Treatment of Antibiotic-Associated Diarrhea
The first and most critical step is to discontinue the causative antibiotic immediately when clinically feasible, as this alone resolves most mild cases and significantly reduces recurrence risk. 1, 2
Initial Management Approach
Discontinue the offending antibiotic as soon as possible, since continued use decreases clinical response rates and increases recurrence of diarrhea 1, 2. If ongoing antimicrobial therapy is absolutely necessary for another infection, switch to agents less commonly associated with C. difficile infection such as parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline 1.
Initiate rehydration therapy immediately based on severity 2:
- For mild to moderate dehydration: Use reduced osmolarity oral rehydration solution (ORS) as first-line therapy 1, 2
- For severe dehydration, shock, altered mental status, or ileus: Administer isotonic intravenous fluids (lactated Ringer's or normal saline) until clinical stabilization occurs 1, 2
Implement dietary modifications including elimination of lactose-containing products, alcohol, and high-osmolar dietary supplements 2.
Management Based on Severity and Etiology
For Mild, Non-C. difficile Antibiotic-Associated Diarrhea
Symptomatic management with loperamide is appropriate for immunocompetent adults: initial dose of 4 mg followed by 2 mg every 4 hours or after each unformed stool 2. However, avoid antimotility agents entirely in children under 18 years, patients with bloody diarrhea, or those with fever due to risk of complications including toxic megacolon 2.
Consider probiotic preparations to reduce symptom severity and duration in immunocompetent patients, though evidence remains limited 2.
For Confirmed Clostridioides difficile Infection (CDI)
Vancomycin 125 mg orally four times daily for 10 days or fidaxomicin 200 mg orally twice daily for 10 days are the preferred first-line treatments for initial CDI episodes 1, 3. This represents a strong recommendation based on high-quality evidence showing superiority over metronidazole 1.
Fidaxomicin is FDA-approved for CDI in adults and pediatric patients 6 months and older, with weight-based dosing available for children 3. The drug can be administered with or without food 3.
Metronidazole 500 mg orally three times daily for 10 days may be used only in settings where access to vancomycin or fidaxomicin is limited, and only for initial episodes of non-severe CDI 1. Avoid repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity 1.
For Severe or Complicated CDI
Vancomycin remains the treatment of choice for severe CDI, with clinical cure rates of 97% compared to 76% for metronidazole in severe disease 1. For fulminant CDI (defined as hypotension/shock, ileus, or megacolon), higher doses of oral vancomycin up to 500 mg four times daily have been used, though evidence is limited 1.
Start empiric antibiotic therapy for CDI if substantial delay in laboratory confirmation is expected (>48 hours) or if fulminant CDI is suspected 1.
For Recurrent CDI
Fecal microbiota transplantation (FMT) is highly effective for patients with multiple CDI recurrences who have failed appropriate antibiotic treatments 1. The rationale is restoration of normal colonic flora balance that prevents C. difficile overgrowth 1.
Bezlotoxumab (a monoclonal antibody against C. difficile toxin B) may be used as adjunctive therapy to prevent recurrences, particularly in high-risk patients including those with the 027 epidemic strain, immunocompromised patients, and those with severe CDI 1.
Critical Infection Control Measures
Hand hygiene with soap and water is mandatory when caring for patients with suspected or confirmed CDI, as alcohol-based hand sanitizers do not kill C. difficile spores or effectively remove them from hands 1, 2.
Implement contact precautions with gloves and gowns for all healthcare workers 1, 2. Place patients in private rooms with dedicated bathroom facilities when possible, or use cohort nursing for confirmed CDI patients 1, 2.
Discontinue unnecessary proton pump inhibitors (PPIs), as there is a clinical association between PPI use and increased CDI risk, though the evidence for discontinuation improving outcomes requires further study 1, 2.
Important Pitfalls to Avoid
Never use antimotility agents in children under 18 years or in patients with bloody diarrhea, fever, or suspected invasive pathogens 2. This can precipitate toxic megacolon and other serious complications 2.
Avoid antibiotics for STEC O157 infections (Shiga toxin-producing E. coli), as they increase the risk of hemolytic uremic syndrome 1, 2.
Do not routinely use probiotics for primary prevention of CDI in hospitalized patients, as meta-analyses show significant limitations and potential bias in studies, plus risk of probiotic-related infections in hospitalized patients 1.
Empiric antimicrobial therapy is not recommended for most cases of acute watery diarrhea without recent international travel, except in immunocompromised patients or ill-appearing young infants 1.