Introduction

Pseudomembranous colitis is a severe condition of the colon (large intestine), most commonly caused by Clostridium difficile infection (C. difficile), though it can result from various other factors.¹ Before the widespread use of broad-spectrum antibiotics, it was more frequently linked to conditions like ischemic disease, obstruction, and sepsis. However, with the advent of newer antibiotics, C. difficile has become the predominant cause, while the condition can now be associated with nearly all types of antibiotics.² Despite available treatments for C. difficile-related pseudomembranous colitis, the condition remains a significant clinical concern due to its persistence, potential complications, and its close association with the repeated use of broad-spectrum antibiotics.

This article will explore the multifaceted nature of pseudomembranous colitis, including its causes, risk factors, diagnostic methods, treatment options, preventive strategies, and other relevant aspects.

Causes and risk factors

Clostridium difficile (C. difficile) is the most common cause of pseudomembranous colitis. However, other less frequent causes include:³ 

• Ischemic colitis
• Collagenous colitis
• Inflammatory bowel disease (IBD)
• cytomegalovirus-induced colitis
• Vasculitis
• Bacterial and parasitic infections
• Behcet’s disease
• Chemotherapy
• Toxins, like heavy metal poisoning

While C. difficile is often associated with hospital-acquired infections, it primarily affects elderly individuals who have a history of antibiotic use or hospital stays.³ Additional risk factors for C. difficile infection include:³ 

• Previous C. difficile infection
• Advanced age
• Use of gastric acid-suppressing medications
• Gastrointestinal surgery
• Feeding tubes
• Immunodeficiency
• Chemotherapy
• Chronic kidney disease
• Inflammatory bowel disease (IBD) 

However, it’s important to note that the absence of these risk factors does not rule out a C. difficile infection.³

Impact of C. difficile on normal body functioning

The use of antibiotics, chemotherapeutic drugs, or immunosuppressive therapy disrupts the normal colonic microbiome, creating an environment that allows C. difficile colonisation. C. difficile causes colitis by producing toxins A and B, which trigger inflammation, disrupt the colonic cell cytoskeleton, and lead to cellular death. Pseudomembranes in pseudomembranous colitis form as these toxins overstimulate the immune system, attracting neutrophils to attack the colonic mucosa.³

Clinical presentation and symptoms

Patients with pseudomembranous colitis usually report symptomatic diarrhoea. Some patients might not show any signs of illness, while others could experience fulminant or explosive pseudomembranous colitis leading to toxic megacolon. Generally, the presence of pseudomembranes points to a more severe case of C. difficile infection or antibiotic-associated diarrhoea. Other remarkable symptoms and signs include fever, abdominal cramping, and elevated white blood cell (WBC) count.³

Severe pseudomembranous colitis can result in a significant increase in white blood cell counts, reaching up to 100,000/mm³, along with hypovolemia, hypotension, protein-losing enteropathy, reactive arthritis, and toxic megacolon. Approximately 3% to 8% of cases progress to fulminant infection, which may involve severe ileus, toxic megacolon, hypovolemia, hypotension, renal dysfunction, colonic perforation with attendant peritonitis, and septic shock.³

Diagnosis

The diagnosis of pseudomembranous colitis typically involves a multi-level approach: clinical evaluation, stool tests for enteric microorganisms, and visualisation of the colonic mucosa.²

The process begins with a thorough medical history and clinical presentation. A history of recent antibiotic use, hospitalisation, intestinal surgery, or residence in a long-term care facility can suggest pseudomembranous colitis. Common symptoms include watery diarrhoea, abdominal pain or cramping, and fever.² Next, stool tests are conducted to detect C. difficile, which is a key diagnostic marker for the condition. These tests are routinely performed.² Finally, colonoscopy or sigmoidoscopy may be used to visually confirm the presence of pseudomembranes, particularly when an immediate diagnosis is crucial.²

Treatment

Although only oral vancomycin and fidaxomicin have been approved by the US Food and Drug Administration ‘(FDA) for the treatment of C. difficile colitis, metronidazole was used as a first-line treatment for four decades. Studies have shown that metronidazole and vancomycin are nearly equally effective for mild to moderate C. difficile colitis as initial therapies.³ However, for more severe cases, treatment must be adjusted. Criteria for severe C. difficile colitis include:³

• Leukemoid reaction greater than 35,000/mm³
• Hypotension
• ICU admission
• Elevated serum lactate
• End-organ damage (e.g., acute kidney injury or delirium)

For these severe cases, oral vancomycin is preferred due to its superior cure rates.

In cases of fulminant C. difficile pseudomembranous colitis, where the disease is unresponsive to medication or complications such as toxic megacolon or colonic perforation arise, surgical intervention (e.g., hemicolectomy) may be necessary.³

Recurrent C. difficile colitis is common after initial treatment. The usual approach is to reinstitute the original antibiotic therapy unless the disease worsens. In cases of three or more recurrences despite treatment with oral vancomycin, faecal microbiota transplantation has shown promise in small studies.³

Evidence-based outcomes

Individuals experiencing mild C. difficile colitis typically recuperate and exhibit a positive outlook for recovery. Many of them will only require supportive therapy such as hydration. However, those with severe colitis can develop dehydration, electrolyte deficiencies, and persistent diarrhoea that can last several weeks. In these patients, treatment is recommended.³

Most individuals begin to show improvement within seven to ten days of starting treatment with metronidazole or vancomycin. However, around 20% of patients may experience a decline after completing their treatment, and these individuals are more likely to experience recurrent episodes.³

Prevention of C. difficile infection

Preventing C. difficile infection is challenging and requires strict adherence to established guidelines, particularly for vulnerable patients. Preventive measures in hospitals include:⁴

• Judicious use of antibiotics
• Hand hygiene between patient contacts
• Rapid laboratory detection of C. difficile
• Isolation of patients with C. difficile-associated diarrhoea
• Precautionary measures during interactions with patients and their environment
• Thorough disinfection of objects with appropriate agents
• Staff education
• Continued precautions until diarrhoea subsides

Antibiotic stewardship programs, which focus on limiting high-risk antibiotics and minimising unnecessary use, have been shown to be effective in both outbreak and non-outbreak settings, helping to control C. difficile infection rates.⁵

The role of probiotics in preventing C. difficile infection remains debated. While Lactobacilli have been shown to reduce antibiotic-associated diarrhoea, they have not been proven to prevent C. difficile-associated diarrhoea.⁴ There is limited high-quality evidence to support the widespread use of probiotics for most conditions.⁵ Additionally, recommended formulations are often costly (ranging from $30 to $100 monthly) and typically not covered by insurance. Consequently, the American College of Gastroenterology concludes that there is insufficient evidence to recommend probiotics for the primary or secondary prevention of C. difficile infection in most patients.⁵

Summary 

• Pseudomembranous colitis is a serious inflammatory condition of the colon, most commonly caused by Clostridium difficile (C. difficile), though other factors can also contribute
• Pseudomembranous colitis can be caused by C. difficile infection, as well as conditions like ischemic colitis, inflammatory bowel disease, and certain medications
• A thorough patient history, including symptom duration and medical background, is essential for diagnosis
• Treatment should be tailored to the underlying cause
• Infection control and antibiotic stewardship are effective in hospital settings, but community spread remains a growing concern