS-related infections, CUTIBACTERIUM acnes, BIOFILMS, BIOMASS, TITANIUM, BACTERIOPHAGES
Abstract

Background: Infections following shoulder surgery, particularly periprosthetic joint infection (PJI), are challenging to treat. Cutibacterium acnes is the causative pathogen in 39% to 76% of these cases. This study explores the efficacy of bacteriophage therapy as an alternative to conventional antibiotics for treating such infections. Methods: Nine phages with lytic activity were isolated from the skin of humans using C. acnes ATCC 6919 as the indicator host. These phages were tested individually or in combination to assess host range and antibiofilm activity against clinical strains of C. acnes associated with PJIs. The phage cocktail was optimized for broad-spectrum activity and tested in vitro against biofilms formed on titanium discs to mimic the prosthetic environment. Results: The isolated phages displayed lytic activity against a range of C. acnes clinical isolates. The phage cocktail significantly reduced the bacterial load of C. acnes strains 183, 184, and GG2A, as compared with untreated controls (p < 0.05). Individual phages, particularly CaJIE7 and CaJIE3, also demonstrated significant reductions in bacterial load with respect to specific strains. Moreover, phages notably disrupted the biofilm structure and reduced biofilm biomass, confirming the potential of phage therapy in targeting biofilm-associated infections. Conclusions: Our preclinical findings support the potential of phage therapy as a viable adjunct to traditional antibiotics for treating C. acnes infections in orthopedic device-related infections. The ability of phages to disrupt biofilms may be particularly beneficial for managing infections associated with prosthetic implants. [ABSTRACT FROM AUTHOR]

Published
2024
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15. 2023 International Consensus Meeting on Musculoskeletal Infection: Summary from the Treatment Workgroup and Consensus on Treatment in Preclinical Models

Author

Amber Jennings, J, Arts, Chris, Falconer, Robert, Ashton, Nicholas, Williams, Dustin, Duffy, Hannah, Hamilton, John, Markovics, Adrienn, Gianotti, Sofia, Tate, Jermiah, Montgomery, Emily C, Abuhussein, Ezzuddin, Dintakurthi, Yogita, Ren, Youliang, Weeks, Jason, Xie, Chao, Ricciardi, Benjamin, van Hoogstraten, Sanne, Mdingi, Vuyisa, Vanvelk, Niels, Hylen, Annika, Baertl, Susanne, Alt, Volker, Morgenstern, Mario, Priddy, Lauren B, Tucker, Luke J, Gautreaux, Malley A, Ducheyne, Paul, Bhattacharyya, Sanjib, Obremskey, William T, Libos, Andres, Cain, Jarrett D, Hickok, Noreen J, Schwarz, Edward M, Fintan Moriarty, T, Amber Jennings, J, Arts, Chris, Falconer, Robert, Ashton, Nicholas, Williams, Dustin, Duffy, Hannah, Hamilton, John, Markovics, Adrienn, Gianotti, Sofia, Tate, Jermiah, Montgomery, Emily C, Abuhussein, Ezzuddin, Dintakurthi, Yogita, Ren, Youliang, Weeks, Jason, Xie, Chao, Ricciardi, Benjamin, van Hoogstraten, Sanne, Mdingi, Vuyisa, Vanvelk, Niels, Hylen, Annika, Baertl, Susanne, Alt, Volker, Morgenstern, Mario, Priddy, Lauren B, Tucker, Luke J, Gautreaux, Malley A, Ducheyne, Paul, Bhattacharyya, Sanjib, Obremskey, William T, Libos, Andres, Cain, Jarrett D, Hickok, Noreen J, Schwarz, Edward M, and Fintan Moriarty, T

Abstract

In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location and implants used, there are also a wide range of animal models described modelling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to 1) animal model considerations, 2) outcome measurements, and 3) imaging. This article is protected by copyright. All rights reserved.

Published
2024

16. The 2023 Orthopedic Research Society's international consensus meeting on musculoskeletal infection: Summary from the in vitro section

Author

Hickok, Noreen J; https://orcid.org/0000-0001-8501-2817, Li, Bingyun; https://orcid.org/0000-0002-5766-5666, Oral, Ebru; https://orcid.org/0000-0001-5761-719X, Zaat, Sebastian A J; https://orcid.org/0000-0001-9589-186X, Armbruster, David A, Atkins, Gerald J; https://orcid.org/0000-0002-3123-9861, Chen, Antonia F; https://orcid.org/0000-0003-2040-8188, Coraça-Huber, Débora C; https://orcid.org/0000-0001-7664-5989, Dai, Tianhong, Greenfield, Edward M, Kasinath, Rajendra, Libera, Matthew, Marques, Cláudia N H, Moriarty, T Fintan; https://orcid.org/0000-0003-2307-0397, Scott Phillips, K, Raghuraman, Kapil, Ren, Dacheng, Rimondini, Lia, Saeed, Kordo; https://orcid.org/0000-0003-0123-0302, Schaer, Thomas P; https://orcid.org/0000-0002-4340-8212, Schwarz, Edward M; https://orcid.org/0000-0002-4854-9698, Spiegel, Christopher, Stoodley, Paul; https://orcid.org/0000-0001-6069-273X, Truong, Vi Khanh, Tsang, Shao-Ting Jerry, Wildemann, Britt; https://orcid.org/0000-0002-8365-1188, Zelmer, Anja R, Zinkernagel, Annelies S; https://orcid.org/0000-0003-4700-1118, Hickok, Noreen J; https://orcid.org/0000-0001-8501-2817, Li, Bingyun; https://orcid.org/0000-0002-5766-5666, Oral, Ebru; https://orcid.org/0000-0001-5761-719X, Zaat, Sebastian A J; https://orcid.org/0000-0001-9589-186X, Armbruster, David A, Atkins, Gerald J; https://orcid.org/0000-0002-3123-9861, Chen, Antonia F; https://orcid.org/0000-0003-2040-8188, Coraça-Huber, Débora C; https://orcid.org/0000-0001-7664-5989, Dai, Tianhong, Greenfield, Edward M, Kasinath, Rajendra, Libera, Matthew, Marques, Cláudia N H, Moriarty, T Fintan; https://orcid.org/0000-0003-2307-0397, Scott Phillips, K, Raghuraman, Kapil, Ren, Dacheng, Rimondini, Lia, Saeed, Kordo; https://orcid.org/0000-0003-0123-0302, Schaer, Thomas P; https://orcid.org/0000-0002-4340-8212, Schwarz, Edward M; https://orcid.org/0000-0002-4854-9698, Spiegel, Christopher, Stoodley, Paul; https://orcid.org/0000-0001-6069-273X, Truong, Vi Khanh, Tsang, Shao-Ting Jerry, Wildemann, Britt; https://orcid.org/0000-0002-8365-1188, Zelmer, Anja R, and Zinkernagel, Annelies S; https://orcid.org/0000-0003-4700-1118

Abstract

Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of the internet vote. Only two questions received a ≥90% consensus vote, emphasizing the disparate approaches and lack of established consensus for in vitro modeling and interpretation of results. Comments on knowledge gaps and the need for further research on these critical MSKI questions are included.

Published
2024

18. Staphylococcus aureus Panton-Valentine Leukocidin worsens acute implant-associated osteomyelitis in humanized BRGSF mice

Author

Hofstee, Marloes I, primary, Siverino, Claudia, additional, Saito, Motoo, additional, Meghwani, Himanshu, additional, Tapia-Dean, James, additional, Arveladze, Samson, additional, Hildebrand, Maria, additional, Rangel-Moreno, Javier, additional, Riool, Martijn, additional, Zeiter, Stephan, additional, Zaat, Sebastian A J, additional, Moriarty, T Fintan, additional, and Muthukrishnan, Gowrishankar, additional

Published
2024
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20. Clinical management and innovation in fracture non-union.

Author

Siverino, C., Metsemakers, W.-J., Sutter, R., Della Bella, E., Morgenstern, M., Barcik, J., Ernst, M., D'Este, M., Joeris, A., Chittò, M., Schwarzenberg, P., Stoddart, M., Vanvelk, N., Richards, G., Wehrle, E., Weisemann, F., Zeiter, S., Zalavras, C., Varga, P., and Moriarty, T. F.

Published
2024
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23. The 2023 Orthopaedic Research Society's International Consensus Meeting on Musculoskeletal Infection: Summary from the In Vitro Section

Author

Hickok, Noreen J., primary, Li, Bingyun, additional, Oral, Ebru, additional, Zaat, Sebastian A. J., additional, Armbruster, David A., additional, Atkins, Gerald J., additional, Chen, Antonia F., additional, Coraça‐Huber, Débora C., additional, Dai, Tianhong, additional, Greenfield, Edward M., additional, Kasinath, Rajendra, additional, Libera, Matthew, additional, Marques, Cláudia N. H., additional, Moriarty, T. Fintan, additional, Scott Phillips, K., additional, Raghuraman, Kapil, additional, Ren, Dacheng, additional, Rimondini, Lia, additional, Saeed, Kordo, additional, Schaer, Thomas P., additional, Schwarz, Edward M., additional, Spiegel, Christopher, additional, Stoodley, Paul, additional, Truong, Vi Khanh, additional, Tsang, Shao‐Ting Jerry, additional, Wildemann, Britt, additional, Zelmer, Anja R., additional, and Zinkernagel, Annelies S., additional

Published
2023
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24. 2023 International Consensus Meeting on Musculoskeletal Infection: Summary from the Treatment Workgroup and Consensus on Treatment in Preclinical Models

Author

Amber Jennings, J., primary, Arts, Chris, additional, Falconer, Robert, additional, Ashton, Nicholas, additional, Williams, Dustin, additional, Duffy, Hannah, additional, Hamilton, John, additional, Markovics, Adrienn, additional, Gianotti, Sofia, additional, Tate, Jermiah, additional, Montgomery, Emily C., additional, Abuhussein, Ezzuddin, additional, Dintakurthi, Yogita, additional, Ren, Youliang, additional, Weeks, Jason, additional, Xie, Chao, additional, Ricciardi, Benjamin, additional, van Hoogstraten, Sanne, additional, Mdingi, Vuyisa, additional, Vanvelk, Niels, additional, Hylen, Annika, additional, Baertl, Susanne, additional, Alt, Volker, additional, Morgenstern, Mario, additional, Priddy, Lauren B., additional, Tucker, Luke J., additional, Gautreaux, Malley A., additional, Ducheyne, Paul, additional, Bhattacharyya, Sanjib, additional, Obremskey, William T, additional, Libos, Andres, additional, Cain, Jarrett D., additional, Hickok, Noreen J., additional, Schwarz, Edward M., additional, and Fintan Moriarty, T., additional

Published
2023
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25. The global burden of fracture-related infection: can we do better?

Author

Metsemakers, Willem-Jan, primary, Moriarty, T Fintan, additional, Morgenstern, Mario, additional, Marais, Leonard, additional, Onsea, Jolien, additional, O'Toole, Robert V, additional, Depypere, Melissa, additional, Obremskey, William T, additional, Verhofstad, Michael H J, additional, McNally, Martin, additional, Morshed, Saam, additional, Wouthuyzen-Bakker, Marjan, additional, and Zalavras, Charalampos, additional

Published
2023
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27. Impact of Perioperative Dexamethasone Administration on Infection and Implant Osseointegration in a Preclinical Model of Orthopedic Device-Related Infection.

Author

Burch, Marc-Antoine, Keshishian, Aron, Wittmann, Charlotte, Nehrbass, Dirk, Thompson, Keith, Arens, Daniel, Richards, R. Geoff, Mdingi, Vuysa, Chitto, Marco, Morgenstern, Mario, Moriarty, T. Fintan, and Eijer, Henk

Subjects
OSSEOINTEGRATION, ANIMAL models in research, PROSTHESIS-related infections, LABORATORY rats, DEXAMETHASONE, ARTIFICIAL joints, SUMATRIPTAN
Abstract

Glucocorticoids may be given prior to major orthopedic surgery to decrease postoperative nausea, vomiting, and pain. Additionally, many orthopedic patients may be on chronic glucocorticoid therapy. The aim of our study was to investigate whether glucocorticoid administration influences Orthopedic-Device-Related Infection (ODRI) in a rat model. Screws colonized with Staphylococcus epidermidis were implanted in the tibia of skeletally mature female Wistar rats. The treated groups received either a single shot of dexamethasone in a short-term risk study, or a daily dose of dexamethasone in a longer-term interference study. In both phases, bone changes in the vicinity of the implant were monitored with microCT. There were no statistically significant differences in bacteriological outcome with or without dexamethasone. In the interference study, new bone formation was statistically higher in the dexamethasone-treated group (p = 0.0005) as revealed by CT and histopathological analysis, although with relatively low direct osseointegration of the implant. In conclusion, dexamethasone does not increase the risk of developing periprosthetic osteolysis or infection in a pre-clinical model of ODRI. Long-term administration of dexamethasone seemed to offer a benefit in terms of new bone formation around the implant, but with low osseointegration. [ABSTRACT FROM AUTHOR]

Published
2024
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35. List of Contributors

Author

Altiok, Eda, primary, Alvis, Mark R., additional, Arramon, Yves P., additional, Baykal, Doruk, additional, Berg-Johansen, Britta, additional, Brady, M., additional, Briscoe, Adam, additional, Brockett, Claire L., additional, Cordaro, N.M., additional, Day, Judd, additional, Eglin, David, additional, Fintan Moriarty, T., additional, Garcia-Leiner, Manuel, additional, Geoff Richards, R., additional, Ghita, Oana, additional, Graham, Jove, additional, Green, Stuart, additional, Hickok, Noreen J., additional, Hovda, David, additional, Ishihara, Kazuhiko, additional, Jaekel, David J., additional, Jarman-Smith, Marcus, additional, Kurtz, Steven M., additional, Kyomoto, Masayuki, additional, Lal, Saurabh, additional, Lanman, Todd, additional, Lovald, Scott, additional, Lui, Melissa K.C., additional, McKay, Robert, additional, Moro, Toru, additional, Nevelos, Jim, additional, Ong, Kevin, additional, Ouellette, E., additional, Pasko, Kinga M., additional, Peck, Jonathan, additional, Plaza-Castro, Marta, additional, Poulsson, Alexandra H.C., additional, Reitman, Maureen, additional, Rimnac, Clare M., additional, Robotti, Pierfrancesco, additional, Rochford, Edward T.J., additional, Roeder, Ryan K., additional, Sereno, Nuno, additional, Siewert, Bernd, additional, Siskey, Ryan, additional, Sobieraj, Michael C., additional, Stratton-Powell, Ashley A., additional, Tipper, Joanne L., additional, Toth, Jeffrey M., additional, Underwood, Richard J., additional, Walsh, W.R., additional, and Zappini, Gianluca, additional

Published
2019
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36. Bacterial Interactions With PEEK

Author

Hickok, Noreen J., primary, Rochford, Edward T.J., additional, Jaekel, David J., additional, Geoff Richards, R., additional, Fintan Moriarty, T., additional, and Poulsson, Alexandra H.C., additional

Published
2019
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37. The 2023 Orthopedic Research Society's international consensus meeting on musculoskeletal infection: Summary from the in vitro section.

Author

Hickok, Noreen J., Li, Bingyun, Oral, Ebru, Zaat, Sebastian A. J., Armbruster, David A., Atkins, Gerald J., Chen, Antonia F., Coraça‐Huber, Débora C., Dai, Tianhong, Greenfield, Edward M., Kasinath, Rajendra, Libera, Matthew, Marques, Cláudia N. H., Moriarty, T. Fintan, Scott Phillips, K., Raghuraman, Kapil, Ren, Dacheng, Rimondini, Lia, Saeed, Kordo, and Schaer, Thomas P.

Subjects
INTERNET voting, INFECTION, BIOFILMS
Abstract

Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of the internet vote. Only two questions received a ≥90% consensus vote, emphasizing the disparate approaches and lack of established consensus for in vitro modeling and interpretation of results. Comments on knowledge gaps and the need for further research on these critical MSKI questions are included. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Key aspects of soft tissue management in fracture-related infection: recommendations from an international expert group.

Author

Marais, Leonard C., Hungerer, Sven, Eckardt, Henrik, Zalavras, Charalampos, Obremskey, William T., Ramsden, Alex, McNally, Martin A., Morgenstern, Mario, Metsemakers, Willem-Jan, Atkins, Bridget L., Borens, Olivier, Depypere, Melissa, Egol, Kenneth A., Fragomen, Austin T., Onsea, Jolien, Govaert, Geertje A. M., Kates, Stephen L., Kuehl, Richard, Mcfadyen, Ian, and Fintan Moriarty, T.

Subjects
NEGATIVE-pressure wound therapy, MICROBIAL cultures, SURGICAL site
Abstract

A judicious, well-planned bone and soft tissue debridement remains one of the cornerstones of state-of-the-art treatment of fracture-related infection (FRI). Meticulous surgical excision of all non-viable tissue can, however, lead to the creation of large soft tissue defects. The management of these defects is complex and numerous factors need to be considered when selecting the most appropriate approach. This narrative review summarizes the current evidence with respect to soft tissue management in patients diagnosed with FRI. Specifically we discuss the optimal timing for tissue closure following debridement in cases of FRI, the need for negative microbiological culture results from the surgical site as a prerequisite for definitive wound closure, the optimal type of flap in case of large soft tissue defects caused by FRI and the role of negative pressure wound therapy (NPWT) in FRI. Finally, recommendations are made with regard to soft tissue management in FRI that should be useful for clinicians in daily clinical practice. Level of evidence Level V. [ABSTRACT FROM AUTHOR]

Published
2024
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39. A doxycycline-loaded polymer-lipid encapsulation matrix coating for the prevention of implant-related osteomyelitis due to doxycycline-resistant methicillin-resistant Staphylococcus aureus

Author

Metsemakers, Willem-Jan, Emanuel, Noam, Cohen, Or, Reichart, Malka, Potapova, Inga, Schmid, Tanja, Segal, David, Riool, Martijn, Kwakman, Paulus H.S., de Boer, Leonie, de Breij, Anna, Nibbering, Peter H., Richards, R. Geoff, Zaat, Sebastian A.J., and Moriarty, T. Fintan

Published
2015
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43. Disease-associated genotypes of the commensal skin bacterium Staphylococcus epidermidis

Author

Méric, Guillaume, Mageiros, Leonardos, Pensar, Johan, Laabei, Maisem, Yahara, Koji, Pascoe, Ben, Kittiwan, Nattinee, Tadee, Phacharaporn, Post, Virginia, Lamble, Sarah, Bowden, Rory, Bray, James E., Morgenstern, Mario, Jolley, Keith A., Maiden, Martin C. J., Feil, Edward J., Didelot, Xavier, Miragaia, Maria, de Lencastre, Herminia, Moriarty, T. Fintan, Rohde, Holger, Massey, Ruth, Mack, Dietrich, Corander, Jukka, and Sheppard, Samuel K.

Published
2018
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46. Multiple hypervirulent methicillin-sensitiveStaphylococcus aureuslineages contribute towards poor patient outcomes in orthopedic device-related infections

Author

Post, Virginia, primary, Pascoe, Ben, additional, Mourkas, Evangelos, additional, Calland, Jessica K., additional, Hitchings, Matthew D., additional, Erichsen, Christoph, additional, Fischer, Julian, additional, Morgenstern, Mario, additional, Richards, R. Geoff, additional, Sheppard, Samuel K., additional, and Moriarty, T. Fintan, additional

Published
2022
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50. Duration of Perioperative Antibiotic Prophylaxis in Open Fractures:A Systematic Review and Critical Appraisal

Author

Vanvelk, Niels, Chen, Baixing, Van Lieshout, Esther M.M., Zalavras, Charalampos, Moriarty, T. Fintan, Obremskey, William T., Verhofstad, Michael H.J., Metsemakers, Willem Jan, Vanvelk, Niels, Chen, Baixing, Van Lieshout, Esther M.M., Zalavras, Charalampos, Moriarty, T. Fintan, Obremskey, William T., Verhofstad, Michael H.J., and Metsemakers, Willem Jan

Abstract

Fracture-related infection (FRI) remains a serious complication in open fracture care. Adequate surgical treatment and perioperative antibiotic prophylaxis (PAP) are key factors influencing the outcome. However, data concerning the optimal duration of PAP is scarce. The aim of this systematic review was to provide an overview of current evidence on the association between PAP duration and FRI in open fractures. A comprehensive search on 13 January 2022, in Embase, Medline, Cochrane, Web of Science and Google Scholar revealed six articles. Most studies compared either 1 day versus 5 days of PAP or included a cut-off at 72 h. Although prolonged PAP was not beneficial in the majority of patients, the variety of antibiotic regimens, short follow-up periods and unclear description of outcome parameters were important limitations that were encountered in most studies. This systematic review demonstrates a lack of well-constructed studies investigating the effect of PAP duration on FRI. Based on the available studies, prolonged PAP does not appear to be beneficial in the prevention of FRI in open fractures. However, these results should be interpreted with caution since all included studies had limitations. Future randomized trials are necessary to answer this research question definitively.

Published
2022

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