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Rare extraintestinal infection caused by toxin-producing Clostridium difficile
Anaerobe 16 (2010) 301–303
Contents lists available at ScienceDirect
Anaerobe journal homepage: www.elsevier.com/locate/anaerobe
Clinical Microbiology
Rare extraintestinal infection caused by toxin-producing Clostridium difficile Edit Urba´n a, *, Gabriella Terhes a, Attila Markotics b, Jo´zsef So´ki a, Elizabeth Nagy a a b
Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, Hungary Department of Traumatology, Faculty of Medicine, University of Szeged, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history: Received 16 July 2009 Received in revised form 9 September 2009 Accepted 8 October 2009 Available online 14 October 2009
Toxigenic Clostridium difficile is a well known cause of antibiotic-associated diarrhea mainly among hospitalized patients, at the same time we have little information about extraintestinal infections caused by this bacterium. We report here on rare extraintestinal infection caused by toxigenic C. difficile: 31-year-old male, accident victim was admitted to the hospital because of polytrauma. Microbiological examination of the pus revealed a toxin-producing C. difficile as an etiologic factor of this infection. Empiric antibiotic treatment with cefuroxime had been administered right after the positive microbiological result. On the basis of antibiotic susceptibility testing, the isolated strain was susceptible to most antimicrobials, except from cefoxitin, thus cefuroxime was changed to imipenem. Ó 2009 Elsevier Ltd. All rights reserved.
Keywords: Clostridium difficile Extraintestinal infection Anaerobic cultivation Toxin detection
1. Case report A 31-year old, otherwise healthy, male patient with normal immune status was admitted to the Traumatology Department, University of Szeged, after injuring his right lower limb due to potato harvesting machine. In the middle third of his lower leg, laterally and medially, 10-cm transfacial, ragged torn wounds were present. On the right dorsal surface of his foot at the level of the tarsometatarsal joint, a deep wound extending to the bone surface and displaying a destroyed Lisfranc joint was visible, therefore an extensive wound debridement was performed. This wound was grossly contaminated and required bone and soft tissue debridement, partial removal of the navicular bone, and subchondral resection of the cuneiform bone. In the surgical intervention, wound situated medially was thoroughly irrigated and debrided; lateral wound after exploration showed penetration into the peroneal and extensor compartments. In this wound, complete destruction of the tissue was noticed and extensive debridement was performed again. The limb was properly stabilized with an external fixator. On the second postoperative day, bullae formation and local erythema around the lateral wound were noticed, thus wound revision was performed and sample for microbiological investigation was taken. Two days later, local erythema was noticed
* Corresponding author. Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, H-6725 Szeged, Semmelweis u 6, Hungary. Tel./fax: þ36 62 545712. E-mail address: [email protected] (E. Urba´n). 1075-9964/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.anaerobe.2009.10.004
again in the lateral wounds, and necrectomy was performed, the clinicians attempted to reduce the size of the wound defect, but they were unable to do so without excessive tension. Medial wound appeared clean in this time. In the patient’s medical history, neither febrile period nor diarrhea was recorded in the postoperative period in the hospital and later at home. First intraoperative swab samples of wounds for microbiological investigation were taken in the operation room, while the second was collected two days later from the pus of the lateral wound and sent to the microbiological laboratory, where the samples were suspended in 1 ml reduced BHI broth (Brain Heart Infusion broth pH 7.2; Oxoid, Basingstoke, United Kingdom) and after gentle dispersion, these suspensions were plated immediately on selective and non-selective media. Columbia agar base (Oxoid, Basingstoke, United Kingdom) supplemented with 5% (v/v) cattle blood, hemin and vitamin K1 was used to quantify the total cultivable facultative and anaerobic bacterial flora. For aerobic bacteria, the plates were incubated at 37 C in a 5% CO2-containing environment for 48 h. For the isolation of anaerobic organisms, cultures were set up and incubated in an atmosphere of 90% N2, 5% H2 and 5% CO2 in an anaerobic environment (Bactron from Sheldon Manufacturing Inc., Cornelius, Oregon, USA) for 2 days at 37 C. The results from Gram-staining and the atmospheric growth requirements of each colony type were used to determine the additional biochemical tests required to identify the isolates. API 20A (bioMe´rieux, S.A., Marcy l’Etoile, France) tests were used to identify anaerobic bacteria. Culture from the lateral wound sample showed the presence of a high CFU/ml of a Clostridium. difficile strain by anaerobic incubation and few colonies of
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E. Urba´n et al. / Anaerobe 16 (2010) 301–303
Bacillus subtilis strain by aerobic incubation, the second sample contained only the same C. difficile strain, but the CFU/ml was lower. The following MIC values of C. difficile strain were determined by Etest method (ABbiodisk Solna, Sweden): penicillin 4 mg/L, amoxycillin/clavulanic acid 8 mg/L, metronidazole 0.5 mg/L, imipenem 1 mg/L, meropenem 2 mg/L, cefoxitin 64 mg/L, and clindamycin 8 mg/L. To determine the toxigenic status of the isolated C. difficile strain, cytotoxicity test on HeLa cell line and VIDAS TOX AB (bioMe´rieux, S.A., Marcy l’Etoile, France) test were performed from broth culture [1]. The presence of major toxin coding genes (tcdA and tcdB) and binary toxin genes were investigated for by PCR [2,3,4]. By cytotoxicity assay, and the following neutralization with C. difficile goat antitoxin serum, which neutralizes both toxin A and toxin B, the isolated strain proved to be toxin-positive, this finding was supported by the results of tcdA and tcdB PCR too. No binary toxin gene was detected in this strain. On the basis of the identification and antibiotic susceptibility testing results, prophylactic antibiotic (cefuroxime) was changed to therapeutic imipenem, daily operating theatre lavage and irrigation were performed. After the second surgical procedure and appropriate antibiotic therapy, no clinical signs of acute inflammation were observed, and the patient was completely recovered without permanent injury. 2. Discussion and conclusions C. difficile is well recognized as the main etiologic agent of antibiotic-associated- and pseudomembranous colitis, and implicated as the cause of 20 to 25% of cases of antibiotic-associated diarrhea [5]. This nosocomial pathogen has been responsible for numerous recent hospital-based epidemics [6,7], and its importance and incidence seem to be increasing worldwide [8]. In contrast to its propensity for causing intestinal infections, very few cases of C. difficile bacteremia or other extraintestinal illness have been reported [9,10,11], these occurred mainly when a severe underlying disease was present. In most cases of septicemia, the source of infections has been found to be the gastrointestinal tract, as suggested by isolation of C. difficile as a member of mixed flora, with other intestinal bacteria [12–16]. A recent publication by Wolf et al. of this topic identified only 17 published cases of extraintestinal C. difficile (ECD) infection [17]; when this organism was isolated mostly from pleural fluid, peritoneal fluid, blood, and bone, as well as splenic, vaginal, and thigh abscesses. Only in three cases, ECD was reported in association with the presence of C. difficile toxin in the stool. Another review showed also 17 patients with ECD [18]: C. difficile isolates in 12 patients were obtained from structures or fluids anatomically close to the colon and included the following infections: peritonitis in five cases (three primary and two secondary), intra-abdominal abscesses in three patients and abdominal wound infections in four cases, while infections in the other five patients were not in anatomic vicinity of the colon. They included one case with a brain abscess, two episodes of bacteremia and two cases of foot infections (one chronic osteomyelitis). In all but one case, C. difficile isolation was obtained as part of a polymicrobial flora. Isolates were frequently nontoxigenic and extraintestinal infections occurred without concomitant diarrhea or prior antimicrobial therapy. Out of 17 patients, eight died and nine survived. Death could not be directly attributed to C. difficile in any of the cases. The other review of the literature by Bedimo and Weinstein [19] showed 59 cases of extraintestinal C. difficile infections that present in three main forms: bacteremia with or without focal infection, intra-abdominal infections, and extra-abdominal abscesses. C. difficile was isolated in pure culture only in a minority (32%) of cases, and recovered in a context of polymicrobial infection (bacteremia or abscess) in 40 (68%) of the 59 cases. In the latter context, it may not be the primary pathogen; C. difficile is thought to
potentate infections by other organisms or enhance the pathogenesis of other bacteria in mixed infections [20]. Although the majority of patients had underlying illnesses (e.g., malignancy and chronic renal disease), trauma, or surgery, at least 30% had no identifiable predisposing condition. It is postulated that C. difficile may gain access to the abdominal cavity or bloodstream following a breakdown of the mucosal barrier. However, gastrointestinal abnormality was either absent (27%) or not reported (31%) in a substantial proportion of patients. Diarrhea was absent in at least 32% of the patients with extraintestinal infection, and 37% of patients died. Assays for toxin, the main virulence factor for C. difficile, have rarely been done in patients with extraintestinal C. difficile infections, while in other publications, some cases have been caused by nontoxigenic strains. Stieglbauer et al. [21] reported that the level of immunoglobulin (Ig) G antibodies to toxin A was 20-fold higher, whereas that of IgA antibodies was threefold higher, in a patient who developed a splenic abscess due to C. difficile infection, as compared with the mean levels in sera from 14 patients who had C. difficile diarrhea only. The effect of these naturally occurring antibodies on the natural history of the infection is uncertain [22,23]. A case of post-traumatic wound infection in immunocompetent, young and otherwise healthy trauma patient caused by C. difficile is reported nowadays by Deptula et al. a 31-years old female, a car accident victim, was admitted to the hospital because of polytrauma after open reduction and internal fixation of the supracondylar femoral fracture by means of DCS (Dynamic Condylar Screw) system a purulent fistula occurred [24]. The microbiological examination of the pus revealed C. difficile as a single etiologic factor of this infection. The empirical antibiotic treatment with cefazoline and metronidazole had been administered right after the surgery, but was found to be ineffective. The strain isolated from the patient was sensitive to most antimicrobials except from clindamycin and amoxicillin/clavulanic acid had been chosen for the guided therapy. Such treatment combined with the removal of DCS system brought desirable effect. The isolation of C. difficile outside the intestinal tract is uncommon, its clinical significance should be interpreted with caution [25]. In our case, the patient was not immunocompromised; he had no history of diabetes, malignancy and gastrointestinal disorders. He injured his leg harvesting potato, thus his lacerated wounds were grossly contaminated by soil. This was suggested by the fact that B. subtilis, which is characteristic soil bacteria, was isolated from the wound, too. At the same time, it is well known that the natural habitat of the spores of C. difficile is the soil, sand, wastewater, the bowel of various vertebrates, and hospital environment, thus the presence of this bacterium in the wound was not surprising, however infections caused by this bacterium are quite rare. In conclusion, extraintestinal C. difficile is a rare and probably underdiagnozed condition that is associated with high mortality. Its true prevalence, pathogenesis, and risk factors require further studies.
References [1] Terhes G, Urba´n E, So´ki J, Kanjo AH, Nagy E. Community-acquired Clostridium difficile diarrhea caused by binary toxin, toxin A and toxin B gene-positive isolates in Hungary. J Clin Microbiol 2004;42:4316–8. [2] Kato H, Kato N, Watanabe K, Iwai N, Nakamura H, Yamamoto T, et al. Identification of toxin A-negative, toxin B-positive Clostridium difficile by PCR. J Clin Microbiol 1998;36:2178–82. [3] Kato N, Ou Chin-Yih, Kato H, Bartley S, Brown VK, Dowell VRJR, et al. Identification of toxigenic Clostridium difficile by the polymerase chain reaction. J Clin Microbiol 1991;29:33–7. [4] Stubbs S, Rupnik M, Gibert M, Brazier J, Duerden B, Popoff M. Production of actin-specific ADP-ribosyltransferase (binary toxin) by strains of C. difficile. FEMS Microbiol Lett 2000;186:307–12.
E. Urba´n et al. / Anaerobe 16 (2010) 301–303 [5] Viscidi R, Willey S, Bartlett JG. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 1981;81:5–9. [6] Degl’Innocenti R, De Santis M, Berdondini I, Dei R. Outbreak of Clostridium difficile diarrhoea in an orthopaedic unit: evidence by phage-typing for crossinfection. J Hosp Infect 1989;13:309–14. [7] Nolan NP, Kelly CP, Humphreys JF, Cooney C, O’Connor R, Walsh TN, et al. An epidemic of pseudomembranous colitis: importance of person to person spread. Gut 1987;28:1467–73. [8] Samore MH, DeGirolami PC, Tlucko A, Lichtenberg DA, Melvin ZA, Karchmer AW. Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994;18:181–7. [9] Ge´rard M, Defresne N, Van der Auwera P, Meunier F. Polymicrobial septicemia with Clostridium difficile in acute diverticulitis. Eur J Clin Microbiol Infect Dis 1989;8:300–2. [10] Rampling A, Warren RE, Bevan PC, Hogarth CE, Swirski D, Hayhoe Fg J. Clostridium difficile in a haematological malignancy. J Clin Pathol 1985;38:445–51. [11] Saginur R, Fogel R, Begin L, Cohen B, Mendelson J. Splenic abscess due to Clostridium difficile. J Infect Dis 1983;147:1105. [12] Silva J. Clostridium difficile. Nosocomial infections-still lethal and persistent. Infect Control Hosp Epidemiol 1994;15:368–70. [13] Onderdonk AB, Allen SD. Clostridium. In: Murray PR, et al., editors. Manual of clinical microbiology. Washington, D.C: American Society for Microbiology; 1995. p. 574–86. [14] Samore MH, De Girolami PC, Tiucko A, Lichtenberg DA, Melvin ZA, Karchmer AN. Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994;18:181–7. [15] Simor AE, Yake SL, Tsimidis K. Infection due to Clostridium difficile among elderly residents of a long-term care facility. Clin Infect Dis 1993;17:672–8.
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[16] Feldman RJ, Kallich M, Weinstein MP. Bacteremia due to Clostridium difficile: case report and review of extraintestinal C. difficile infections. Clin Infect Dis 1995;20:1560–2. [17] Wolf LE, Sherwood L, Gorbach H, Granowitz EV. Extraintestinal Clostridium difficile: 10 Years’ Experience at a Tertiary-Care Hospital. Mayo Clin Proc 1998;73:943–7. [18] Garcia-Lechuz JM, Hernangomez S, Juan RS, Pelaez T, Alcala L, Bouza E. Extraintestinal infections caused by Clostridium difficile. Clin Microbiol Infect 2001;7:453–7. [19] Bedimo R, Weinsten J. Recurrent extraintestinal Clostridum difficile infection. Am J Med 2003;9:770–1. [20]. Brook I, Walker RI. Pathogenicity of Clostridium species with other bacteria in mixed infections. J Infect 1986;13:245–53. [21] Stieglbauer KT, Gruber SA, Johnson S. Elevated serum antibody response to toxin A following splenic abscess due to Clostridium difficile. Clin Infect Dis 1995;20:160–2. [22] Warny M, Vaerman J-P, Avesani V. Human antibody response to Clostridium difficile and correlation with other typing systems. J Clin Microbiol 1994;31:1870–5. [23] Johnson S, Gerding D, Janoff E. Systemic and mucosal antibody responses to toxin A in patients with Clostridium difficile. J Infect Dis 1992;166:1287–94. [24] Deptula A, Kruszyn´ska E, Mikucka A, Gospodarek E, Olszewski K, Kruczyn´ski J, Matewski D. Toxin A-producing Clostridium difficile as an aetiologic factor of post-traumatic wound infection. J Med Microbiol 2009;58:963–4. [25] Bhargava A, Sen P, Swaminathan A, Ogbolu C, Chechko S, Stone F. Rapidly Progressive Necrotizing Fascitis and Gangrene Due to Clostridium difficile: Case Report. Clin Infect Dis 2000;30:954–5.
Contents lists available at ScienceDirect
Anaerobe journal homepage: www.elsevier.com/locate/anaerobe
Clinical Microbiology
Rare extraintestinal infection caused by toxin-producing Clostridium difficile Edit Urba´n a, *, Gabriella Terhes a, Attila Markotics b, Jo´zsef So´ki a, Elizabeth Nagy a a b
Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, Hungary Department of Traumatology, Faculty of Medicine, University of Szeged, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history: Received 16 July 2009 Received in revised form 9 September 2009 Accepted 8 October 2009 Available online 14 October 2009
Toxigenic Clostridium difficile is a well known cause of antibiotic-associated diarrhea mainly among hospitalized patients, at the same time we have little information about extraintestinal infections caused by this bacterium. We report here on rare extraintestinal infection caused by toxigenic C. difficile: 31-year-old male, accident victim was admitted to the hospital because of polytrauma. Microbiological examination of the pus revealed a toxin-producing C. difficile as an etiologic factor of this infection. Empiric antibiotic treatment with cefuroxime had been administered right after the positive microbiological result. On the basis of antibiotic susceptibility testing, the isolated strain was susceptible to most antimicrobials, except from cefoxitin, thus cefuroxime was changed to imipenem. Ó 2009 Elsevier Ltd. All rights reserved.
Keywords: Clostridium difficile Extraintestinal infection Anaerobic cultivation Toxin detection
1. Case report A 31-year old, otherwise healthy, male patient with normal immune status was admitted to the Traumatology Department, University of Szeged, after injuring his right lower limb due to potato harvesting machine. In the middle third of his lower leg, laterally and medially, 10-cm transfacial, ragged torn wounds were present. On the right dorsal surface of his foot at the level of the tarsometatarsal joint, a deep wound extending to the bone surface and displaying a destroyed Lisfranc joint was visible, therefore an extensive wound debridement was performed. This wound was grossly contaminated and required bone and soft tissue debridement, partial removal of the navicular bone, and subchondral resection of the cuneiform bone. In the surgical intervention, wound situated medially was thoroughly irrigated and debrided; lateral wound after exploration showed penetration into the peroneal and extensor compartments. In this wound, complete destruction of the tissue was noticed and extensive debridement was performed again. The limb was properly stabilized with an external fixator. On the second postoperative day, bullae formation and local erythema around the lateral wound were noticed, thus wound revision was performed and sample for microbiological investigation was taken. Two days later, local erythema was noticed
* Corresponding author. Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, H-6725 Szeged, Semmelweis u 6, Hungary. Tel./fax: þ36 62 545712. E-mail address: [email protected] (E. Urba´n). 1075-9964/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.anaerobe.2009.10.004
again in the lateral wounds, and necrectomy was performed, the clinicians attempted to reduce the size of the wound defect, but they were unable to do so without excessive tension. Medial wound appeared clean in this time. In the patient’s medical history, neither febrile period nor diarrhea was recorded in the postoperative period in the hospital and later at home. First intraoperative swab samples of wounds for microbiological investigation were taken in the operation room, while the second was collected two days later from the pus of the lateral wound and sent to the microbiological laboratory, where the samples were suspended in 1 ml reduced BHI broth (Brain Heart Infusion broth pH 7.2; Oxoid, Basingstoke, United Kingdom) and after gentle dispersion, these suspensions were plated immediately on selective and non-selective media. Columbia agar base (Oxoid, Basingstoke, United Kingdom) supplemented with 5% (v/v) cattle blood, hemin and vitamin K1 was used to quantify the total cultivable facultative and anaerobic bacterial flora. For aerobic bacteria, the plates were incubated at 37 C in a 5% CO2-containing environment for 48 h. For the isolation of anaerobic organisms, cultures were set up and incubated in an atmosphere of 90% N2, 5% H2 and 5% CO2 in an anaerobic environment (Bactron from Sheldon Manufacturing Inc., Cornelius, Oregon, USA) for 2 days at 37 C. The results from Gram-staining and the atmospheric growth requirements of each colony type were used to determine the additional biochemical tests required to identify the isolates. API 20A (bioMe´rieux, S.A., Marcy l’Etoile, France) tests were used to identify anaerobic bacteria. Culture from the lateral wound sample showed the presence of a high CFU/ml of a Clostridium. difficile strain by anaerobic incubation and few colonies of
302
E. Urba´n et al. / Anaerobe 16 (2010) 301–303
Bacillus subtilis strain by aerobic incubation, the second sample contained only the same C. difficile strain, but the CFU/ml was lower. The following MIC values of C. difficile strain were determined by Etest method (ABbiodisk Solna, Sweden): penicillin 4 mg/L, amoxycillin/clavulanic acid 8 mg/L, metronidazole 0.5 mg/L, imipenem 1 mg/L, meropenem 2 mg/L, cefoxitin 64 mg/L, and clindamycin 8 mg/L. To determine the toxigenic status of the isolated C. difficile strain, cytotoxicity test on HeLa cell line and VIDAS TOX AB (bioMe´rieux, S.A., Marcy l’Etoile, France) test were performed from broth culture [1]. The presence of major toxin coding genes (tcdA and tcdB) and binary toxin genes were investigated for by PCR [2,3,4]. By cytotoxicity assay, and the following neutralization with C. difficile goat antitoxin serum, which neutralizes both toxin A and toxin B, the isolated strain proved to be toxin-positive, this finding was supported by the results of tcdA and tcdB PCR too. No binary toxin gene was detected in this strain. On the basis of the identification and antibiotic susceptibility testing results, prophylactic antibiotic (cefuroxime) was changed to therapeutic imipenem, daily operating theatre lavage and irrigation were performed. After the second surgical procedure and appropriate antibiotic therapy, no clinical signs of acute inflammation were observed, and the patient was completely recovered without permanent injury. 2. Discussion and conclusions C. difficile is well recognized as the main etiologic agent of antibiotic-associated- and pseudomembranous colitis, and implicated as the cause of 20 to 25% of cases of antibiotic-associated diarrhea [5]. This nosocomial pathogen has been responsible for numerous recent hospital-based epidemics [6,7], and its importance and incidence seem to be increasing worldwide [8]. In contrast to its propensity for causing intestinal infections, very few cases of C. difficile bacteremia or other extraintestinal illness have been reported [9,10,11], these occurred mainly when a severe underlying disease was present. In most cases of septicemia, the source of infections has been found to be the gastrointestinal tract, as suggested by isolation of C. difficile as a member of mixed flora, with other intestinal bacteria [12–16]. A recent publication by Wolf et al. of this topic identified only 17 published cases of extraintestinal C. difficile (ECD) infection [17]; when this organism was isolated mostly from pleural fluid, peritoneal fluid, blood, and bone, as well as splenic, vaginal, and thigh abscesses. Only in three cases, ECD was reported in association with the presence of C. difficile toxin in the stool. Another review showed also 17 patients with ECD [18]: C. difficile isolates in 12 patients were obtained from structures or fluids anatomically close to the colon and included the following infections: peritonitis in five cases (three primary and two secondary), intra-abdominal abscesses in three patients and abdominal wound infections in four cases, while infections in the other five patients were not in anatomic vicinity of the colon. They included one case with a brain abscess, two episodes of bacteremia and two cases of foot infections (one chronic osteomyelitis). In all but one case, C. difficile isolation was obtained as part of a polymicrobial flora. Isolates were frequently nontoxigenic and extraintestinal infections occurred without concomitant diarrhea or prior antimicrobial therapy. Out of 17 patients, eight died and nine survived. Death could not be directly attributed to C. difficile in any of the cases. The other review of the literature by Bedimo and Weinstein [19] showed 59 cases of extraintestinal C. difficile infections that present in three main forms: bacteremia with or without focal infection, intra-abdominal infections, and extra-abdominal abscesses. C. difficile was isolated in pure culture only in a minority (32%) of cases, and recovered in a context of polymicrobial infection (bacteremia or abscess) in 40 (68%) of the 59 cases. In the latter context, it may not be the primary pathogen; C. difficile is thought to
potentate infections by other organisms or enhance the pathogenesis of other bacteria in mixed infections [20]. Although the majority of patients had underlying illnesses (e.g., malignancy and chronic renal disease), trauma, or surgery, at least 30% had no identifiable predisposing condition. It is postulated that C. difficile may gain access to the abdominal cavity or bloodstream following a breakdown of the mucosal barrier. However, gastrointestinal abnormality was either absent (27%) or not reported (31%) in a substantial proportion of patients. Diarrhea was absent in at least 32% of the patients with extraintestinal infection, and 37% of patients died. Assays for toxin, the main virulence factor for C. difficile, have rarely been done in patients with extraintestinal C. difficile infections, while in other publications, some cases have been caused by nontoxigenic strains. Stieglbauer et al. [21] reported that the level of immunoglobulin (Ig) G antibodies to toxin A was 20-fold higher, whereas that of IgA antibodies was threefold higher, in a patient who developed a splenic abscess due to C. difficile infection, as compared with the mean levels in sera from 14 patients who had C. difficile diarrhea only. The effect of these naturally occurring antibodies on the natural history of the infection is uncertain [22,23]. A case of post-traumatic wound infection in immunocompetent, young and otherwise healthy trauma patient caused by C. difficile is reported nowadays by Deptula et al. a 31-years old female, a car accident victim, was admitted to the hospital because of polytrauma after open reduction and internal fixation of the supracondylar femoral fracture by means of DCS (Dynamic Condylar Screw) system a purulent fistula occurred [24]. The microbiological examination of the pus revealed C. difficile as a single etiologic factor of this infection. The empirical antibiotic treatment with cefazoline and metronidazole had been administered right after the surgery, but was found to be ineffective. The strain isolated from the patient was sensitive to most antimicrobials except from clindamycin and amoxicillin/clavulanic acid had been chosen for the guided therapy. Such treatment combined with the removal of DCS system brought desirable effect. The isolation of C. difficile outside the intestinal tract is uncommon, its clinical significance should be interpreted with caution [25]. In our case, the patient was not immunocompromised; he had no history of diabetes, malignancy and gastrointestinal disorders. He injured his leg harvesting potato, thus his lacerated wounds were grossly contaminated by soil. This was suggested by the fact that B. subtilis, which is characteristic soil bacteria, was isolated from the wound, too. At the same time, it is well known that the natural habitat of the spores of C. difficile is the soil, sand, wastewater, the bowel of various vertebrates, and hospital environment, thus the presence of this bacterium in the wound was not surprising, however infections caused by this bacterium are quite rare. In conclusion, extraintestinal C. difficile is a rare and probably underdiagnozed condition that is associated with high mortality. Its true prevalence, pathogenesis, and risk factors require further studies.
References [1] Terhes G, Urba´n E, So´ki J, Kanjo AH, Nagy E. Community-acquired Clostridium difficile diarrhea caused by binary toxin, toxin A and toxin B gene-positive isolates in Hungary. J Clin Microbiol 2004;42:4316–8. [2] Kato H, Kato N, Watanabe K, Iwai N, Nakamura H, Yamamoto T, et al. Identification of toxin A-negative, toxin B-positive Clostridium difficile by PCR. J Clin Microbiol 1998;36:2178–82. [3] Kato N, Ou Chin-Yih, Kato H, Bartley S, Brown VK, Dowell VRJR, et al. Identification of toxigenic Clostridium difficile by the polymerase chain reaction. J Clin Microbiol 1991;29:33–7. [4] Stubbs S, Rupnik M, Gibert M, Brazier J, Duerden B, Popoff M. Production of actin-specific ADP-ribosyltransferase (binary toxin) by strains of C. difficile. FEMS Microbiol Lett 2000;186:307–12.
E. Urba´n et al. / Anaerobe 16 (2010) 301–303 [5] Viscidi R, Willey S, Bartlett JG. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 1981;81:5–9. [6] Degl’Innocenti R, De Santis M, Berdondini I, Dei R. Outbreak of Clostridium difficile diarrhoea in an orthopaedic unit: evidence by phage-typing for crossinfection. J Hosp Infect 1989;13:309–14. [7] Nolan NP, Kelly CP, Humphreys JF, Cooney C, O’Connor R, Walsh TN, et al. An epidemic of pseudomembranous colitis: importance of person to person spread. Gut 1987;28:1467–73. [8] Samore MH, DeGirolami PC, Tlucko A, Lichtenberg DA, Melvin ZA, Karchmer AW. Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994;18:181–7. [9] Ge´rard M, Defresne N, Van der Auwera P, Meunier F. Polymicrobial septicemia with Clostridium difficile in acute diverticulitis. Eur J Clin Microbiol Infect Dis 1989;8:300–2. [10] Rampling A, Warren RE, Bevan PC, Hogarth CE, Swirski D, Hayhoe Fg J. Clostridium difficile in a haematological malignancy. J Clin Pathol 1985;38:445–51. [11] Saginur R, Fogel R, Begin L, Cohen B, Mendelson J. Splenic abscess due to Clostridium difficile. J Infect Dis 1983;147:1105. [12] Silva J. Clostridium difficile. Nosocomial infections-still lethal and persistent. Infect Control Hosp Epidemiol 1994;15:368–70. [13] Onderdonk AB, Allen SD. Clostridium. In: Murray PR, et al., editors. Manual of clinical microbiology. Washington, D.C: American Society for Microbiology; 1995. p. 574–86. [14] Samore MH, De Girolami PC, Tiucko A, Lichtenberg DA, Melvin ZA, Karchmer AN. Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994;18:181–7. [15] Simor AE, Yake SL, Tsimidis K. Infection due to Clostridium difficile among elderly residents of a long-term care facility. Clin Infect Dis 1993;17:672–8.
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