Clostridioides difficile Infection (CDI) Treatment Protocol
1.0 Purpose and Scope
This protocol establishes a standardized, evidence-based framework for the diagnosis and management of Clostridioides difficile infection (CDI). Its strategic importance lies in unifying our clinical approach to improve patient outcomes, reduce the incidence of recurrence, and ensure the appropriate stewardship of antimicrobial and biologic therapies. By adhering to this protocol, we aim to optimize care from the initial diagnosis through the management of complex, recurrent disease.
The scope of this document applies to the diagnosis, severity assessment, and staged treatment of initial and recurrent CDI in adult patients within our clinical and hospital settings. It provides clear therapeutic pathways based on disease severity and treatment history. Successful management begins with a precise and timely diagnosis, the criteria for which are detailed in the following section.
2.0 Diagnostic Criteria and Definitions
Accurate diagnosis is the cornerstone of effective CDI management. This principle prevents the inappropriate treatment of asymptomatic colonization, which can further disrupt the gut microbiome, while ensuring that timely and decisive intervention is initiated for true infection. This section defines the precise criteria required to diagnose an active infection and to classify a subsequent recurrence.
2.1 Defining Active CDI
A diagnosis of active CDI is a clinical diagnosis supported by laboratory evidence. It requires the presence of BOTH of the following criteria:
Clinical Symptoms: The patient must present with clinically significant diarrhea, defined as the passage of three or more unformed stools in a 24-hour period for which there is no other obvious cause (e.g., laxative use, new enteral feeding formula).
Laboratory Evidence: A stool sample must test positive for the presence of a toxin-producing strain of C. difficile.
Crucially, patients with formed stool or who are asymptomatic should not be tested for CDI. A positive laboratory test in an asymptomatic individual signifies colonization, not active infection, and does not warrant antimicrobial therapy.
2.2 Interpreting Laboratory Tests
This protocol is based on a standard two-step testing algorithm involving a nucleic acid amplification test (PCR) and a toxin enzyme immunoassay (EIA). The combination of these results dictates the clinical interpretation and subsequent action. When both PCR and toxin EIA are positive, this indicates active CDI requiring treatment. When PCR is positive but toxin EIA is negative, this suggests colonization rather than active infection, and treatment should be withheld unless clinical suspicion remains high. When both tests are negative, CDI is ruled out.
2.3 Defining Recurrence
A CDI recurrence is formally defined as the reappearance of clinical symptoms (≥3 unformed stools/24 hours) accompanied by a positive stool test within 8 weeks of completing therapy for a prior episode. This timeline suggests a relapse from persistent spores. An episode that occurs more than 8 weeks after the completion of therapy is typically considered a reinfection or a new episode.
Once an active infection is confirmed, the next critical step is to assess its severity, which directly guides the initial therapeutic choice.
3.0 Initial Patient Assessment and Severity Staging
The strategic staging of disease severity is a critical decision point in CDI management. This assessment determines not only the choice and dose of antimicrobial therapy but also dictates the need for a higher level of care, intensive monitoring, and immediate surgical consultation.
3.1 Non-Fulminant CDI
A case of CDI is classified as non-fulminant if it does not meet any of the criteria for fulminant disease listed below. This category encompasses the majority of initial CDI episodes.
3.2 Fulminant CDI
Fulminant CDI is a severe, life-threatening presentation characterized by systemic toxicity and colonic collapse. A diagnosis of fulminant CDI is made if any of the following are present:
The following sections will outline the specific treatment pathways based on this crucial severity assessment.
4.0 Management of an Initial CDI Episode
The primary goals for treating an initial episode of CDI are to achieve clinical resolution of symptoms and, critically, to minimize the risk of subsequent recurrence. The choice of therapy is guided by disease severity and patient-specific risk factors for relapse.
4.1 Treatment of Non-Fulminant Initial CDI
Preferred Therapy: Fidaxomicin
Alternative Therapy: Vancomycin
Not Recommended: Metronidazole is no longer recommended as a first-line agent for the treatment of an initial episode of CDI in adults due to inferior cure rates.
4.2 Treatment of Fulminant CDI
The management of fulminant CDI requires an aggressive, multi-modal antibiotic regimen to maximize drug delivery to all compartments of the compromised colon.
Fidaxomicin has no role in the management of fulminant CDI, as its efficacy depends on a functioning gastrointestinal tract for drug delivery, which is compromised in the setting of ileus.
4.3 Surgical Consultation for Fulminant CDI
A surgical consultation must be obtained immediately upon diagnosis of fulminant CDI. This is a co-management strategy initiated at diagnosis, not a rescue consult for when medical therapy fails. The following clinical triggers indicate an immediate need for surgical evaluation for colectomy:
4.4 Adjunctive Therapy to Reduce Recurrence Risk
For patients with an initial episode who are at high risk of recurrence, the addition of bezlotoxumab is recommende...
