Campylobacter colitis leads to toxic megacolon and multiple organ failure

Abstract

A 58-year-old woman presented to the emergency department in a district general hospital with severe abdominal pain and diarrhoea, after collapsing at home. She was admitted to the intensive care unit (ICU) in septic shock, and with acute kidney injury. An initial CT scan was suggestive of colitis. She was treated for suspected gastroenteritis and her microbiology results showed Campylobacter coli as the causative organism. She failed to respond to antibiotics, and underwent serial contrast CTs which showed no progression of colitis. Colonoscopy performed on day 10 of her admission, however, revealed fulminant colitis. After a multidisciplinary meeting among gastroenterologists, general surgeons and intensivists, the patient underwent total colectomy with ileostomy. She made a slow but steady recovery in ICU, and subsequently in the ward, and was discharged to a local community hospital for further rehabilitation.

Background

Campylobacter, a genus of Gram-negative bacteria, is the most common cause of food-borne illness in the UK; in 2017 alone, there were over 56 000 reported cases, with the age group most affected being those of 50–59 years old.¹ In a large study of patients infected with campylobacter, 93% were infected with Campylobacter jejuni and 7% with Campylobacter coli.² Chicken has been identified as the most likely causative source in 78% of cases of C. jejuni and 56% of C. coli.³ For approximately 80% of these patients, clinical presentation will be a short diarrhoeal illness followed by complete recovery within 1 week.⁴ We present a case where this typical clinical course was not followed, and our patient had a rare complication of Campylobacter infection, namely enterocolitis, leading to toxic megacolon, and requiring total colectomy. In a study of 70 patients in three centres, the main cause of toxic megacolon was ulcerative colitis in 32 patients (46%), followed by infectious colitis in 24 patients (34%), and ischaemic colitis in 8 patients (11%).⁵ To date there are only 13 published case reports of toxic megacolon caused by Campylobacter species, and of these reports only 7 required total colectomy.⁶ Toxic megacolon is defined as total or segmental colonic dilation in conjunction with severe systemic disturbance in the form of sepsis and organ dysfunction.⁷ Recognition and subsequent treatment of toxic megacolon must be prompt as associated mortality is high, and although initial management is supportive, early surgical involvement is essential. Indications for surgery include progressive colonic dilation, clinical deterioration and perforation.⁵ This case demonstrates the severity of morbidity that can be associated with this common pathogen, the importance of early involvement of a surgical team, and the benefits of optimising medical management in an intensive care setting where severe fluid and electrolyte disturbances can be swiftly managed.

Case presentation

A usually fit and well 58-year-old woman, with a medical history of coeliac disease and chronic bilateral upper limb pain, presented to the emergency department (ED) with severe diarrhoea and abdominal pain. Four days prior to presentation, she and her husband had eaten a take-away meal including chicken. Her husband had had diarrhoea and vomiting to a mild degree, and the patient herself had had some suprapubic pain and dysuria, with normal bowel movements. Her general practitioner had seen her the day prior to admission and treated her for a suspected urinary tract infection with nitrofurantoin. However, on the day of presentation, an ambulance was called to her house as she had collapsed and had been faecally incontinent with loose stools. She was found to be peripherally shut down with suspected peritonitis. On arrival to the ED, she had a blood pressure of 65/45 mm Hg, a heart rate of 116 beats/min and a temperature of 34.8°C. Her abdominal examination showed a distended abdomen with rebound tenderness in the right iliac fossa. Bowel sounds were absent.

Investigations

On admission, she underwent CT scanning (non-contrast, due to acute kidney injury), which was suggestive of colitis and which showed no signs of mesenteric ischaemia. While in the intensive care unit (ICU), microbiology was reported as positive for C. coli (sequence type 2273) and negative for Clostridium difficile. She was treated with intravenous antibiotics (amoxicillin, metronidazole and gentamicin with the addition of clarithromycin once campylobacter was identified as the source), and when she failed to improve by day 3 of her admission, with worsening abdominal pain, her lactate rose to 4.3 mmol/L. She underwent a second CT scan, this time with contrast. This showed some increased small bowel wall thickening, but no progression, and indeed some improvement, in the degree of colonic dilation. On day 9 of her admission, she underwent a third CT scan as her condition was not progressing. Again, this CT showed no change in colonic dilation and no new abdominal/pelvic finding. On the evening of day 9, the patient had rectal bleeding and a colonoscopy was planned for the following day. On day 10, colonoscopy was carried out in the ICU, which revealed extensive and severe deep ulceration with fissuring, from sigmoid to splenic flexure. This was suggestive of fulminant colitis rather than ischaemic colitis, as it extended beyond the hepatic flexure. Concerns over possible iatrogenic perforation, given the fragile mucosa, meant that colonoscopy was limited and not performed to the ileocaecal valve. Following total colectomy, the pathology report showed severe active fulminant colitis. There were no specific diagnostic features of inflammatory bowel disease (IBD) and the histological changes were reported to be consistent with the complications of severe gastro-intestinal infection. The patient also underwent an echocardiogram (echo) to rule out Campylobacter-associated myocarditis, as she had had a prolonged inotrope requirement. The echo showed a normal sized left ventricle, with normal left ventricular wall thickness, and preserved left ventricular systolic function. The right ventricle and atria were seen to be normal, and no abnormalities in the valves were detected. This report refuted the diagnosis of myocarditis. The ECG was also normal.

Differential diagnosis

At the time of admission, given the patient’s history and her husband’s recent diarrhoea and vomiting, infective colitis was thought the most likely diagnosis. However, IBD was also part of the working differential diagnosis and could not initially be excluded. Ischaemic colitis was thought less likely early in this patient journey, due to the absence of rectal bleeding, and the reassurance of the CT scan.

Treatment

On admission to hospital, she was treated with the following intravenous antibiotics empirically; amoxicillin, metronidazole and gentamicin, and clarithromycin was added once Campylobacter was isolated. After colonoscopy, the patient underwent total colectomy and splenectomy (for iatrogenic splenic trauma). Her preoperative National Emergency Laparotomy Audit score was 15.5% for mortality and 70.8% for morbidity. She returned to the ICU where she progressed over 50 days. During her ICU stay, she had a variable need for haemodynamic support and was weaned totally from this 28 days postoperatively. She was ventilated postoperatively and progressively weaned to a tracheostomy, and then a Mini-Trach. She required renal replacement with continuous veno-venous hemodialysis to manage acidosis and maintain fluid balance. She was supported nutritionally with enteral nutrition and total parenteral nutrition. She had several episodes of gastro-intestinal haemorrhage requiring transfusion with blood, blood products and tranexamic acid. She underwent two oesophago-gastro-duodenoscopies and one colonoscopy. Gastric ulceration was noted and the largest area required injection with sclerosant. Following this, she had no further episodes of haemorrhage. In addition to medical and surgical treatment, she required extensive physiotherapy for a polyneuropathy associated with critical illness.

Outcome and follow-up

The patient was transferred to a community hospital after a 93-day stay in secondary care. Fifty of these days were spent in ICU. She spent further 30 days as an inpatient in a community hospital for rehabilitation. She progressed well with physiotherapy and occupational therapy and was discharged home. She was seen in the outpatient clinic 1 month after discharge from the community hospital, and reported that she was doing well at home. A follow-up appointment was made for 4 months’ time, when discussion regarding reversal of ileostomy is planned to begin.

Discussion

Despite increasing awareness of the importance of food hygiene, driven by public health bodies, the incidence of campylobacter infection remains greater presently than 10 years ago, and it continues to be a major public health problem.¹ C. jejuni is the species most commonly isolated from faecal samples. However, 15 additional species have been isolated from humans and our patient was infected with the much less common pathogen C. coli.⁸ Treatment for campylobacter infection is most commonly supportive with replacement of electrolytes and prevention of dehydration. Where antibiotic treatment is indicated, for example in immunosuppressed patients, the elderly, and paediatric populations, the macrolide and fluoroquinolone classes of antibiotic are typically administered, although antibiotic resistance to these two classes is becoming increasingly problematic.⁹ Our patient received supportive treatment in the form of fluid and electrolyte replacement in addition to intravenous antibiotic therapy, from the outset of her admission, because of the severity of her illness at presentation. Initial management of this patient was led by the intensive care team and gastroenterologists. However, when she failed to improve to optimal medical therapy, colonoscopy revealed the severity of her colitis, and she immediately underwent total colectomy under the surgical team. Much of the current literature and evidenced-based treatment guidelines concern the management of severe enterocolitis, namely toxic megacolon, in the context of IBD (Crohns’ disease and ulcerative colitis) and C. difficile. In these examples, progressive colonic dilation, perforation, end organ failure and haemodynamic instability are all indications that urgent surgical intervention is warranted.^{10 11} Clinical assessment of our deteriorating patient was made more challenging by the fact that she was exhausted following an extensive period of sepsis; her communication of pain prior to surgery varied over the course of her admission and was often not consistent with clinical improvements or deteriorations. Despite the presence of microperforations on colonoscopy and a per rectal (PR) bleed suggestive of vascular involvement, she did not demonstrate clinical signs of peritonitis immediately prior to surgery on examination. Additionally, repeated CT scans completed shortly prior to surgery were falsely reassuring. Rising lactate, however, was indicative of poor end organ perfusion and declining oxygen delivery to bowel and likely other end organs. Our patient underwent total colectomy and formation of an ileostomy, according to current recommendation for management of toxic megacolon,⁵ and the septic focus of her illness was removed.

In many of the previously published case reports of campylobacter causing toxic megacolon, presentation at hospital was preceded by a much longer period of diarrhoeal illness at home, at least 10 days. Patients were generally young, and previously fit and healthy, and only one patient had significant comorbidities associated with hepatitis C and Child-Pugh B liver cirrhosis.⁶ All patients who required colectomy, with the exception of the aforementioned case who subsequently died, recovered without complication postoperatively. However, the clinical course of our patient was much more complex, and arguably she was most unwell in the weeks immediately postoperatively.

Finally, regarding the specific microbiology in this case, we know that the campylobacter isolated from our patient was not simply an incidental finding or case of colonisation but rather acute infection because her husband was also unwell and the same strain of C. coli (sequence type 2273) was also isolated from him. Reliability of the identification and typing of this organism was also assured as it was performed by whole genome sequencing; this, in conjunction with the histology, also supports the idea of acute infection rather than this being a case of campylobacter associated IBD in which Campylobacter concisus has been indicated.¹² Following discussion with the reference lab at the National Infection Service, we also know that this strain of campylobacter has not previously been identified as being especially pathogenic, is not frequently isolated from infection in the human population and that it is most commonly associated with food containing chicken.

Learning points.

• Although campylobacter typically causes a brief and self-limiting diarrhoeal illness, this pathogen can be associated with significant morbidity; in rare cases causing significant multiorgan failure and even death. Toxic megacolon can be caused by infective or inflammatory enterocolitis and should be a key differential diagnosis in a patient not responding to medical therapy for treatment of colitis.

• A multidisciplinary approach, with early involvement of a surgical team, and escalation to an appropriate level of care are essential in order to limit morbidity and improve outcomes in this rare patient cohort.

• Clinical examination and CT scans were falsely reassuring in this case, which perhaps suggests that in cases where medical management has failed, an emergency total colectomy and end ileostomy should be performed.