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Anaerobe 48 (2017) 56e58

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Anaerobe

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Case report First described case of prosthetic joint infection with disporicum

* Joseph A. McBride a, b, , Alana K. Sterkel c, William M. Rehrauer c, Jeannina A. Smith a a University of Wisconsin, Department of Medicine, United States b University of Wisconsin, Department of Pediatrics, United States c University of Wisconsin, Department of Pathology and Laboratory Medicine, United States article info abstract

Article history: An orthopedic hardware infection with Clostridium disporicum is described. C. disporicum is a gram Received 26 January 2017 positive anaerobic which can contain two subterminal spores. C. disporicum had not previously Received in revised form been reported in musculoskeletal infections. Gram stains demonstrating gram positive bacilli with two 9 June 2017 subterminal spores should alert practitioners to the possibility of C. disporicum infection. Accepted 30 June 2017 Published by Elsevier Ltd. Available online 1 July 2017

Keywords: Clostridium disporicum Septic arthritis Prosthetic joint infection Anaerobic infection Orthopedic surgical infections

1. Introduction resection of the right distal femur with placement of hinged total knee megaprosthesis for recurrent metastatic renal cell carcinoma Clostridium is a diverse genus that consists of over 150 species. of the femur. Clostridial species are gram-positive, sporulating, anaerobic bacilli The patient had been diagnosed with metastatic renal cell car- normally found among gut flora and soil. Spontaneous gas cinoma two years earlier following discovery of a lytic lesion in his gangrene or clostridial myonecrosis are particularly serious in- right femur. At that time he underwent removal of the soft tissue fections and can be associated with contaminated wounds. Clos- mass and prophylactic intramedullary nailing of the femur. His tridium disporicum was first isolated from rat intestinal flora in 1987 renal cell carcinoma was subsequently managed with laparoscopic [1]. Biochemical evaluation revealed C. disporicum to be a novel nephrectomy and radiation therapy. Despite the surgery and radi- species distinct from Clostridium oceanicum, a previously described ation, he developed recurrent carcinoma surrounding the intra- two-spore producing Clostridium species [1]. We report a case of medullary rod. Clostridium disporicum in a post-surgical hardware associated The 2016 intraoperative course for femoral resection and meg- infection. aprosthesis placement was uneventful. The original intramedullary rod was removed. He was placed on peri-operative parenteral 2. Case report for 72 h. His hospitalization was complicated by post- operative delirium and Clostridium difficile associated diarrhea. He In 2016, a 70 year old male with a history of diabetes mellitus, was ultimately discharged home 11 days following surgery. fi chronic kidney disease, and metastatic renal cell carcinoma pre- Following discharge, he remained asymptomatic over the rst fi sented with an acute onset of fevers, chills, and right thigh pain 17 ve days; however, on the sixth day he reported an abrupt onset of days after orthopedic surgery. He had recently undergone a radical high fevers, chills, and excruciating pain in his right thigh. Upon presentation, he had a temperature of 40.3 C, a heart rate of 115 beats per minute, a blood pressure of 148/85, and an oxygen * Corresponding author. University of Wisconsin, 600 Highland Avenue Madison, saturation of 93%. There was no erythema, drainage, or discharge WI 53792, United States. surrounding his surgical site. Laboratory evaluation yielded a white E-mail address: [email protected] (J.A. McBride). http://dx.doi.org/10.1016/j.anaerobe.2017.06.022 1075-9964/Published by Elsevier Ltd. J.A. McBride et al. / Anaerobe 48 (2017) 56e58 57

Fig. 1. Gram stains from bone biopsy demonstrating Clostridium disporicum with both one and two subterminal spores. blood cell count of 11.0 K/mL, an erythrocyte sedimentation rate inflammatory markers remained elevated (ESR: 120, CRP: 10). At (ESR) of 61 mm/h, and a C-reactive protein (CRP) of 20 mg/dL. Blood eight weeks, his inflammatory markers (ESR: 110, CRP: 6) cultures were obtained and he was started on levofloxacin. Due to continued to be high and oral 750 mg q 12hrs was concern for necrotizing fasciitis, he was brought to the operating added to the . At ten weeks, his inflammatory makers room where a large hematoma was encountered. The fascia decreased (ESR: 78, CRP: 1.4) allowing for discontinuation of appeared intact without evidence of necrosis. Cultures of the he- parenteral penicillin. Due to his retained prosthesis, continued matoma and fascia were obtained. Due to significant morbidity suppression was recommended. At follow up one associated with prosthesis removal, the hardware was retained. month later, he reported dysgeusia and lower extremity neuropa- Gram stain of both cultures revealed greater than 25 poly- thy. Metronidazole suppression was discontinued in favor of morphonuclear cells and many large gram positive rods; frequently 500 mg q 12hrs. At one year postoperatively, he remains with two subterminal spores (Fig. 1). He was placed on empiric on suppressive amoxicillin with no recurrence or post-infection treatment with / and parenteral vancomy- complications. cin. Due to high suspicion of clostridial infection, clindamycin was added to decrease toxin production. 3. Discussion Within two days, intra-operative cultures revealed a Clostridium species growing at 37 C on reducible blood agar in an anaerobic Clostridial infections produce a wide spectrum of clinical dis- environment with 10% CO2. Matrix assisted laser desorption/ioni- ease, many of which are can be life-threatening. While many zation time of flight (MALDI-TOF) identified the Clostridium species are common intestinal anaerobic flora in organism as Clostridium disporicum (Bruker biotyper, library humans, C. disporicum is rarely encountered. C. disporicum has been v5989). 16S ribosomal RNA bacterial identification was performed isolated from intestinal tract of Crohn's disease patients and con- via extraction of DNA from the cultured isolate through steps tributes to their abnormal microflora when compared to healthy using first lysozyme (Ready-Lyse Lysozyme Solution; Epicentre, hosts [2]. Primary bacteremia from C. disporicum was described in a Madison, WI) at room temperature, proteinase K at 56 C and finally 75 year old diabetic female following insertion of a ring pessary for lysis buffer at first 70 C and then subsequently 95 C incubations. management of uterine prolapse [3]. Intra-abdominal infection After a DNA purification step (Qiagen QIAamp DNA Mini Kit; Hil- caused by C. disporicum was reported in a 66 year old male den, Germany), 16S rRNA gene sequences, consisting of two over- following hemicolectomy for colon cancer [4]. Both reported cases lapping PCR products targeted by two sets of primers (50 F: ATR GTT required bacterial 16S rDNA sequencing for identification and TGA TCC TGG CTC A, 50 R: GGA CTA CCA GGG TAT CTA AT; 30 F: TGC neither documented the presence of two subterminal spores on CAG CAG CCG CGG TAA, 30 R: GGY TAC CTT GTT ACG ACT T), were gram stain [3,4]. In our case, identification was rapidly reached with ® ® real-time amplified on a LightCycler 480 using LightCycler 480 the use of MALDI-TOF and later confirmed with 16S ribosomal RNA High Resolution Master (HRM) Sybr reagents (Roche Applied Sci- bacterial identification. ence, Indianapolis, IN). PCR products were treated with shrimp Clostridial musculoskeletal infections are most commonly and exonuclease I and subsequently bidirec- associated with traumatic penetrating injury and can rapidly tionally sequenced on an Applied Biosystems 3500 (Thermo Fisher progress to fulminant necrotizing fasciitis [5]. Musculoskeletal in- Scientific, Waltham, MA). The generated DNA sequences were fections attributed to clostridial species will often present with aligned to databases of known bacterial sequences, such as erythema, warmth, tenderness, joint effusion and limited range of Greengenes (http://greengenes.lbl.gov/cgi-bin/nph-index.cgi). Re- movement. Infections can produce overt fascia necrosis and gross sults confirmed identification of C. disporicum with a 99% match. tissue destruction with or without subcutaneous gas. Our patient Antimicrobial susceptibility testing characterized the isolate as pan presented with high fevers alongside severe surgical site tender- susceptible with minimum inhibitory concentrations (MICs) of ness; however, he had no evidence of wound erythema nor frank penicillin 0.5, clindamycin 0.064, 0.064, metronidazole fasciitis intraoperatively. The absence of our patient's localized 0.25, moxifloxacin 0.5 and of 0.125. His were tissue destruction highlights the need for prompt evaluation, narrowed to penicillin G plus clindamycin. He was ultimately dis- recognition and surgical management of Clostridium musculoskel- charged on continuous penicillin G monotherapy dosed at 8 million etal infections. units every 24 h due to underlying renal disease. Hardware associated infections with clostridial species have Five weeks later his symptoms had improved but his been reported in association with malignancies and 58 J.A. McBride et al. / Anaerobe 48 (2017) 56e58 immunocompromised states [6,7]. The long term survival of clos- Conflicts of interest tridial spores makes eradication of hardware associated infections challenging. Our patient's persistently elevated inflammatory There are no conflicts of interest to disclose. makers, and improvement only after combining parenteral and oral fi treatments, underscore the dif culties in management of hardware References associated clostridial infections. In most cases, the preferred treatment is a 2-stage exchange arthroplasty which includes [1] N. Horn, Clostridium disporicum sp. nov., a Saccharolytic species able to form debridement, prosthesis removal, placement of - two spores per cell, isolated from a Rat cecum, Int. J. Syst. Bacteriol. 37 (1987) 398e401. impregnated spacer, parenteral antimicrobial therapy, and ulti- [2] I. Mangin, R. Bonnet, P. Seksik, L. Rigottier-Gois, M. Sutren, Y. Bounik, et al., mate revision [8]. In situations with high surgical morbidity, Molecular inventory of faecal microflora in patient swith Crohn's disease, FEMS another potential option is prosthesis retention via surgical Microbiol. Ecol. 50 (2004) 25e36. [3] P.C.Y. Woo, S.K.P. Lau, K.M. Chan, A.M.Y. Fung, B.S.F. Tang, K.Y. Yuen, Clostridium debridement in conjunction with chronic antibiotic suppression bacteraemia characterized by 16S ribosomal RNA gene sequencing, J. Clin. [8]. In our case, due to the femoral bone's preexisting damage from Pathol. 58 (2005) 301e307, 1. metastasis and radiation, alongside the surgical complexity of [4] C. Plassart, F. Maurvais, J. Heurte, J. Sautereau, C. Legeay, First case of intra- e megaprosthesis removal, retention of the hardware with chronic abdominal infection with Clostridium disporicum, Anaerobe 19 (2013) 77 78. [5] C. Gredlin, M. Silverman, M. Downey, Polymicrobail septic arthritis due to antibiotic suppression was selected. It is not clear why he failed Clostridium species: case report and review, Clin. Infect. Dis. 30 (2000) penicillin monotherapy yet seemed to improve with the addition of 590e594. metronidazole given the low MIC's of the organism. [6] S. Morshed, F. Malek, R. Silverstein, R. O'Donnell, Clostdirium cadaveris septic fi arthritis after total hip arthroplasty in a metastatic breast cancer patient, Previously, many Clostridium species were not identi able in J. Arthroplasty 22 (2007) 289e292. clinical laboratories [3]. With the advent of newer and more readily [7] A. Garcia-Jimenez, N. Prim, X. Crusi, N. Benito, Septic arthritis due to Clostridium available identification techniques such as bacterial 16S rDNA and ramosum, Semin. Arthritis Rheum. 45 (2016) 617e620. [8] D. Osmon, E. Berbari, A. Berendt, D. Lew, W. Zimmerli, J. Steckelberg, N. Rao, MALDI-TOF mass spectrometry, clinicians may become more W. Wilson, Diagnosis and management of prosthetic joint infection: clinical familiar with rarer Clostridium species including C. disporicum. practice guidelines by the infectious disease society of America, CID (2013) 56.