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First Case of Periprosthetic Joint Infection Due to Clostridioides Difficile in China Yang Song1, Hong Yi Shao1, Xiang Cheng2 and Yu Guo2*

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First Case of Periprosthetic Joint Infection Due to Clostridioides Difficile in China Yang Song1, Hong Yi Shao1, Xiang Cheng2 and Yu Guo2* Song et al. BMC Infectious Diseases (2021) 21:462 https://doi.org/10.1186/s12879-021-06171-y CASE REPORT Open Access First case of periprosthetic joint infection due to Clostridioides difficile in China Yang Song1, Hong Yi Shao1, Xiang Cheng2 and Yu Guo2* Abstract Background: Clostridioides difficile usually causes intestinal infections. However, a 75-year-old lady had a periprosthetic joint infection due to this microorganism. We report a C. difficile infection of a prosthetic hip joint. Such an infection is rarely reported around the world. Case presentation: The elder female patient presented with a 2-year history of right hip pain with movement restriction. Her right leg was shorter than another. The skin around the right hip joint was red and swollen without sinus. Her lab test result showed elevator ESR and CRP. Her X-ray film showed a massive bone defect. The patient had a total hip arthroplasty 16 years ago and had a revision 5 years ago. During this hospitalization, her cultures of the synovial fluid and tissue repeatedly grew C. difficile. She improved following two-stage revision surgery and antibiotic treatment. The patient has no recurrence of infection after a one-year follow-up. Conclusion: A rapid and accurate sample collection is significant for culture results, making an outstanding contribution to the successful treatment. Keywords: Periprosthetic joint infection, Clostridioides difficile, Antibiotic treatment, Case report Background difficile is well culturable. Only five cases [6–10]of Total hip arthroplasty (THA) is a very effective sur- PJI involving C. difficile have been reported in the lit- gery for the treatment of late-stage osteoarthritis. erature to date. Among them, two were ultimately re- However, periprosthetic joint infection (PJI) is a po- solved by amputation. To the best of our knowledge, tentially catastrophic complication that affects nearly no such cases have been reported in China. We 1 to 3% of patients who have undergone THA [1, 2]. herein report the first known case of PJI caused by C. Gram-positive cocci constitute more than two-thirds difficile after THA in China and describe the isolation of the pathogenic organisms in PJI; other cases in- technique and treatment of this microorganism. volve Gram-negative bacteria, fungi, or other organ- isms [3]. There are 35% [4, 5] of cases of prosthetic Case presentation joint infection without detection of the infectious A 75-year-old woman presented with a 2-year history of Clostridioides difficile agent. is a spore-forming, toxin- right hip pain with restriction of movement. She had producing Gram-positive anaerobe, which usually undergone right hip arthroplasty because of a traumatic causes intestinal infections, has rarely been reported fracture 16 years previously;5 years ago, she underwent a C. in cases of PJI. When anaerobic culture is applied, revision for joint pain and limit movement. She had no comorbidities. Her hip pain had recurred 2 years ago, * Correspondence: [email protected] and she was treated with second-generation cephalo- 2 Department of Microbiology and Molecule Laboratory, Jishuitan Hospital sporin for her symptoms (night pain, elevated and Fourth Medical College of Peking University, 31 East Street, Xinjiekou, Xicheng District, Beijing 100035, CN, China temperature, swollen area of the hip), and her erythro- Full list of author information is available at the end of the article cyte sedimentation rate (ESR) was 60 mm/h (normal © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Song et al. BMC Infectious Diseases (2021) 21:462 Page 2 of 5 range 0 ~ 10 mm/h), and her C-reactive protein (CRP) four blood culture vials (two aerobic and two anaerobic concentration was 304 mg/L (normal range 0 ~ 10 mg/ vials) and cultured them using an instrumented blood L). The lab test result came to normal, but the pain still culture system (BACTECTM FX 100, Becton, Dickinson existed after the antibiotic treatment. Her pain and dis- and Company, New Jersey, US). The two anaerobic cul- ability had increased during the most recent 2 months. ture vials exhibited growth at 44 and 62 h after inocula- The patient arrived at our hospital in a wheelchair. tion, respectively; we then performed a Gram stain of Physical examination showed that her right lower ex- the samples and found Gram-positive bacilli under mi- tremity was shortened and that her hip exhibited flexion croscopy (Fig. 2). Gray-white wet colonies of medium contracture; the skin around the hip joint was red, swol- size, round shape, and irregular edges were observed in len without sinus. Her preoperative ESR was 43 mm/h, the anaerobic medium after 24 h of incubation (Fig. 3). and her CRP was 20.4 mg/L. Before the first stage, the The organism was identified as C. difficile by matrix- X-ray film showed a massive bone defect of the proximal assisted laser desorption/ionization time-of-flight mass femur, making the leg shortened (Fig. 1a). spectrometry (MALDI-TOF MS, Bruker Corporation, Aspiration of the patient’s hip joint produced almost Nehren, Germany). Identification was confirmed by 16S 30 mL of synovial fluid. The synovial fluid examination rRNA sequencing. Polymerase chain reaction tested revealed a white cell count (WBC) of 7548/mm3 with a (Tsingke company, Beijing, China) positively for the polymorphonuclear neutrophil (PMN) percentage of tcdA and tcdB genes of C. difficile. Antimicrobial testing 77%. We inoculated samples of the synovial fluid into showed that the bacterium was sensitive to Fig. 1 X-ray films of this two-stage treatment. a: X-ray film of the patient before the first stage operation; b: X-ray film of the patient after the first stage operation; c: X-ray film of the patient before the second stage operation Song et al. BMC Infectious Diseases (2021) 21:462 Page 3 of 5 antimicrobial testing, metronidazole was selected for treatment. The patient was treated with intravenous metronidazole for 2 weeks postoperatively and oral metronidazole (400 mg three times a day) for another 4 weeks. She then underwent the second stage of hip re- construction after confirming that her laboratory param- eters were normal (CRP: 2.65 mg/L; ESR: 26 mm/h). We used a tumor prosthesis to reconstruct her femur bone defect. And we used augment to econstruct the acetabu- lar (Fig. 1c). We obtained intraoperative samples again to ensure that the infection was under control. We checked an intraoperative cell count (WBC: 247/mm3; PMN percentage: 7%). Cultures of all samples showed no growth, and the patient underwent another round of antibiotic treatment (2 weeks of intravenous metronida- zole and another 4 weeks of oral metronidazole, as be- fore). She returned for regular follow-ups. At her latest Fig. 2 Gram-stain, microscopic morphology of Clostridium follow-up, 1 year after the diagnosis of PJI due to C. diffi- difficile (1000×) cile, her right hip was pain-free, and the incision had healed without clinical signs of infection. metronidazole and vancomycin (Etest, BIOMERIEUX, Paris, France). Discussion and conclusions We performed a two-stage revision for treatment of Clostridioides difficile (previously termed Clostridium this patient. In the first stage, we removed the prosthesis difficile) is a pathogen that causes antibiotic-associated and performed thorough debridement; this was followed diarrhea and pseudomembranous colitis with clinical by the placement of a cement spacer mixed with vanco- manifestations of diarrhea, abdominal pain [11]. Signifi- mycin (Fig. 1b). We mixed 4 g vancomycin in 36 g ce- cant risk factors for developing C. difficile infection ment (PALACOS®R, Heraeus Medical GmbH, (CDI) include antibiotic use, older age, poor host im- Wehrheim, Germany). Intraoperative cultures of the mune function, proton pump inhibitor use, previous synovial fluid and tissue repeatedly grew C. difficile. The CDI, and diabetes [12]. However, few extraintestinal antimicrobial susceptibility results were unchanged from CDI cases have been reported, especially bone and joint the previous cultures. According to the results of infections such as septic arthritis, osteomyelitis, and PJI. To date, only five patients have been reported to have PJI due to C. difficile; among them, two ultimately re- quired amputation [6–10]. One of these cases was re- ported in 1995; a 16-year-old boy developed CDI after total knee arthroplasty in France and underwent leg am- putation 1 year later. The other case involved a 61-year- old woman in the United States; a strain of C. difficile was isolated from tissue and fluid aspirated from her knee. The patient underwent an above-knee amputation 3 months later. In such cases, the reason for treatment failure is speculated to be associated with bacterial viru- lence and high antibiotic resistance. We have summa- rized all previously reported cases in Table 1.
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