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BMJ Case Rep. 2010; 2010: bcr06.2009.2017.
Published online 2010 January 13. doi:  10.1136/bcr.06.2009.2017
PMCID: PMC3029095
Unusual presentation of more common disease/injury

Toxic megacolon from hypervirulent Clostridium difficile infection (ribotype 027) following elective total knee replacement: an emerging challenge in modern health care


We present a rare case of community acquired (presenting in hospital on the day of admission or within 48 h of admission) Clostridium difficile infection (CDI) with the hypervirulent (ribotype 027) strain causing toxic megacolon in a patient, diagnosed on the third postoperative day following an elective total knee replacement. The patient did not have any of the commonly reported risk factors for CDI. The source of sepsis was initially presumed to be the operated prosthetic joint, and this caused a delay in the correct diagnosis and institution of appropriate antimicrobial treatment which may have contributed to a poorer outcome. This case highlights the risk of patients arriving from the community manifesting life threatening CDI in the hospital.


Clostridium difficile infection (CDI) is an important healthcare associated cause of morbidity and death all over the world.1 CDI presents as diarrhoea, abdominal cramps, and fever with leucocytosis commonly. Pancolitis with toxic megacolon is a very severe form of the disease with nearly 30% mortality.2 The well known risk factors for CDI are broad spectrum antibiotic use, elderly patients, prior hospitalisation, gastrointestinal surgery, immunosuppressant therapy, and more recently exposure to proton pump inhibitors,2 although the exact mechanism is still debated. Incidence of CDI outside healthcare settings is an emerging concern.3,4 In recent decades, hypervirulent strains of C difficile, like ribotype 027, are being diagnosed with increasing frequency across the world, thereby increasing the incidence of fulminant CDI.5 CDI in orthopaedic patients is not uncommon following prophylactic antibiotic use6,7 but this rarely is a cause of morbid sepsis within 48–72 h after surgery. We describe the case of a patient admitted for an elective total knee replacement and was diagnosed with toxic megacolon 48–72 h after surgery with significant morbidity following a C difficile infection of the hypervirulent ribotype 027 strain. In this report the peculiarities in presentation and the difficulty in diagnosis of this case are discussed.

Case presentation

A 63-year-old Caucasian male was admitted for an elective total knee replacement of his right knee for osteoarthritis. He had a history of myoclonus and was allergic to non-steroidal anti-inflammatory drugs (NSAIDs). There was no history of recent prior hospitalisation (in the past year) or antibiotic intake. An ex-professional footballer, he had smoked 10 cigarettes per day for the past 20 years until 3 years before admission. He was classified as an ASA grade 2. The patient underwent a primary right cemented total knee replacement under general anaesthesia the next day as planned. He received three doses of intravenous co-amoxiclav (amoxicillin–clavulanic acid) 1.2 g perioperatively as surgical prophylaxis and the tourniquet time was 1 h 35 min.

Postoperatively he was on fentanyl PCA (patient controlled analgesia). He had one spike of temperature within 24 h of surgery at 38.1°C which settled spontaneously. On the second postoperative day the temperature rose to 39.2°C. A septic screen (including blood cultures) was performed. As he had some basal crepitations he received intravenous co-amoxiclav for a chronic obstructive pulmonary disease (COPD) related chest infection. On physiotherapy, the patient was complaining of significant pain in the right knee on flexion. The next morning he was acutely unwell with a pulse rate of 110/min, a blood pressure of 115/70 mm Hg and a respiratory rate of 24/min. He received intravenous piperacillin/tazobactam instead of co-amoxiclav for septicaemia as the C reactive protein concentration was 407 mg/l and the white blood cell count (WCC) was 19.8×109/l. His abdomen was distended with absent bowel sounds but the patient was passing flatus. Blood gases revealed only mild metabolic acidosis. He was started on oral metronidazole as per our hospital policy for a possible CDI, after a stool sample was obtained and an erect abdominal x-ray performed (fig 1). The general surgeon on call reviewed the patient and diagnosed a probable postoperative ileus. He opined that the right prosthetic knee joint was septic as it was painful and inflamed. This was compounded by the mild hypokalaemia the patient had on the first postoperative day which was corrected within 24 h. In the next few hours he deteriorated rapidly with a pulse rate of 140/min, blood pressure of 80/50 mm Hg, and decreasing urinary output. He was intubated and transferred to intensive care as his Glasgow Coma Scale (GCS) dropped to 8 and the airway was at risk.

Figure 1
Abdominal x-ray showing multiple gas filled large and small bowel loops measuring up to 4 cm in diameter.

The patient had an urgent computed tomography (CT) scan with intravenous contrast (fig 2) which showed severe dilatation of the transverse colon with toxic megacolon features without perforation. Later an emergency laparotomy revealed a toxic megacolon involving the whole of the transverse colon and most of the descending colon. A subtotal colectomy with an ileostomy was performed. The stool sample result received next day was positive for C difficile toxin and on further analysis was identified as belonging to ribotype 027.

Figure 2
An axial computed tomography abdominal section showing a fistulous, thickened and oedematous large bowel wall with a transverse colon diameter of 6 cm.

Outcome and follow-up

The patient was fit for discharge 3 months following the knee replacement. He was last reviewed 12 months after surgery for his right total knee replacement which is painless and has 0–110° of flexion and a WOMAC score of 96 with an excellent result.


CDI is one of the main causes of healthcare associated infection and rising health care costs worldwide.1 The risk factors have been clearly highlighted in many previous studies of which prior hospital admission and antibiotic use are the most common. C difficile is an anaerobic Gram positive bacillus and its presentation can range from asymptomatic carrier state to life threatening pseudomembranous enterocolitis.2

Fulminant CDI is increasing with an overall rise in mortality from CDI. The importance of patients developing CDI in the community is increasingly recognised even in healthy young individuals.3,8 Occurrences of CDI outside health care settings and in the paediatric population are the new emerging challenges.4 The infection is also occurring in the absence of the traditional risk factors. Use of the common gastric pH altering drugs and drugs delaying gut motility have been implicated more strongly in recent times,4 although the exact mechanism is unclear.

The pathological process of CDI involves colonisation with spores which germinate and multiply in the colon. The two toxins produced by C difficile are toxins A and B which induce damage to the gut tissue and disrupt the cell-to-cell tight junctions.9 A new subtype of polymerase chain reaction (PCR) ribotype 027 has been isolated first in Canada, North America and later in Europe.10 In the UK, over 50% of CDI isolates typed by the reference laboratory between 1995 and 2003 were of ribotype 01.5,10 An analysis of 881 C difficile isolates from all over England in 2007 revealed ribotype 027 strain in 25% of them.11 Newer studies specifically showed patients have a longer interval between admission and onset of diarrhoea and follows increased exposure to quinolones with ribotype 027 subtype. It is characterised by the production of binary toxin in addition to toxins A and B, needs a small inoculum, and has higher sporulation levels.5

The incidence of pseudomembranous colitis is up to 3% and is on the rise with the rapidly increasing prevalence of CDI.4 Toxic megacolon is characterised by the presence of toxicity and colonic distension (>6 cm). In a cohort of 70 patients with toxic megacolon, CDI accounted for 30% of cases.12 This is a highly lethal condition with a mortality nearing 30% and the management is urgent subtotal colectomy to prevent perforation and sepsis.12

Elective orthopaedic patients contracting CDI is not uncommon; this has been described traditionally after using cephalosporins and clindamycin for surgical prophylaxis and with prolonged period of prophylaxis.7 There is a positive correlation between the delay in diagnosis and the severity of illness.6 A severe infection in patients with CDI is described as a fever of 38.5°C and a WCC of 17.5×109/l, or a WCC of 20×109/l alone.6 In the previous series, the mean duration of onset of diarrhoea in elective surgical patients was 7 days.6,7 Our patient had no risk factors and developed ileus and diarrhoea within 48 h of surgery. The postoperative pain and inflammation following knee replacement misdirected the clinician towards a septic knee, thereby delaying diagnosis and increasing the severity of sepsis. The patient was hypokalaemic at 3.0 mmol on the first postoperative day, prompting the surgeons to assume this was an ileus. The patient was started on metronidazole but he did not improve, and the fact that his subtype was of the hypervirulent ribotype 027 explains the rapid deterioration of his general condition.

This is a rare occurrence in a relatively healthy patient admitted for a routine total knee replacement. CDI is a differential diagnosis even in patients without risk factors, who are admitted from the community and develop sepsis within 48–72 h of elective surgery. Prompt suspicion, sampling, medical management and involvement of surgeons with critical care is essential, even with which this group has poor outcomes. The in-hospital mortality rate following fulminant CDI is around 50%.13 In spite of nationwide guidelines, alerts, infection control policies and barrier nursing, C difficile is a new emerging threat all over the world.

Learning points

  • Clostridium difficile infection (CDI) can be contracted in the community and outside all healthcare settings without the risk factors.
  • Clostridium difficile ribotye 027 is a hypervirulent strain which causes fatal CDI more frequently.
  • Life threatening CDI is possible in an apparently healthy patient admitted in the hospital for a routine procedure within 48–72 h.
  • Toxic megacolon should be suspected without any delay, as the extent of delay significantly affects the prognosis.
  • Regular metronidazole administration may not be enough; oral vancomycin is more likely to stop the progress of fulminant CDI if infection with ribotype 027 is suspected.


We would like to thank the patient for consenting for the publication of such an important and educational report


Competing interests: None.

Patient consent: Patient/guardian consent was obtained for publication.


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