{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:13:55Z","timestamp":1792707235442,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>The treatment of periprosthetic joint infections (PJI), and especially of re-infections, poses a highly complex problem in orthopaedic surgery. While fungal infections are rare, they present a special challenge. The therapy is often protracted and based on limited evidence. A total of 510 hip and knee revision surgeries were analysed for the occurrence of bacterial and fungal PJI. In patients with PJI, the duration of the hospital stay and the incidence of disarticulation of the infected joint were recorded. Out of the analysed revision arthroplasties, 43.5% were due to PJI. Monomicrobial infection occurred in 55.2%, dual microbial infection in 21.4%, and polymicrobial (\u22653 different bacterial or fungal species) infection in 17.2% of the cases. Overall, Candida species were detected in 12.4% cases. Candida albicans was the main fungal pathogen. In 6.9% of cases, disarticulation of the joint was the only option to control PJI. The detection of polymicrobial infection more than doubled in follow-up revisions and there was a strong association between detection of Candida infection and disarticulation (OR 9.39). The majority of fungal infections were mixed infections of bacteria and Candida albicans. The choice of a biofilm penetrating antimycotic, e.g., caspofungin, together with a sufficient standard procedure for detection and surgical treatment can help to control the infection situation. Fungal infection often proves to be more difficult to treat than anticipated and is more frequent than expected.<\/jats:p>","DOI":"10.3390\/jof7060404","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T13:15:15Z","timestamp":1621602915000},"page":"404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Periprosthetic Fungal Infections in Severe Endoprosthetic Infections of the Hip and Knee Joint\u2014A Retrospective Analysis of a Certified Arthroplasty Centre of Excellence"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9258-487X","authenticated-orcid":false,"given":"Andreas","family":"Enz","sequence":"first","affiliation":[{"name":"Orthopaedic Clinic and Policlinic, University Medicine Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8774-5950","authenticated-orcid":false,"given":"Silke C.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University Medicine Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Warnke","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ellenrieder","sequence":"additional","affiliation":[{"name":"Orthopaedic Clinic and Policlinic, University Medicine Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Mittelmeier","sequence":"additional","affiliation":[{"name":"Orthopaedic Clinic and Policlinic, University Medicine Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annett","family":"Klinder","sequence":"additional","affiliation":[{"name":"Orthopaedic Clinic and Policlinic, University Medicine Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"ref_1","first-page":"Doc17","article-title":"Two-Stage Revision of Implant-Associated Infections after Total Hip and Knee Arthroplasty","volume":"6","author":"Ellenrieder","year":"2011","journal-title":"GMS Krankenhhyg Interdiszip"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Natsuhara, K.M., Shelton, T.J., Meehan, J.P., and Lum, Z.C. (2018). Mortality During Total Hip Periprosthetic Joint Infection. J. Arthroplast.","DOI":"10.1016\/j.arth.2018.12.024"},{"key":"ref_3","first-page":"398","article-title":"Diagnosis of Periprosthetic Infection\u2014What\u2019s Obligation, What\u2019s Optional?","volume":"154","author":"Heller","year":"2016","journal-title":"Z. Orthop. Unfallchir."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S459","DOI":"10.1016\/j.arth.2018.09.031","article-title":"Hip and Knee Section, Treatment, Salvage: Proceedings of International Consensus on Orthopedic Infections","volume":"34","author":"Ghazavi","year":"2019","journal-title":"J. Arthroplasty"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.rbo.2016.09.001","article-title":"Hip Disarticulation\u2014Case Series Analysis and Literature Review","volume":"52","author":"Moura","year":"2017","journal-title":"Rev. Bras. Ortop."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Preobrazhensky, P.M., Bozhkova, S.A., Kazemirsky, A.V., Tikhilov, R.M., Kulaba, T.A., and Kornilov, N.N. (2019). Functional Outcome of Two-Stage Reimplantation in Patients with Periprosthetic Joint Infection after Primary Total Knee Arthroplasty. Int. Orthop.","DOI":"10.1007\/s00264-019-04296-z"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.knee.2018.04.004","article-title":"Efficacy of Antifungal-Impregnated Cement Spacer against Chronic Fungal Periprosthetic Joint Infections after Total Knee Arthroplasty","volume":"25","author":"Kim","year":"2018","journal-title":"Knee"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1080\/21505594.2018.1475798","article-title":"Biguanides Enhance Antifungal Activity against Candida Glabrata","volume":"9","author":"Xu","year":"2018","journal-title":"Virulence"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1099\/jmm.0.045054-0","article-title":"Candida Species: Current Epidemiology, Pathogenicity, Biofilm Formation, Natural Antifungal Products and New Therapeutic Options","volume":"62","author":"Sardi","year":"2013","journal-title":"J. Med. Microbiol."},{"key":"ref_10","first-page":"459","article-title":"Candidemia: Species Involved, Virulence Factors and Antimycotic Susceptibility","volume":"35","author":"Guglielminetti","year":"2012","journal-title":"New Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/s12178-018-9504-1","article-title":"Risk Factors and Treatment Options for Failure of a Two-Stage Exchange","volume":"11","author":"Fagotti","year":"2018","journal-title":"Curr. Rev. Musculoskelet. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1016\/j.arth.2018.03.003","article-title":"Periprosthetic Joint Infection with Fungal Pathogens","volume":"33","author":"Brown","year":"2018","journal-title":"J. Arthroplast."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lee, Y.R., Kim, H.J., Lee, E.J., Sohn, J.W., Kim, M.J., and Yoon, Y.K. (2018). Prosthetic Joint Infections Caused by Candida Species: A Systematic Review and a Case Series. Mycopathologia.","DOI":"10.1007\/s11046-018-0286-1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"114","DOI":"10.7150\/jbji.17699","article-title":"Candida Prosthetic Joint Infection. A Review of Treatment Methods","volume":"2","author":"Cobo","year":"2017","journal-title":"J. Bone Jt. Infect."},{"key":"ref_15","unstructured":"Groll, A.H., Buchheidt, D., Heinz, W., Bellmann, R., Cornely, O., H\u00f6hl, R., H\u00f6nigl, M., Kluge, S., Kurzai, O., and Lass-Fl\u00f6rl, C. (2020). S1 Leitlinie Diagnose und Therapie von Candida Infektionen: Gemeinsame Empfehlungen der Deutschsprachigen Mykologischen Gesellschaft (DMykG) und der Paul-Ehrlich-Gesellschaft f\u00fcr Chemotherapie (PEG) ICD 10: B37, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V."},{"key":"ref_16","unstructured":"Podbielski, A., Abele-Horn, M., Herrmann, M., Kniehl, E., Mauch, H., and R\u00fcssmann, H. (2014). MIQ 19: Mikrobiologische Diagnostik Der Arthritis Und Osteomyelitis, Urban & Fischer Verlag\/Elsevier."},{"key":"ref_17","unstructured":"Becker, K., Berner, R., Eckmann, C., Eiff, C., Hartinger, A., Kempf, V.A.J., K\u00fchn, J., Podbielski, A., Sunderk\u00f6tter, C.H., and Vogel, U. (2014). MIQ 18: Mikrobiologische Diagnostik Der Arthritis Und Osteomyelitis\u2014Ernster, Urban & Fischer Verlag\/Elsevier. [2nd ed.]."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"142","DOI":"10.2106\/JBJS.I.00574","article-title":"Microbiological, Clinical, and Surgical Features of Fungal Prosthetic Joint Infections: A Multi-Institutional Experience","volume":"91","author":"Azzam","year":"2009","journal-title":"J. Bone Jt. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1302\/0301-620X.94B5.28125","article-title":"Fungal Peri-Prosthetic Joint Infection after Primary Total Knee Replacement","volume":"94","author":"Hwang","year":"2012","journal-title":"J. Bone Jt. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"732.e1","DOI":"10.1016\/j.cmi.2016.05.004","article-title":"Time Trends in the Aetiology of Prosthetic Joint Infections: A Multicentre Cohort Study","volume":"22","author":"Benito","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1007\/s00402-020-03335-4","article-title":"Difficult to Treat: Are There Organism-Dependent Differences and Overall Risk Factors in Success Rates for Two-Stage Knee Revision?","volume":"140","author":"Faschingbauer","year":"2020","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fernandes, A. (2013). The Microbiological Profiles of Infected Prosthetic Implants with an Emphasis on the Organisms Which Form Biofilms. JCDR.","DOI":"10.7860\/JCDR\/2013\/4533.2732"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00402-008-0679-6","article-title":"Neutrophils in Frozen Section and Type of Microorganism Isolated at the Time of Resection Arthroplasty for the Treatment of Infection","volume":"129","author":"Bori","year":"2009","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_24","first-page":"411","article-title":"Infection Following Total Knee Arthroplasty: Prevention and Management","volume":"61","author":"Garvin","year":"2012","journal-title":"Instr. Course Lect."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Enz, A., Becker, J., Warnke, P., Prall, F., Lutter, C., Mittelmeier, W., and Klinder, A. (2020). Increased Diagnostic Certainty of Periprosthetic Joint Infections by Combining Microbiological Results with Histopathological Samples Gained via a Minimally Invasive Punching Technique. J. Clin. Med., 9.","DOI":"10.3390\/jcm9103364"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.jmii.2018.08.011","article-title":"The Incidence Rate, Trend and Microbiological Aetiology of Prosthetic Joint Infection after Total Knee Arthroplasty: A 13 Years\u2019 Experience from a Tertiary Medical Center in Taiwan","volume":"51","author":"Wang","year":"2018","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"890","DOI":"10.3109\/00365548.2010.498023","article-title":"Candida Prosthetic Infections: Case Series and Literature Review","volume":"42","author":"Dutronc","year":"2010","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3109\/17453674.2013.859422","article-title":"2-Stage Revision Recommended for Treatment of Fungal Hip and Knee Prosthetic Joint Infections: An Analysis of 164 Patients, 156 from the Literature and 8 Own Cases","volume":"84","author":"Kuiper","year":"2013","journal-title":"Acta Orthop."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3134","DOI":"10.1093\/jac\/dku225","article-title":"Clinical Validation of a Multiplex Real-Time PCR Assay for Detection of Invasive Candidiasis in Intensive Care Unit Patients","volume":"69","author":"Meije","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_30","first-page":"1","article-title":"Nosocomial Candidiasis: Antifungal Stewardship and the Importance of Rapid Diagnosis","volume":"54","author":"Pfaller","year":"2015","journal-title":"Med. Myco."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Clancy, C.J., and Nguyen, M.H. (2018). Non-Culture Diagnostics for Invasive Candidiasis: Promise and Unintended Consequences. J. Fungi, 4.","DOI":"10.3390\/jof4010027"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1111\/j.1365-2672.2006.03187.x","article-title":"Surface Charge Influences Enterococcal Prevalence in Mixed-Species Biofilms","volume":"102","author":"Pothoven","year":"2007","journal-title":"J. Appl. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1574-6968.2009.01668.x","article-title":"Cross-Kingdom Interactions: Candida Albicans and Bacteria","volume":"299","author":"Shirtliff","year":"2009","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Morales, D.K., and Hogan, D.A. (2010). Candida Albicans Interactions with Bacteria in the Context of Human Health and Disease. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000886"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1099\/mic.0.062109-0","article-title":"Staphylococcus Aureus Adherence to Candida Albicans Hyphae Is Mediated by the Hyphal Adhesin Als3p","volume":"158","author":"Peters","year":"2012","journal-title":"Microbiology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1016\/j.cub.2014.08.057","article-title":"Anaerobic Bacteria Grow within Candida Albicans Biofilms and Induce Biofilm Formation in Suspension Cultures","volume":"24","author":"Fox","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kong, E.F., Tsui, C., Kuchar\u00edkov\u00e1, S., Andes, D., Van Dijck, P., and Jabra-Rizk, M.A. (2016). Commensal Protection of Staphylococcus Aureus against Antimicrobials by Candida Albicans Biofilm Matrix. mBio, 7.","DOI":"10.1128\/mBio.01365-16"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Koo, H., Andes, D.R., and Krysan, D.J. (2018). Candida-Streptococcal Interactions in Biofilm-Associated Oral Diseases. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007342"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1128\/AAC.04650-14","article-title":"Fungal \u03b2-1,3-Glucan Increases Ofloxacin Tolerance of Escherichia Coli in a Polymicrobial E. Coli\/Candida Albicans Biofilm","volume":"59","author":"Tan","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1128\/AAC.46.6.1773-1780.2002","article-title":"Antifungal Susceptibility of Candida Biofilms: Unique Efficacy of Amphotericin B Lipid Formulations and Echinocandins","volume":"46","author":"Kuhn","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Persyn, A., Rogiers, O., Brock, M., Vande Velde, G., Lamkanfi, M., Jacobsen, I.D., Himmelreich, U., Lagrou, K., Van Dijck, P., and Kuchar\u00edkov\u00e1, S. (2019). Monitoring of Fluconazole and Caspofungin Activity against In Vivo Candida Glabrata Biofilms by Bioluminescence Imaging. Antimicrob. Agents Chemother., 63.","DOI":"10.1128\/AAC.01555-18"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4333","DOI":"10.1128\/IAI.71.8.4333-4340.2003","article-title":"Mechanism of Fluconazole Resistance in Candida Albicans Biofilms: Phase-Specific Role of Efflux Pumps and Membrane Sterols","volume":"71","author":"Mukherjee","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_44","unstructured":"Enz, A., Mueller, S., Mittelmeier, W., and Klinder, A. Severe polymicrobial and fungal periprosthetic osteomyelitis persisting after hip disarticulations treated with caspofungin in risk patients. In Review."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rimke, C., Enz, A., Bail, H.J., Heppt, P., Kladny, B., von Lewinski, G., Lohmann, C.H., Osmanski-Zenk, K., Haas, H., and Mittelmeier, W. (2020). Evaluation of the Standard Procedure for the Treatment of Periprosthetic Joint Infections (PJI) in Germany\u2014Results of a Survey within the EndoCert Initiative. BMC Musculoskelet. Disord., 21.","DOI":"10.1186\/s12891-020-03670-y"},{"key":"ref_46","first-page":"5623","article-title":"Fungal Periprosthetic Joint Infection in Total Knee Arthroplasty: A Systematic Review","volume":"7","author":"Jakobs","year":"2015","journal-title":"Orthop. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1093\/cid\/cis200","article-title":"Performance of Candida Real-Time Polymerase Chain Reaction, \u03b2-D-Glucan Assay, and Blood Cultures in the Diagnosis of Invasive Candidiasis","volume":"54","author":"Nguyen","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1136\/jclinpath-2017-204692","article-title":"Diagnostic Accuracy of Fungal PCR and \u03b2-d-Glucan for Detection of Candidaemia: A Preliminary Evaluation","volume":"71","author":"McKeating","year":"2018","journal-title":"J. Clin. Pathol."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/7\/6\/404\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:05:25Z","timestamp":1760162725000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/7\/6\/404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,21]]},"references-count":48,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["jof7060404"],"URL":"https:\/\/doi.org\/10.3390\/jof7060404","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,21]]}}}