Clostridium Difficile Infection and Surgical Treatment

Clostridium Difficile Infection

Clostridium difficile infection (CDI) manifests symptoms ranging from asymptomatic carrier state to fulminant colitis. CDI is the most common cause of healthcare-associated diarrhea.

The prevalence of asymptomatic colonization among hospitalized patients ranges from 3% to 26%. Clostridium difficile is an anaerobic, spore-forming, gram-positive bacillus.

Transmission Routes of Clostridium Difficile Infection

1. Person to Person: Transmission occurs through the feco-oral route.
2. Contaminated Environment: Exposure to contaminated environments leads to ingestion of spores.
3. Healthcare Personnel: Transmission via healthcare personnel hands necessitates hand hygiene to reduce the risk of hospital-acquired infections.

Toxins Produced by Clostridium difficile

Clostridium difficile produces two toxins: Toxin A and Toxin B.

The Mechanism of Action of these toxins binds to colonic epithelial cell glycoproteins, causing colonocyte death and the release of inflammatory mediators.

A Special Strain is Ribotype 027. Ribotype 027 strain of Clostridium difficile emerged in the mid-2000s, resulting in severe disease outcomes and death across Western countries. Patients infected with this strain have severe disease outcomes and an increased risk of death.

Risk Factors for Clinical Infection

The Primary Risk Factor is Recent exposure to antibiotics. The Antibiotics Associated with Higher Risk are:

• 3rd to 4th generation cephalosporins
• Fluoroquinolones
• Clindamycin
• Carbapenems

The Other Risk Factors for Clostridium Difficile Infection

1. Immunodeficiency: Especially in patients with HIV, undergoing chemotherapy, or experiencing neutropenia post-chemotherapy.
2. Use of Acid Suppressing Medications: Prolonged use of proton pump inhibitors (PPIs) increases the risk.
3. Gastrointestinal Surgery: Manipulation of the GI tract, particularly during tube feeding, increases the risk.
4. Prolonged Hospitalization: Patients with lengthy stays in hospitals or nursing homes are at higher risk.
5. Inflammatory Bowel Disease (IBD): Patients with IBD, due to antibiotic and steroid use, have increased rates of colectomy and worse outcomes.

Factors Increasing Risk of Death in Clostridium difficile Infection

These factors help in increasing the risk of death during Clostridium difficile infection.

• Elderly Patients with Comorbidities: Advanced age and multiple comorbidities increase the risk of death.
• Hypoalbuminemia: Low albumin levels are associated with increased mortality.
• Acute Renal Failure: Patients with acute renal failure have a higher risk of death.
• Special Strain Ribo Type 027: Infection with this strain exacerbates the risk of death.

Symptoms of Clostridium difficile Infection

The Symptoms of Clostridium difficile infection typically appear 4 to 9 days after initiating antibiotic treatment. The Patients usually present with new-onset unexplained watery diarrhea, often passing 3 or more unformed stools in 24 hours. Abdominal pain, fever, and leukocytosis are common manifestations of Clostridium difficile infection.

Classification of Clostridium difficile Infection

1. Asymptomatic Colonization: Some patients may carry the bacterium without symptoms.
2. Non-severe Disease: Patients exhibit symptoms but without severe complications.
3. Severe Disease: Characterized by predictors such as leukocytosis and elevated serum creatinine.
4. Fulminant Disease: Severe complications like hypotension, ileus, or megacolon indicate fulminant infection.

Predictors of Severe Disease

The Infectious Disease Society of America has developed predictors of severe disease in clostridium difficile infection.

• Leukocytosis: Leukocyte count should be at least 15,000 per microliter.
• Serum Creatinine: Levels should be at least 1.5 milligrams per deciliter.

Fulminant Clostridium difficile Infection

Clinical features like Hypotension, shock, ileus, or megacolon suggest severe or fulminant infection. Fulminant or severe infection is diagnosed based on clinical indicators at presentation.

Diagnosis of Clostridium difficile Infection 

The Diagnosis relies on typical symptoms coupled with stool testing. The following Tests aim to detect Clostridium Difficile toxins, antigens, or bacteria.

Tests:

1. ELISA: For toxin detection.
2. Glutamate Dehydrogenase (GDH) Immunoassays: Detect Clostridium Difficile antigen.
3. Nucleic Acid Amplification Test (NAAT).
4. PCR and Stool Culture.

Role of Flexible Sigmoidoscopy

Not First-line Modality: Flexible sigmoidoscopy is not the primary diagnostic tool.

• Flexible sigmoidoscopy can provide additional diagnostic clarity when stool testing results are inconclusive.
• It helps in ruling out alternative causes of symptoms.

Appearance:

• Pseudomembranes: Flexible sigmoidoscopy reveals raised yellow-white plaques, known as pseudomembranes.
• Size: These plaques typically measure 2 to 10 mm.
• Frequency: Pseudomembranes are observed in approximately half of the patients undergoing examination.

Histological Findings from Pseudomembrane Biopsies

• Histological examination reveals the presence of inflammatory exudate.
• Mucinous Debris
• Cellular Components: Biopsies show fibrin, necrotic epithelial cells, and polymorphonuclear cells (neutrophils).

Role of Colonoscopy in Fulminant Colitis

Colonoscopy increases the risk of perforation, especially in patients with fulminant colitis. Therefore, it should be performed only when the potential benefits outweigh the risks of complications.

Imaging Findings 

Following are the CT Scan Findings:

1. Colonic Wall Thickening
2. Bowel Dilatation
3. Pericolonic Fat Stranding
4. Accordion Sign: Alternating high and low attenuation of oral contrast resembling an accordion, typically seen in pseudomembranous colitis.

Following are the Ultrasound Findings:

1. Bowel Wall Thickening
2. Luminal Narrowing
3. Pseudomembranes: Hyper echoic lines covering the mucosa.

Atlas Criteria for Assessing Response to Treatment

Atlas Criteria is used as a clinical bedside score to evaluate the response to treatment.

• A: Age
• T: Temperature
• L: Leukocytosis
• A: Albumin levels
• S: Systemic antibiotic treatment

Initial Treatment for Clostridium Difficile Infection

1. Discontinue Previous Antibiotics: Stop or minimize the antibiotic that triggered the infection.
2. Intravenous Fluids: Administer IV fluids to maintain hydration and correct electrolyte imbalances.
3. Avoidance of Anti-peristaltic Agents: Anti-peristaltic agents should be avoided in the treatment of Clostridium Difficile infection.

Antibiotic Treatment

The following treatment is administered for the First Episode of Clostridium difficile infection.

• Oral Vancomycin 125mg four times daily.
• Fidaxomicin 200mg twice daily.
• Metronidazole 500mg three times daily (for non-severe cases).

The following treatment is administered for the First Episode of Clostridium difficile Fulminant Disease:

• Vancomycin: Oral or via nasogastric tube: 500mg four times daily.
• For patients with ileus: Rectal installation of vancomycin.
• IV Metronidazole: 500mg every 8 hours, along with oral or rectal vancomycin.

The treatment duration is 10 days for a non-severe disease, and in the case of a Fulminant Disease, treatment is done for at least 10 days, with an individualized treatment duration.

The Initial Steps are to Discontinue triggering antibiotics and provide IV fluids. Anti-peristaltic Agents should be avoided; they should not be used in Clostridium Difficile infection treatment.

Antibiotic Choices that can be used are Oral vancomycin or fidaxomicin, which are preferred for first episodes, with metronidazole as an alternative. In cases of fulminant disease, vancomycin or IV metronidazole with oral or rectal vancomycin can be used. As discussed earlier, Treatment duration varies based on disease severity, with individualized approaches recommended.

Fecal Microbiota Transplant 

Fecal Microbiota Transplant (FMT)

• Purpose: FMT is a relatively new treatment, especially for patients experiencing recurrent episodes of Clostridium difficile infection (CDI).
• Mechanism: Patients with CDI lack protective colonic microbiota, making them susceptible to colonization by Clostridium difficile. FMT involves reimplanting normal gut bacteria from healthy donors to restore gut biodiversity and correct microbial imbalance.

Role of Surgery in Clostridium Difficle Infection

Following are the Indications for Surgery

• Fulminant Clostridium difficile infection.
• Development of signs of systemic toxicity.
• Toxic megacolon or perforation.

Following are the Indications of Emergency Surgery

• In patients with fulminant colitis and signs of systemic toxicity or perforation, emergency surgery is warranted.
• Emergency colectomy provides a survival advantage compared to antibiotic treatment.

Surgical Treatment Options

In the case of Severely Ill Patients, Total or Subtotal Colectomy is preferred. The preservation of the rectum is attempted whenever feasible during this surgery.

In Patients without Necrosis or Perforation, a Diverting Loop Ileostomy is considered. During surgery, an on-table colonic lavage is performed. Post-lavage, antegrade vancomycin flushes are administered to the colon.

Frequently Asked Questions:

Q: What is the Primary Risk Factor of Clostridium Difficile Infection?

Answer: Recent exposure to antibiotics

Q: What surgery is performed in Patients without Necrosis or Perforation Clostridium with Difficile Infection?

Answer: Diverting Loop Ileostomy

Question: What is the dosage and route of Vancomycin for clostridium difficile infection?

Answer: Vancomycin is given Orally or via a nasogastric tube in the dose of 500mg four times daily.

Hope you found this blog helpful for your GIT, Hepatobiliary and Pancreatic Surgery preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.