{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T08:58:54Z","timestamp":1783069134718,"version":"3.54.6"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tayside Health Fund","award":["2022-2.1.1-NL-2022-00008"],"award-info":[{"award-number":["2022-2.1.1-NL-2022-00008"]}]},{"name":"Tayside Health Fund","award":["739593"],"award-info":[{"award-number":["739593"]}]},{"name":"Tayside Health Fund","award":["L3-2620"],"award-info":[{"award-number":["L3-2620"]}]},{"name":"Tayside Health Fund","award":["P3-0387"],"award-info":[{"award-number":["P3-0387"]}]},{"name":"Tayside Health Fund","award":["HFM 24-17"],"award-info":[{"award-number":["HFM 24-17"]}]},{"name":"National Laboratory of Biotechnology","award":["2022-2.1.1-NL-2022-00008"],"award-info":[{"award-number":["2022-2.1.1-NL-2022-00008"]}]},{"name":"National Laboratory of Biotechnology","award":["739593"],"award-info":[{"award-number":["739593"]}]},{"name":"National Laboratory of Biotechnology","award":["L3-2620"],"award-info":[{"award-number":["L3-2620"]}]},{"name":"National Laboratory of Biotechnology","award":["P3-0387"],"award-info":[{"award-number":["P3-0387"]}]},{"name":"National Laboratory of Biotechnology","award":["HFM 24-17"],"award-info":[{"award-number":["HFM 24-17"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["2022-2.1.1-NL-2022-00008"],"award-info":[{"award-number":["2022-2.1.1-NL-2022-00008"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["739593"],"award-info":[{"award-number":["739593"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["L3-2620"],"award-info":[{"award-number":["L3-2620"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["P3-0387"],"award-info":[{"award-number":["P3-0387"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["HFM 24-17"],"award-info":[{"award-number":["HFM 24-17"]}]},{"name":"Slovenian Research Agency","award":["2022-2.1.1-NL-2022-00008"],"award-info":[{"award-number":["2022-2.1.1-NL-2022-00008"]}]},{"name":"Slovenian Research Agency","award":["739593"],"award-info":[{"award-number":["739593"]}]},{"name":"Slovenian Research Agency","award":["L3-2620"],"award-info":[{"award-number":["L3-2620"]}]},{"name":"Slovenian Research Agency","award":["P3-0387"],"award-info":[{"award-number":["P3-0387"]}]},{"name":"Slovenian Research Agency","award":["HFM 24-17"],"award-info":[{"award-number":["HFM 24-17"]}]},{"name":"Royal Higher Institute of Defence, Belgium","award":["2022-2.1.1-NL-2022-00008"],"award-info":[{"award-number":["2022-2.1.1-NL-2022-00008"]}]},{"name":"Royal Higher Institute of Defence, Belgium","award":["739593"],"award-info":[{"award-number":["739593"]}]},{"name":"Royal Higher Institute of Defence, Belgium","award":["L3-2620"],"award-info":[{"award-number":["L3-2620"]}]},{"name":"Royal Higher Institute of Defence, Belgium","award":["P3-0387"],"award-info":[{"award-number":["P3-0387"]}]},{"name":"Royal Higher Institute of Defence, Belgium","award":["HFM 24-17"],"award-info":[{"award-number":["HFM 24-17"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Bacteriophages (phages) are viruses that infect and kill bacteria. The antimicrobial resistance crisis has driven renewed interest in phage therapy, including the use of phages to treat chronic orthopaedic infections. Methods: Here, we present the results of the first three orthopaedic patients treated with phage therapy in the United Kingdom. Results: The first patient was treated in May 2023 and received phages active against Staphylococcus aureus. At nine months follow-up, the patient\u2019s wound remained healed, the C-reactive protein normal and the patient was walking independently. The second patient received phages active against Klebsiella pneumoniae and S. aureus; the infection remained unresolved. The third patient received phages active against Staphylococcus\u00a0epidermidis; at six months follow-up, the patient was free of infection. Endotoxin was considered at least partially responsible for mild self-limiting adverse effects in two cases. Conclusions: These promising results hint at the potential for phage therapy to transform the care of chronic orthopaedic infections.<\/jats:p>","DOI":"10.3390\/antibiotics14020114","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T03:40:17Z","timestamp":1737517217000},"page":"114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Phage Therapy for Orthopaedic Infections: The First Three Cases from the United Kingdom"],"prefix":"10.3390","volume":"14","author":[{"given":"Daniela I.","family":"Munteanu","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Ninewells Hospital, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Dunn","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Ninewells Hospital, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8627-2378","authenticated-orcid":false,"given":"G\u00e1bor","family":"Apjok","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, National Laboratory of Biotechnology, HUN-REN Biological Research Centre, Temesv\u00e1ri Krt. 62, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint","family":"Kintses","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, National Laboratory of Biotechnology, HUN-REN Biological Research Centre, Temesv\u00e1ri Krt. 62, 6726 Szeged, Hungary"},{"name":"HCEMM-BRC Translational Microbiology Research Group, Budapesti \u00fat 9, 6728 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Griselain","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Griet","family":"Steurs","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Cochez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Djebara","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases ID4C, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2566-0772","authenticated-orcid":false,"given":"Maya","family":"Merabishvili","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6863-5219","authenticated-orcid":false,"given":"Jean-Paul","family":"Pirnay","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Technology, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vida","family":"\u0160tilec","sequence":"additional","affiliation":[{"name":"COBIK, Mirce 21, 5270 Ajdov\u0161\u010dina, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2798-1772","authenticated-orcid":false,"given":"Matja\u017e","family":"Peterka","sequence":"additional","affiliation":[{"name":"COBIK, Mirce 21, 5270 Ajdov\u0161\u010dina, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4420-5952","authenticated-orcid":false,"given":"Emily A.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Ninewells Hospital, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Downie","sequence":"additional","affiliation":[{"name":"Trauma and Orthopaedic Department, Ninewells Hospital, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4960-1846","authenticated-orcid":false,"given":"Alasdair","family":"MacInnes","sequence":"additional","affiliation":[{"name":"Trauma and Orthopaedic Department, Ninewells Hospital, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Nicol","sequence":"additional","affiliation":[{"name":"Trauma and Orthopaedic Department, Ninewells Hospital, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict","family":"Clift","sequence":"additional","affiliation":[{"name":"Trauma and Orthopaedic Department, Ninewells Hospital, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0981-1913","authenticated-orcid":false,"given":"Joshua D.","family":"Jones","sequence":"additional","affiliation":[{"name":"Infection Medicine, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Chancellor\u2019s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/B978-0-12-394438-2.00001-3","article-title":"Phage Therapy-History from Twort and d\u2019Herelle Through Soviet Experience to Current Approaches","volume":"83","author":"Chanishvili","year":"2012","journal-title":"Adv. Virus Res."},{"key":"ref_2","unstructured":"Harper, D.R., Abedon, S.T., Burrowes, B.H., and McConville, M.L. (2018). Current Updates from the Long-Standing Phage Research Centers in Georgia, Poland, and Russia. Bacteriophages, Springer International Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cell.2022.11.017","article-title":"Phage Therapy: From Biological Mechanisms to Future Directions","volume":"186","author":"Strathdee","year":"2023","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e208","DOI":"10.1016\/S1473-3099(21)00612-5","article-title":"Safety and Efficacy of Phage Therapy in Difficult-to-Treat Infections: A Systematic Review","volume":"22","author":"Uyttebroek","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Stacey, H.J., De Soir, S., and Jones, J.D. (2022). The Safety and Efficacy of Phage Therapy: A Systematic Review of Clinical and Safety Trials. Antibiotics, 11.","DOI":"10.3390\/antibiotics11101340"},{"key":"ref_6","first-page":"66","article-title":"Experimental Phage Therapy of Burn Wound Infection: Difficult First Steps","volume":"4","author":"Rose","year":"2014","journal-title":"Int. J. Burn. Trauma"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"237","DOI":"10.12968\/jowc.2009.18.6.42801","article-title":"Bacteriophage Therapy of Venous Leg Ulcers in Humans: Results of a Phase I Safety Trial","volume":"18","author":"Rhoads","year":"2009","journal-title":"J. Wound Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1749-4486.2009.01973.x","article-title":"A Controlled Clinical Trial of a Therapeutic Bacteriophage Preparation in Chronic Otitis Due to Antibiotic-Resistant Pseudomonas Aeruginosa; a Preliminary Report of Efficacy","volume":"34","author":"Wright","year":"2009","journal-title":"Clin. Otolaryngol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ebiom.2015.12.023","article-title":"Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh","volume":"4","author":"Sarker","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S1473-3099(18)30482-1","article-title":"Efficacy and Tolerability of a Cocktail of Bacteriophages to Treat Burn Wounds Infected by Pseudomonas Aeruginosa (PhagoBurn): A Randomised, Controlled, Double-Blind Phase 1\/2 Trial","volume":"19","author":"Jault","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1001\/jamaoto.2019.1191","article-title":"Safety and Tolerability of Bacteriophage Therapy for Chronic Rhinosinusitis Due to Staphylococcus Aureus","volume":"145","author":"Ooi","year":"2019","journal-title":"JAMA Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S1473-3099(20)30330-3","article-title":"Intravesical Bacteriophages for Treating Urinary Tract Infections in Patients Undergoing Transurethral Resection of the Prostate: A Randomised, Placebo-Controlled, Double-Blind Clinical Trial","volume":"21","author":"Leitner","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e02071-21","DOI":"10.1128\/aac.02071-21","article-title":"Considerations for the Use of Phage Therapy in Clinical Practice","volume":"66","author":"Suh","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","unstructured":"Scottish Health Technologies Group (2023, February 24). H.I.S. SHTG Recommendation. Available online: https:\/\/shtg.scot\/our-advice\/bacteriophage-therapy-for-patients-with-difficult-to-treat-bacterial-infections\/."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/cid\/ciac453","article-title":"Phage Therapy of Mycobacterium Infections: Compassionate-Use of Phages in Twenty Patients with Drug-Resistant Mycobacterial Disease","volume":"76","author":"Dedrick","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.clinthera.2023.06.009","article-title":"Phage Therapy for Diabetic Foot Infection: A Case Series","volume":"45","author":"Young","year":"2023","journal-title":"Clin. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1302\/2058-5241.6.210073","article-title":"A Systematic Review of Phage Therapy Applied to Bone and Joint Infections: An Analysis of Success Rates, Treatment Modalities and Safety","volume":"6","author":"McCallin","year":"2021","journal-title":"EFORT Open Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1007\/s00264-024-06295-1","article-title":"Bacteriophage Therapy as an Innovative Strategy for the Treatment of Periprosthetic Joint Infection: A Systematic Review","volume":"48","author":"Yang","year":"2024","journal-title":"Int. Orthop. (SICOT)"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mib.2019.03.005","article-title":"Stronger Together? Perspectives on Phage-Antibiotic Synergy in Clinical Applications of Phage Therapy","volume":"51","author":"Segall","year":"2019","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chang, C., Yu, X., Guo, W., Guo, C., Guo, X., Li, Q., and Zhu, Y. (2022). Bacteriophage-Mediated Control of Biofilm: A Promising New Dawn for the Future. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.825828"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e144","DOI":"10.1093\/cid\/ciaa705","article-title":"Phage Therapy for Limb-Threatening Prosthetic Knee Klebsiella Pneumoniae Infection: Case Report and In Vitro Characterization of Anti-Biofilm Activity","volume":"73","author":"Cano","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","first-page":"24","article-title":"Turning a New Phage on Bone and Joint Infections","volume":"11","author":"Jones","year":"2023","journal-title":"J. Trauma Orthop."},{"key":"ref_23","unstructured":"(2022, September 26). Phage Directory Phage Directory. Available online: https:\/\/phage.directory\/."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"\u0160trancar, V., Maru\u0161i\u0107, M., Tu\u0161ar, J., Pra\u010dek, N., Kolenc, M., \u0160uster, K., Horvat, S., Jane\u017e, N., and Peterka, M. (2023). Isolation and in Vitro Characterization of Novel S. Epidermidis Phages for Therapeutic Applications. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1169135"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Onsea, J., Soentjens, P., Djebara, S., Merabishvili, M., Depypere, M., Spriet, I., De Munter, P., Debaveye, Y., Nijs, S., and Vanderschot, P. (2019). Bacteriophage Application for Difficult-to-Treat Musculoskeletal Infections: Development of a Standardized Multidisciplinary Treatment Protocol. Viruses, 11.","DOI":"10.3390\/v11100891"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s15010-021-01675-w","article-title":"Observed Transaminitis with a Unique Bacteriophage Therapy Protocol to Treat Recalcitrant Staphylococcal Biofilm Infections","volume":"50","author":"Doub","year":"2022","journal-title":"Infection"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1463","DOI":"10.1093\/cid\/ciac694","article-title":"Experience Using Adjuvant Bacteriophage Therapy for the Treatment of 10 Recalcitrant Periprosthetic Joint Infections: A Case Series","volume":"76","author":"Doub","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S407","DOI":"10.1093\/cid\/ciad533","article-title":"Phage Therapy as a Novel Therapeutic for the Treatment of Bone and Joint Infections","volume":"77","author":"Suh","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1302\/2046-3758.812.BJR-2019-0340","article-title":"Prosthetic Joint Infection","volume":"8","author":"Ahmed","year":"2019","journal-title":"Bone Jt. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Garfield, K., Noble, S., Lenguerrand, E., Whitehouse, M.R., Sayers, A., Reed, M.R., and Blom, A.W. (2020). What Are the Inpatient and Day Case Costs Following Primary Total Hip Replacement of Patients Treated for Prosthetic Joint Infection: A Matched Cohort Study Using Linked Data from the National Joint Registry and Hospital Episode Statistics. BMC Med., 18.","DOI":"10.1186\/s12916-020-01803-7"},{"key":"ref_31","unstructured":"(2024, December 10). Clinicaltrials.gov. Clinical Trials of Phage Therapy for Bone and Joint Infections, Available online: https:\/\/www.clinicaltrials.gov\/search?cond=joint%20infection&term=phage%20therapy&rank=1."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/2\/114\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:33:20Z","timestamp":1759919600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/2\/114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,22]]},"references-count":31,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["antibiotics14020114"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14020114","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,22]]}}}