{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:12:13Z","timestamp":1784121133554,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heraeus (Germany)","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Gram-negative bacilli can be responsible for prosthetic joint infection (PJI) even if staphylococci are the main involved pathogens. Gram-negative PJIs (GN-PJI) are considered difficult-to-treat infections due to the increase in antimicrobial resistance and biofilm formation. To minimize the risk of infection in cases of arthroplasties with cemented prosthesis, bone cement can be loaded with antibiotics, especially gentamicin. In this study, we aimed to compare the prophylactic antibiofilm activity of ready-to-use antibiotic-loaded bone cements (ALBC), already commercialized or new prototypes. We compared ALBCs containing gentamicin alone, gentamicin plus vancomycin, gentamicin plus clindamycin, gentamicin plus Fosfomycin, and fosfomycin alone, to plain cement (no antibiotic); these comparisons were conducted to investigate the biofilm formation of three strains of Escherichia coli, three strains of Pseudomonas aeruginosa and two strains of Klebsiella pneumoniae, with or without specific resistance to gentamicin or fosfomycin. We reported that ALBC containing gentamicin and clindamycin (COPAL G+C) seems to be the most interesting ALBC of our tested panel for the prevention of biofilm formation by gentamicin-susceptible strains, even if clindamycin is not effective against Gram-negative bacteria. However, gentamicin-resistant strains are still a problem, and further studies are needed to identify an antibiotic to associate with gentamicin for an efficient dual ALBC against Gram-negative bacteria.<\/jats:p>","DOI":"10.3390\/antibiotics11020137","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T08:37:18Z","timestamp":1642754238000},"page":"137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Prophylactic Antibiofilm Activity of Antibiotic-Loaded Bone Cements against Gram-Negative Bacteria"],"prefix":"10.3390","volume":"11","author":[{"given":"Andr\u00e9a","family":"Cara","sequence":"first","affiliation":[{"name":"Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69007 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3082-7001","authenticated-orcid":false,"given":"Tristan","family":"Ferry","sequence":"additional","affiliation":[{"name":"Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69007 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Lyon, France"},{"name":"Service de Maladies Infectieuses, H\u00f4pital de la Croix-Rousse, Hospices Civils de Lyon, 69002 Lyon, France"},{"name":"Centre Interr\u00e9gional de R\u00e9f\u00e9rence des Infections Ost\u00e9o-Articulaires Complexes (CRIOAc Lyon), Hospices Civils de Lyon, 69002 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Laurent","sequence":"additional","affiliation":[{"name":"Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69007 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Lyon, France"},{"name":"Centre Interr\u00e9gional de R\u00e9f\u00e9rence des Infections Ost\u00e9o-Articulaires Complexes (CRIOAc Lyon), Hospices Civils de Lyon, 69002 Lyon, France"},{"name":"Laboratoire de Bact\u00e9riologie, Institut des Agents Infectieux, H\u00f4pital de la Croix-Rousse, Hospices Civils de Lyon, 69002 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6780-9646","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Josse","sequence":"additional","affiliation":[{"name":"Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69007 Lyon, France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, 69100 Lyon, France"},{"name":"Centre Interr\u00e9gional de R\u00e9f\u00e9rence des Infections Ost\u00e9o-Articulaires Complexes (CRIOAc Lyon), Hospices Civils de Lyon, 69002 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"ref_1","unstructured":"Buechel, F.F., Femino, F.P., and D\u2019Alessio, J. (2004). Primary Exchange Revision Arthroplasty for Infected Total Knee Replacement: A Long-Term Study. Am. J. Orthop., 33."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1302\/0301-620X.97B10.36475","article-title":"The Management of an Infected Total Knee Arthroplasty","volume":"97-B","author":"Gehrke","year":"2015","journal-title":"Bone Jt. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1128\/CMR.00111-13","article-title":"Prosthetic Joint Infection","volume":"27","author":"Tande","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jinf.2020.12.010","article-title":"Scientific Committee for Complex Bone and Joint Infections Reference Centers (CRIOAc), on behalf of the CRIOAc network Epidemiology of Complex Bone and Joint Infections in France Using a National Registry: The CRIOAc Network","volume":"82","author":"Lemaignen","year":"2021","journal-title":"J. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"O911","DOI":"10.1111\/1469-0691.12649","article-title":"Gram-negative Prosthetic Joint Infection: Outcome of a Debridement, Antibiotics and Implant Retention Approach. A Large Multicentre Study","volume":"20","author":"Pigrau","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1086\/605593","article-title":"Gram-negative Prosthetic Joint Infections: Risk Factors and Outcome of Treatment","volume":"49","author":"Hsieh","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.arth.2011.03.044","article-title":"Prosthetic Joint Infection Caused by Gram-negative Organisms","volume":"26","author":"Zmistowski","year":"2011","journal-title":"J. Arthroplast."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jinf.2011.11.010","article-title":"Orthopaedic-Implant Infections by Escherichia Coli: Molecular and Phenotypic Analysis of the Causative Strains","volume":"64","author":"Corvec","year":"2012","journal-title":"J. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"148","DOI":"10.4103\/ortho.IJOrtho_66_18","article-title":"A Comparison of Bacterial Adhesion and Biofilm Formation on Commonly Used Orthopaedic Metal Implant Materials: An In Vitro Study","volume":"53","author":"Malhotra","year":"2019","journal-title":"Indian J. Orthop."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.3389\/fmicb.2019.01602","article-title":"Interaction Between Staphylococcal Biofilm and Bone: How Does the Presence of Biofilm Promote Prosthesis Loosening?","volume":"10","author":"Josse","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119","DOI":"10.5312\/wjo.v12.i3.119","article-title":"Dual Antibiotic Loaded Bone Cement in Patients at High Infection Risks in Arthroplasty: Rationale of Use for Prophylaxis and Scientific Evidence","volume":"12","author":"Berberich","year":"2021","journal-title":"World J. Orthop."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.5435\/JAAOS-D-17-00305","article-title":"Antibiotic-Laden Bone Cement in Primary and Revision Hip and Knee Arthroplasty","volume":"26","author":"Gandhi","year":"2018","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wall, V., Nguyen, T.-H., Nguyen, N., and Tran, P.A. (2021). Controlling Antibiotic Release from Polymethylmethacrylate Bone Cement. Biomedicines, 9.","DOI":"10.3390\/biomedicines9010026"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jot.2020.04.005","article-title":"Antibiotic Containing Bone Cement in Prevention of Hip and Knee Prosthetic Joint Infections: A Systematic Review and Meta-Analysis","volume":"23","author":"Sebastian","year":"2020","journal-title":"J. Orthop. Translat."},{"key":"ref_15","first-page":"7","article-title":"The Effect of Antibiotic-Loaded Bone Cement on Risk of Revision Following Hip and Knee Arthroplasty","volume":"103-B","author":"Burnand","year":"2020","journal-title":"Bone Jt. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.arth.2016.11.012","article-title":"Is the Commercial Antibiotic-Loaded Bone Cement Useful in Prophylaxis and Cost Saving After Knee and Hip Joint Arthroplasty? The Transatlantic Paradox","volume":"32","year":"2017","journal-title":"J. Arthroplast."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3973","DOI":"10.1016\/j.arth.2021.08.014","article-title":"Cement Loaded with High-Dose Gentamicin and Clindamycin Reduces the Risk of Subsequent Infection After One-Stage Hip or Knee Arthroplasty Exchange for Periprosthetic Infection: A Preliminary Study","volume":"36","author":"Jenny","year":"2021","journal-title":"J. Arthroplast."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"576231","DOI":"10.3389\/fmed.2020.576231","article-title":"Antibiotics in Bone Cements Used for Prosthesis Fixation: An Efficient Way to Prevent Staphylococcus aureus and Staphylococcus epidermidis Prosthetic Joint Infection","volume":"7","author":"Cara","year":"2020","journal-title":"Front. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1080\/08927019909378416","article-title":"Effect of Gentamicin Loaded PMMA Bone Cement on Staphylococcus aureus Biofilm Formation","volume":"14","author":"Poelstra","year":"1999","journal-title":"Biofouling"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1080\/000164700317362280","article-title":"Gentamicin Release from Polymethylmethacrylate Bone Cements and Staphylococcus aureus Biofilm Formation","volume":"71","author":"Belt","year":"2000","journal-title":"Acta Orthop. Scand."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"831","DOI":"10.3109\/00365540903186207","article-title":"Microbiology of the Infected Knee Arthroplasty: Report from the Swedish Knee Arthroplasty Register on 426 Surgically Revised Cases","volume":"41","author":"Johansson","year":"2009","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1302\/2046-3758.210.2000188","article-title":"Gentamicin in Bone Cement","volume":"2","author":"Chang","year":"2013","journal-title":"Bone Jt. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1128\/AAC.13.6.918","article-title":"Surveillance of Gentamicin-Resistant Gram-negative Bacilli in a General Hospital","volume":"13","author":"Kauffman","year":"1978","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1469-0691.1998.tb00669.x","article-title":"Resistance to Amikacin and Gentamicin among Gram-negative Bloodstream Isolates in a University Hospital between 1989 and 1994","volume":"4","author":"Harbarth","year":"1998","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.3389\/fmicb.2019.02522","article-title":"Synergistic Activity of Fosfomycin, Ciprofloxacin, and Gentamicin Against Escherichia coli and Pseudomonas aeruginosa Biofilms","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0167-7012(00)00122-6","article-title":"A Modified Microtiter-Plate Test for Quantification of Staphylococcal Biofilm Formation","volume":"40","author":"Stepanovic","year":"2000","journal-title":"J. Microbiol. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13040","DOI":"10.1038\/s41598-018-31437-y","article-title":"A Steam-Based Method to Investigate Biofilm","volume":"8","author":"Tasse","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jor.2019.11.034","article-title":"Gentamycin Elution from Polymethylmethacrylate and Bone Graft Substitute: Comparison between Commercially Available and Home-Made Preparations","volume":"19","author":"Karaglani","year":"2020","journal-title":"J. Orthop."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1007\/s11999-008-0203-x","article-title":"Copal Bone Cement Is More Effective in Preventing Biofilm Formation than Palacos R-G","volume":"466","author":"Ensing","year":"2008","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"ftz022","DOI":"10.1093\/femspd\/ftz022","article-title":"Fosfomycin Tromethamine Activity on Biofilm and Intracellular Bacterial Communities Produced by Uropathogenic Escherichia coli Isolated from Patients with Urinary Tract Infection","volume":"77","author":"Notejane","year":"2019","journal-title":"Pathog. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Robu, A., Antoniac, A., Grosu, E., Vasile, E., Raiciu, A.D., Iordache, F., Antoniac, V.I., Rau, J.V., Yankova, V.G., and Ditu, L.M. (2021). Additives Imparting Antimicrobial Properties to Acrylic Bone Cements. Materials, 14.","DOI":"10.3390\/ma14227031"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jackson, J., Lo, J., Hsu, E., Burt, H.M., Shademani, A., and Lange, D. (2021). The Combined Use of Gentamicin and Silver Nitrate in Bone Cement for a Synergistic and Extended Antibiotic Action against Gram-Positive and Gram-negative Bacteria. Materials, 14.","DOI":"10.3390\/ma14123413"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chen, I.-C., Su, C.-Y., Nien, W.-H., Huang, T.-T., Huang, C.-H., Lu, Y.-C., Chen, Y.-J., Huang, G.-C., and Fang, H.-W. (2021). Influence of Antibiotic-Loaded Acrylic Bone Cement Composition on Drug Release Behavior and Mechanism. Polymers, 13.","DOI":"10.3390\/polym13142240"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"L\u00fcdemann, M., Jakuscheit, A., Ewald, A., Fr\u00fchmann, L., H\u00f6lscher-Doht, S., Rudert, M., and von Hertzberg-Boelch, S.P. (2021). Influence of Tranexamic Acid on Elution Characteristics and Compressive Strength of Antibiotic-Loaded PMMA-Bone Cement with Gentamicin. Materials, 14.","DOI":"10.3390\/ma14195639"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/2\/137\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:05:05Z","timestamp":1760133905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/2\/137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,21]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["antibiotics11020137"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics11020137","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,21]]}}}