When to use and avoid empirical antibiotics in patients with diarrhea, particularly those with a history of inflammatory bowel disease, immunocompromised status, or previous Clostridioides (C. difficile) infection?

When to Avoid Empirical Antibiotics in Patients with Diarrhea

Empirical antibiotics should be avoided in most patients with acute watery diarrhea, in all cases of suspected or confirmed STEC infection, and in patients with persistent watery diarrhea lasting ≥14 days. 1

Absolute Contraindications to Empirical Antibiotics

STEC Infections (Shiga Toxin-Producing E. coli)

• Never administer antibiotics to patients with STEC O157:H7 or any STEC producing Shiga toxin 2, as this significantly increases the risk of hemolytic uremic syndrome (HUS) and mortality 1, 2
• This prohibition applies to fluoroquinolones, β-lactams, trimethoprim-sulfamethoxazole, metronidazole, and azithromycin 1
• Even when the toxin genotype is unknown in STEC infections, antibiotics should be avoided 1
• The evidence supporting this recommendation is of moderate quality and represents a strong consensus 1

Acute Watery Diarrhea Without High-Risk Features

• Empirical antibiotics are not recommended for immunocompetent patients with acute watery diarrhea who lack recent international travel 1, 2
• The rationale: most cases are viral and self-limited, with antibiotics providing only modest benefit (average 1 day reduction in symptoms) while risking antimicrobial resistance and C. difficile infection 1, 3
• This is a strong recommendation despite low-quality evidence 1

Persistent Watery Diarrhea (≥14 Days)

• Empirical treatment should be avoided in patients with persistent watery diarrhea lasting 14 days or more 1
• At this stage, specific diagnostic testing is required to identify the causative pathogen or non-infectious etiology 1, 4

Clinical Scenarios Requiring Caution

Asymptomatic Contacts

• Never treat asymptomatic contacts of patients with bloody or watery diarrhea empirically 1, 2
• Instead, advise appropriate infection prevention and control measures 1
• This is a strong recommendation with moderate-quality evidence 1

Salmonella Gastroenteritis (Non-Typhoidal)

• Antibiotics are generally not recommended for uncomplicated Salmonella diarrhea in immunocompetent patients 1
• Antimicrobial treatment increases prolonged fecal shedding and may promote quinolone-resistant strains 1
• Exception: severely immunocompromised patients or those with signs of invasive disease may warrant treatment 1

Campylobacter Infections

• While antibiotics reduce illness duration by approximately 1 day, the benefit is modest and greatest when treatment begins early 1
• The treatment effect is small enough that empirical therapy is not routinely recommended without confirmed diagnosis 1
• Quinolone resistance can develop during therapy 1

Special Populations Requiring Individualized Assessment

Inflammatory Bowel Disease (IBD) Patients

• Exercise extreme caution with empirical antibiotics in IBD patients, as C. difficile infection mimics IBD flares 5, 6
• Empiric corticosteroid treatment without appropriate antibiotics for unrecognized C. difficile may precipitate clinical deterioration 5
• IBD patients with C. difficile have decreased efficacy with metronidazole and often require vancomycin 5, 6
• Prior history of colitis is the most significant risk factor for acquiring C. difficile in this population 5

Immunocompromised Patients

• While immunocompromised status is an exception to the general rule against empirical antibiotics, treatment decisions must weigh the risk of C. difficile infection 1, 2
• Continued antibiotic use (not directed against C. difficile) is associated with increased risk of CDI recurrence 1

Patients with Previous C. difficile Infection

• Avoid empirical antibiotics unless there is strong suspicion for severe CDI requiring immediate treatment while awaiting test results 1
• Continued use of antibiotics for infections other than CDI significantly increases the risk of CDI recurrence 1
• If antibiotics are absolutely necessary for another infection, use agents less frequently implicated in CDI: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline 1

Critical Pitfalls to Avoid

Antibiotic-Associated Diarrhea Risk

• All antibacterial agents can cause C. difficile-associated diarrhea (CDAD), which ranges from mild diarrhea to fatal colitis 7, 8, 9
• CDAD has been reported to occur over 2 months after antibiotic administration 7, 8
• Hypertoxin-producing strains cause increased morbidity and mortality and may be refractory to antimicrobial therapy, requiring colectomy 7, 8

Concurrent Medication Considerations

• Avoid antiperistaltic agents and opiates in infectious diarrhea, as these can worsen outcomes 1
• Consider discontinuing proton pump inhibitors (PPIs) when feasible, as there is clinical association between PPI use and CDI 1

Antimicrobial Resistance

• Routine empirical use should be avoided due to the cost of antibiotics and the potential to worsen antibiotic resistance of enteric pathogens 3
• Fluoroquinolone resistance in US patients without international travel remains low, but is significantly higher in travelers 1

When Empirical Treatment May Be Considered (Exceptions)

The following are the only scenarios where empirical antibiotics may be justified:

• Infants <3 months with suspected bacterial etiology (use ceftriaxone) 2
• Suspected enteric fever with sepsis (treat empirically after obtaining cultures) 1, 2
• Immunocompromised patients with severe illness and bloody diarrhea 1, 2
• Recent international travelers with fever ≥38.5°C and bloody diarrhea 2
• Confirmed Shigella (bacillary dysentery) 2
• Suspected severe C. difficile infection while awaiting test results 1

Diagnostic Approach Before Treatment

When considering antibiotics, obtain:

• Stool culture for Salmonella, Shigella, Campylobacter, Yersinia 2, 10
• C. difficile testing (toxin or PCR) 2, 10
• STEC testing (Shiga toxin or genes encoding it) is critical, as STEC O157:H7 requires special culture media (sorbitol-MacConkey agar) not used routinely 10
• Assessment of hydration status, fever pattern, presence of blood in stool, and duration of symptoms 1, 2