In light of the recently published IDSA guidelines on C. difficile, I thought I would write up a summary of the guidelines as well as provide some of the background microbiology of the organism for review.

Structure

• obligate anaerobes
• gram-positive bacilli
  – form spores (= dormant, non-reproductive structure that the bacteria can reduce itself to in order to survive for extended periods of time in extreme conditions)
• produce toxins (toxin A and toxin B) that cause disease

 

Environment

• animal and human feces
• soil
• sewage

 

Mechanism of pathogenicity

*Not all strains of C. difficile are pathogenic – only the ones who produce toxins can cause C. difficile disease

Pathogenesis:

Transmission occurs with ingestion of spores via the fecal-oral route ⇒ spores activate in the colon to replicating bacteria ⇒ bacteria release toxins ⇒ toxins cause breakdown of the colon cells’ cytoskeleton framework ⇒ apoptosis ⇒ breakdown of the mucosal wall ⇒ DIARRHEA!

 

Risk factors for acquiring C. difficile:

1. ANTIBIOTIC EXPOSURE
2. Exposure to healthcare facilities
3. Age and immunosuppression
4. ?Gastric acid suppression (use of proton pump inhibitors or H₂ receptor blockers)
   — the evidence-based-medicine jury is still out on this one

 

Clinical features

• symptoms can develop during antibiotic treatment or up to 6 weeks after the course of antibiotics has been finished
• patients can also become infected even without exposure to antibiotics (both in the healthcare setting but also in the community setting)
• carrier state = a patient who is colonized with C. difficile but is currently asymptomatic

1.Symptoms and physical exam signs:

• Non-bloody, WATERY DIARRHEA (≥ 3 loose stools in 24 hours)
  *occasionally patients can develop ileus with severe infection which will not result in diarrhea but rather lack of bowel movements
• Abdominal pain/cramping
• Fever and chills
• Abdominal distention/tenderness
• Nausea/anorexia

2.Laboratory findings:

• High white blood count (occasionally precedes the diarrhea by 1-2 days)
• Elevated creatinine
• Elevated lactate and low albumin (in fulminant cases)

 

Pseudomembranous colitis = inflammation of the colon causing elevated white and yellow-colored plaques to form and coalesce together to create a pseudomembrane on the colon wall that can be seen by colonoscopy.

 

Diagnostics

1. When to test: when patient has new onset, ≥ 3 unformed stools that cannot be explained by another cause (i.e. laxative use)
2. Options for testing:

* C. difficile can be grown in culture, but anaerobes take a while to grow and it would not provide an answer as to whether the strain is toxigenic (i.e. produces toxin) or not, so it is not commonly used for clinical diagnostic purposes.

	What it is	Advantages	Disadvantages
Toxin EIA assay	Antibody assay that detect toxins	High specificity (>84%)	Low sensitivity (31-99%)
GDH assay	Detects GDH (an enzyme produced by C. difficile)	High NPV (>99%) Quick turn-around	Cannot distinguish toxigenic vs. non-toxigenic C. difficile strains
NAAT/PCR	PCR method that detects toxin production gene	High NPV (>99%) Quick turn-around	Poor specificity and PPV *Changes depending on whom specimens are collected on (low suspicion vs. high suspicion)

EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NPV, negative predictive value; PPV, positive predictive value; NAAT, nucleic acid amplification test; PCR, polymerase chain reaction.

Many healthcare facilities are currently doing only PCR testing. It’s highly sensitive and the results return quickly (usually within 24 hours).

The problem: this practice is yielding a lot of false positives (patients who are carriers but do not truly have an active infection) which ⇒ over-treatment ⇒ patient discomfort, potential side effects, infection control consequences for the hospital, and extra costs.

Why: This is thought to be due to the fact that a lot of tests are sent inappropriately (on patients that have diarrhea but no other evidence of infection such as leukocytosis, AKI, abdominal pain, fever, etc.)

Solution (as proposed by IDSA guidelines):

1. A multiple step algorithm:

• GDH assay + EIA assay
• GDH assay + EIA assay with NAAT as a tiebreaker
• NAAT + EIA assay

                  OR

2. We can agree to be more mindful of when we send the test (when the pre-test probability is high) and continue to use the NAAT/PCR method alone.

Bottom line: Many hospitals are switching over to the two-step testing method for multiple reasons:

• behavior change is difficult to implement and sustain
• provides more accurate incidence of nosocomial-acquired infections in the hospital

WHEN YOU THINK OF SENDING A C. DIFFICILE TEST, ask yourself:

1. Does this patient have an unexplained fever, leukocytosis, or new abdominal pain/distention, in addition to the diarrhea (or in presence of ileus)?
   – if yes ⇒ send the test

2. If not, is there another explanation for the diarrhea?
   (i.e. laxatives, new medications (especially antibiotics), part of already known illness, etc.)
   – if yes ⇒ consider removing the potential cause (if possible) and re-evaluate or monitor for worsening symptoms
   – if not ⇒ send the test

 

Treatment

The IDSA has a really great table to reference when choosing treatment options for your C. difficile infected patient.

***PO Metronidazole is no longer the 1^st-line agent for C. diff infection treatment***

                                                                                                            McDonald et al. CID 2018

 

Recurrence

Recurrence of C. difficile infection = reappearance of symptoms within 2-8 weeks after completion of therapy

• up to 25% of patients will experience a recurrence
• once patient had one recurrence, they are at higher risk for future recurrences

 

TAKE-HOME POINTS:

• The MAJOR risk factor for C. difficile infection is ANTIBIOTIC EXPOSURE
  ⇒ DO NOT give antibiotics to those who do not truly need them
• Symptoms/signs include watery diarrhea, abdominal cramping/pain, and elevated WBC and creatinine
• C. difficile infection CAN cause ileus (i.e. no diarrhea)
• Only send test when you have a high pre-test probability to avoid false positives
• Metronidazole is NO LONGER recommended for treatment of C. difficile

 

Got questions? Disagree? Leave your comments below!

 

References

1. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018. 66(7):1-48. [PMID: 29562266]
2. Jorgensen JH, Pfaller MA, Carroll KC, et al. Manual of Clinical Microbiology, Eleventh Edition.
3. Lamont JT. (2018). Clostridium difficile infection in adults: Epidemiology, microbiology, and pathophysiology. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/clostridium-difficile-infection-in-adults-epidemiology-microbiology-and-pathophysiology]. Accessed May 25, 2018.
4. Lamont JT, Kelly CP, and Bakken JS. Clostridium difficile infection in adults: Clinical manifestations and diagnosis. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/clostridium-difficile-infection-in-adults-clinical-manifestations-and-diagnosis]. Accessed May 25, 2018.
5. Kelly CP, Lamont JT, and Bakken JS. Clostridium difficile infection in adults: Treatment and prevention. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/clostridium-difficile-infection-in-adults-treatment-and-prevention]. Accessed May 25, 2018.