Email updates

Keep up to date with the latest news and content from BMC Research Notes and BioMed Central.

Open Access Case Report

Clostridium difficile 027-associated pseudomembranous colitis after short-term treatment with cefuroxime and cephalexin in an elderly orthopedic patient: a case report

Kirstine Kobberøe Søgaard*, Tove Ejlertsen and Henrik Carl Schønheyder

Author Affiliations

Department of Clinical Microbiology, Aalborg Hospital, Aarhus University Hospital, Mølleparkvej 10 6 Sal, Aalborg DK- 9000, Denmark

For all author emails, please log on.

BMC Research Notes 2012, 5:609  doi:10.1186/1756-0500-5-609

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1756-0500/5/609


Received:27 June 2012
Accepted:15 October 2012
Published:31 October 2012

© 2012 Søgaard et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Clostridium difficile ribotype 027 has become increasingly prevalent in European countries. The clinical picture varies from self-limiting diarrhea to pseudomembranous colitis with toxic megacolon and ultimately death. Use of antibiotics is the principal risk factor; others include comorbidity, advanced age and hospitalization. However even with extensive knowledge of risk factors, it remains difficult to define “minimum risk,” as illustrated by the following case.

Case presentation

An 80-year-old Danish man in good health was hospitalized for a penetrating knee injury. He received 5 days of intravenous cefuroxime after surgical revision and was discharged with oral cephalexin. Post-discharge he suffered from abdominal discomfort and was readmitted with ileus 4 days after discharge, i.e. 10 days after initiation of antibiotic treatment. His condition deteriorated, and pseudomembranous colitis was diagnosed. Due to lack of response to vancomycin and metronidazole, a total colectomy was performed. Stool cultures were positive for CD 027.

Conclusion

Short-term use of cephalosporins may have induced CD 027 infection, and the patient’s age was the only identifiable risk factor for the fulminant course. Thus, even short-term prophylactic treatment with cephalosporins cannot be considered entirely safe.

Keywords:
Clostridium difficile; Ribotype 027; Pseudomembranous colitis; Cefuroxime; Cephalexin

Background

The increasing incidence and severity of Clostridium difficile (CD) infections is becoming a major clinical concern impacting public health. The clinical picture varies from self-limiting diarrhea to pseudomembranous colitis with toxic megacolon and ultimately death. CD is an important cause of hospital-acquired as well as healthcare-associated disease [1]; furthermore, the incidence of community-associated disease tends to reach levels equal to hospital-acquired disease [2]. In Denmark, colitis caused by CD infection has increased markedly among hospitalized patients over a 10 year period [3], and since 2009 when registering of subtypes began, the number of infections with ribotype 027 has doubled [4]. In a European laboratory survey of CD patients, the proportion of ribotype 027 was 5% [5].

Previous use of antibiotics is the most important risk factor for CD infection [6], particularly the use of cephalosporins [7] and flouroquinolones [8]. The risk is highest during or within the first month after antibiotic use [9]. Other established risk factors include comorbidity, advanced age and immunosuppression [5]. CD infection can also occur among “low-risk” populations (i.e., young people, people without underlying illness, people not exposed to hospitals or antimicrobials) [2], but people in good health are generally not affected by serious CD infection. Those with serious CD infection often have a high degree of comorbidity and long exposure to antibiotics [10]. Only a few case reports indicate that grave CD 027 infections can also occur in patients without significant comorbidity [11,12]. To emphasize the risk of fulminant pseudomembranous colitis (PMC) associated with CD 027, we report a case in a patient with modest comorbidity given short-term cephalosporin treatment.

Case presentation

An 80-year-old Danish man was admitted to hospital because of a 2-day history of increasing abdominal discomfort and constipation. Ten days earlier he had been hospitalized and treated for a penetrating knee injury, and had received a 5-day course of intravenous cefuroxime. Baseline comorbidity consisted of essential hypertension, mild sequelae after a minor stroke, and prostate cancer without proven dissemination. Previous surgical procedures were limited to appendectomy for perforated appendicitis 3 years earlier. The patient’s regular medications were bicalutamide, solifenacin, tamsulosin, simvastatin, losartan and clopidogrel, medications not known to be related to Clostridium difficile infection. While walking in the countryside, he had been hit by a small piece of metal from an agricultural machine. The object was removed surgically from the knee joint, and a ruptured collateral ligament was resutured. He was treated prophylactically with IV dicloxacillin 2 g at admission and IV cefuroxime 1.5 g during operation, followed by 750 mg q.i.d. for 5 days postoperatively. He was discharged on day 6 with oral cephalexin 1 g t.i.d (5 weeks’ treatment was scheduled). At the time of readmission (day 10), he was constipated and suffered from increasing abdominal discomfort, but he was clinically stabile, body temperature 36.9°C, serum C-reactive protein 296 mg/L (<10 mg/L), and white blood cell count 10.6 *109/L (<10.0 *109/L). However, his condition deteriorated rapidly to severe sepsis with high fever, hypotension and renal failure, and he was transferred to the intensive care unit. A CT scan of the abdomen revealed colitis, and sigmoidoscopy showed PMC affecting the distal colon up to the left colic flexure (Figure  1). Treatment with oral vancomycin and metronidazole was commenced, but repeated CT scans showed progression to the transverse and ascending colon. Four days after initiation of vancomycin and metronidazole (day 14 after surgery and initiation of cephalosporin treatment), a total colectomy was performed that left the patient with a permanent ileostomy. Stool culture was positive for CD 027, with genes for toxin A, toxin B and binary toxin.

thumbnailFigure 1. The endoscopic examination revealed an intestinal mucosa covered by adherent yellow-white plaques forming pseudomembranes.

Methods

Stool samples were cultured on ChromID C. difficile agar (bioMérieux, Marcy l’Etoil, France) in an atmosphere composed of 86% N2, 7% H2 and 7% CO2 at 37°C for 48 hours. Isolates of C. difficile were characterized by PCR ribotyping, toxin gene profiling, and deletion studies undertaken by the National Reference Laboratory for Enteropathogenic Bacteria at Statens Serum Institut, Copenhagen, Denmark.

Discussion

The majority of patients infected with CD 027 will suffer mild to severe diarrhea, whereas a few cases will proceed to PMC with toxic megacolon, sepsis and a possible fatal outcome. Cephalosporin use is associated with an increased risk of CD infection, and 3rd generation cephalosporins are considered to have the highest impact on intestinal bacterial flora because an active metabolite is secreted into small intestine via the gallbladder [9]. However, a growing body of evidence shows that also 1st and 2nd generation cephalosporins (i.e. cephalexin and cefuroxime) increase the risk of CD infection [13-15]. Cefuroxime is, however, by some, considered to be safe when used prophylactically or therapeutically in orthopedic surgery [16,17]. Characterization of the risk factors for fulminant manifestation of the disease is sparse. A prospective study including 1,008 Canadian patients with CD infection found that age was associated with a severe outcome when the infection was due to CD 027 [18]. A retrospective cohort study of 2,334 hospitalized patients with CD colitis in the United States found immunosuppression and recent comprehensive surgical procedures to be common predisposing conditions for colectomy; yet none of the patients undergoing colectomy had had orthopedic surgery [19]. On this basis, we cautiously conclude that the short-term use of cephalosporins induced CD 027 infection in our patient, and that his advanced age was the main risk factor for the fulminant progression.

Conclusion

We present a case of fulminant PMC associated with CD 027 in an elderly patient with only modest comorbidity who received a short course of dicloxacillin, cefuroxime, and cephalexin subsequent to a surgical revision of a knee injury. Apart from advanced age there was no underlying condition that explained the grave outcome in this patient. This finding further supports the overall principal of antimicrobial stewardship, which specifies to reduce inappropriate and excessive use of prophylactic cefuroxime and cephalexin.

Consent

Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Abbreviations

CD: Clostridium Difficile; PMC: PseudoMembranous Colitis; q.i.d.: quater in die (4 times a day); t.i.d.: ter in die (3 times a day).

Competing interests

The authors declare that they have no competing interests, and that they received no funding.

Authors' contributions

KKS drafted the manuscript. HCS and TEJ critically revised the manuscript. All authors read and approved the final manuscript.

Acknowledgements

We thank Saulius Palubinskas, Department of Surgery, Hjørring Hospital, for supplying the illustration, and Edwin Stanton Spencer for language editing.

References

  1. Price MF, Dao-Tran T, Garey KW, Graham G, Gentry LO, Dhungana L, Dupont HL: Epidemiology and incidence of Clostridium difficile-associated diarrhoea diagnosed upon admission to a university hospital.

    J Hosp Infect 2007, 65(1):42-46. PubMed Abstract | Publisher Full Text OpenURL

  2. Kuntz JL, Chrischilles EA, Pendergast JF, Herwaldt LA, Polgreen PM: Incidence of and risk factors for community-associated Clostridium difficile infection: a nested case–control study.

    BMC Infect Dis 2011, 11:194. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  3. Søes L, Mølbak K, Strøbæk S, Truberg Jensen K, Torpdahl M, Persson S, Kemp M, Olsen KE: The emergence of Clostridium difficile PCR ribotype 027 in Denmark – a possible link with the increased consumption of fluoroquinolones and cephalosporins? [http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19176] webcite

    Euro Surveil 2009, 14(15):pii=19176. OpenURL

  4. Olsen KEP, Jensen JN, Torpdahl M, Kjerulf A, Mølbak K: [http:/ / www.ssi.dk/ ~/ media/ Indhold/ EN%20-%20engelsk/ EPI-NEWS/ 2012/ pdf/ EPI-NEWS%20-%202012%20-%20No%207-8. ashx] webcite

    Clostridium difficile 2009-2011. Epinews; 2012, No.7/8. OpenURL

  5. Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, Monnet DL, van Dissel JT, Kuijper EJ, ECDIS Study Group: Clostridium difficile infection in Europe: a hospital-based survey.

    Lancet 2011, 377(9759):63-73. PubMed Abstract | Publisher Full Text OpenURL

  6. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH, Society for Healthcare Epidemiology of America; Infectious Diseases Society of America: : Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA).

    Infect Control Hosp Epidemiol 2010, 31(5):431-55. PubMed Abstract | Publisher Full Text OpenURL

  7. Nelson DE, Auerbach SB, Baltch AL, Desjardin E, Beck-Sague C, Rheal C, Smith RP, Jarvis WR: Epidemic Clostridium difficile-associated diarrhea: role of second and third-generation cephalosporins.

    Infect Control Hosp Epidemiol 1994, 15:88-94. PubMed Abstract | Publisher Full Text OpenURL

  8. Pépin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Authier S, Leblanc M, Rivard G, Bettez M, Primeau V, Nguyen M, Jacob CE, Lanthier L: Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec.

    Clin Infect Dis 2005, 41:1254-60. PubMed Abstract | Publisher Full Text OpenURL

  9. Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ: Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics.

    J Antimicrob Chemother 2012, 67(3):742-8. PubMed Abstract | Publisher Full Text OpenURL

  10. Byrn JC, Maun DC, Gingold DS, Baril DT, Ozao JJ, Divino CM: Predictors of mortality after colectomy for fulminant Clostridium difficile colitis.

    Arch Surg 2008, 143:150-154.

    discussion 155

    PubMed Abstract | Publisher Full Text OpenURL

  11. Candiotto A, Pascoli I, Gritti A, Busato E, Dal Pozzo G: Toxic megacolon complicating a Clostridium difficile infection in a pregnant woman.

    J Med Microbiol 2010, 59(Pt 1):124-6. PubMed Abstract | Publisher Full Text OpenURL

  12. Ingebretsen A, Hansen G, Harmanus C, Kuijper EJ: First confirmed cases of Clostridium difficile PCR ribotype 027 in Norway. [http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=8011] webcite

    Euro Surveill 2008, 13(2):pii=8011. OpenURL

  13. Baxter R, Ray GT, Fireman BH: Case–control study of antibiotic use and subsequent Clostridium difficile-associated diarrhea in hospitalized patients.

    Infect Control Hosp Epidemiol 2008, 29(1):44-50. PubMed Abstract | Publisher Full Text OpenURL

  14. Al-Obaydi W, Smith CD, Foguet P: Changing prophylactic antibiotic protocol for reducing Clostridium difficile-associated diarrhoeal infections.

    J Orthop Surg (Hong Kong) 2010, 18(3):320-3. OpenURL

  15. Al-Eidan FA, McElnay JC, Scott MG, Kearney MP: Clostridium difficile-associated diarrhoea in hospitalised patients.

    J Clin Pharm Ther 2000, 25(2):101-9. PubMed Abstract | Publisher Full Text OpenURL

  16. Jenkins PJ, Teoh K, Simpson PM, Dave J, Simpson AH, Breusch S: Clostridium difficile in patients undergoing primary hip and knee replacement.

    J Bone Joint Surg Br 2010, 92(7):994-8. PubMed Abstract | Publisher Full Text OpenURL

  17. Vesteinsdottir I, Gudlaugsdottir S, Einarsdottir R, Kalaitzakis E, Sigurdardottir O, Bjornsson ES: Risk factors for Clostridium difficile toxin-positive diarrhea: a population-based prospective case–control study.

    Eur J Clin Microbiol Infect Dis 2012.

    Epub ahead of print

    OpenURL

  18. Miller M, Gravel D, Mulvey M, Taylor G, Boyd D, Simor A, Gardam M, McGeer A, Hutchinson J, Moore D, Kelly S: Health care-associated Clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality.

    Clin Infect Dis 2010, 50(2):194-201. PubMed Abstract | Publisher Full Text OpenURL

  19. Dallal RM, Harbrecht BG, Boujoukas AJ, Sirio CA, Farkas LM, Lee KK, Simmons RL: Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications.

    Ann Surg 2002, 235(3):363-72. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL