Treatment of Antibiotic-Associated Diarrhea
The first step in managing antibiotic-associated diarrhea is to discontinue the offending antibiotic when clinically feasible, followed by oral rehydration therapy for all patients, with specific antimicrobial treatment reserved only for confirmed Clostridioides difficile infection using oral vancomycin (125 mg four times daily for 10 days) or fidaxomicin (200 mg twice daily for 10 days) as first-line agents. 1, 2
Initial Management Approach
Discontinue the causative antibiotic immediately if possible, as this alone resolves most mild cases of antibiotic-associated diarrhea without C. difficile involvement 1, 3. If continued antibiotic therapy is required for the primary infection, switch to agents less frequently associated with C. difficile infection, including parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline 2.
Rehydration Strategy
Oral rehydration solution (ORS) with reduced osmolarity is the first-line therapy for mild to moderate dehydration in all patients with antibiotic-associated diarrhea 2, 1. This recommendation carries strong evidence and should be implemented immediately 2.
For severe dehydration, shock, altered mental status, or ileus, administer isotonic intravenous fluids (lactated Ringer's or normal saline) until pulse, perfusion, and mental status normalize 2, 1. Continue IV rehydration until the patient awakens, has no aspiration risk, and shows no evidence of ileus 2.
Symptomatic Treatment for Non-C. difficile Diarrhea
For mild to moderate diarrhea in immunocompetent adults without fever or bloody stools, loperamide may be used at an initial dose of 4 mg followed by 2 mg every 4 hours or after each unformed stool 1, 2.
Critical caveat: Never use antimotility agents in children under 18 years of age or in patients with bloody diarrhea, fever, or suspected inflammatory diarrhea due to risk of complications including toxic megacolon 1, 2. This is a common and dangerous pitfall.
If diarrhea persists beyond 48 hours on loperamide, discontinue it and consider second-line agents such as subcutaneous octreotide (500 mcg three times daily) 2, 1.
Treatment of Confirmed C. difficile Infection
First-Line Therapy
Oral vancomycin 125 mg four times daily for 10 days is superior to metronidazole for severe C. difficile infection 2. Vancomycin is considered the preferred first-line agent based on current evidence 2.
Fidaxomicin 200 mg orally twice daily for 10 days is an equally effective alternative to vancomycin and may be particularly useful for patients at high risk for recurrence, including elderly patients with multiple comorbidities receiving concomitant antibiotics 2, 4.
Severity-Based Approach
For mild to moderate initial episodes, metronidazole may be considered as an alternative, though it has more gastrointestinal side effects than vancomycin 1, 5. However, the 2020 World Journal of Emergency Surgery guidelines emphasize that metronidazole should be limited to initial episodes of mild-moderate disease 2.
For severe or fulminant C. difficile infection (defined as hypotension, shock, ileus, or megacolon), higher doses of oral vancomycin up to 500 mg have been used, though evidence for this dosing is limited 2.
Recurrent Infection
Fecal microbiota transplantation (FMT) is the most effective option for patients with multiple C. difficile recurrences who have failed appropriate antibiotic treatments 2. FMT works by restoring normal colonic flora balance that was disrupted by antibiotics 2.
Bezlotoxumab, a monoclonal antibody against C. difficile toxin B, may prevent recurrences particularly in patients with the 027 epidemic strain, immunocompromised patients, and those with severe disease 2, 1.
Infection Control Measures
Hand hygiene with soap and water is mandatory when caring for patients with suspected or confirmed C. difficile infection, as alcohol-based hand sanitizers do not kill C. difficile spores or remove them from hands 2, 1. This is a critical infection control measure that is frequently overlooked.
Use contact precautions including gloves and gowns for all patient contact 2, 1. Place patients in private rooms with dedicated bathroom facilities when possible 2.
Discontinue unnecessary proton pump inhibitors, as they are associated with increased risk of C. difficile infection, though the evidence for discontinuation reducing risk requires further study 2, 1.
Dietary Modifications
Eliminate lactose-containing products, alcohol, and high-osmolar dietary supplements during the acute phase 1. Consider lactose intolerance only if clinical symptoms occur after ingestion of milk products 2.
Resume an age-appropriate usual diet immediately after rehydration is complete 2. Continue human milk feeding in infants throughout the diarrheal episode 2.
When NOT to Treat
Do not use empiric antimicrobial therapy for most patients with acute watery diarrhea without recent international travel 2. Exceptions include immunocompromised patients or ill-appearing young infants 2.
Never use antibiotics for STEC O157 infections or other STEC producing Shiga toxin 2, as they increase the risk of hemolytic uremic syndrome 2, 1.
Role of Probiotics
Probiotics (particularly Saccharomyces boulardii and Lactobacillus species) may reduce symptom severity and duration in immunocompetent patients 1, 3. However, safety data in immunocompromised patients are lacking, so probiotics should be used cautiously in neutropenic or severely immunosuppressed patients 2.