What empiric antibiotics should be given for a patient with acute febrile diarrheal illness and leukocytosis (white blood cell count 18 × 10⁹/L)?

Empiric Antibiotic Treatment for Acute Febrile Diarrhea with Leukocytosis

Start azithromycin 500 mg once daily for 3 days immediately after obtaining stool culture and Shiga toxin testing. 1, 2

Immediate Diagnostic Steps Before Treatment

• Obtain stool studies urgently: culture, Shiga toxin testing, and consider ova/parasites given the leukocytosis (WCC 18.05 × 10⁹/L) which suggests invasive bacterial infection 1, 2
• Rule out STEC (Shiga toxin-producing E. coli) first: This is critical because antibiotics are absolutely contraindicated in STEC O157 and Shiga toxin 2-producing strains, as they significantly increase hemolytic uremic syndrome risk 3, 1, 2
• Assess for high-risk features: The combination of leukocytosis (18.05) with presumed fever meets criteria for empiric treatment while awaiting culture results 1, 2

First-Line Antibiotic Choice

Azithromycin is the preferred empiric agent over fluoroquinolones due to widespread fluoroquinolone resistance exceeding 90% in many regions, particularly for Campylobacter and Shigella 1, 2, 4

Dosing Options:

• Standard regimen: Azithromycin 500 mg once daily for 3 days 1, 2, 4
• Severe cases with dysentery: Single 1-gram dose 1, 2, 4

Second-Line Alternatives (Only if Azithromycin Unavailable)

• Fluoroquinolones: Ciprofloxacin 500 mg twice daily for 3 days OR levofloxacin 750 mg once daily, but only if local resistance patterns support use 1, 2
• Note: The CDC and WHO recommend fluoroquinolones only when azithromycin is unavailable due to resistance concerns 1

Critical Contraindications

Never give antibiotics if STEC is confirmed or suspected (particularly with bloody diarrhea without fever), as fluoroquinolones, β-lactams, TMP-SMX, and metronidazole all increase hemolytic uremic syndrome risk 3, 2

Red Flags for STEC:

• Bloody diarrhea with minimal or absent fever 3
• Recent consumption of undercooked beef or contaminated produce 3
• If STEC suspected: Hold antibiotics until Shiga toxin testing returns negative 1, 2

Specific Pathogen Considerations

The most likely pathogens with fever and leukocytosis are Salmonella, Campylobacter, Shigella, or C. difficile 3

• For Shigella: Azithromycin 500 mg twice daily for 3 days is first-line; ceftriaxone 100 mg/kg/day is alternative 2
• For Campylobacter: Azithromycin 500 mg daily for 3 days due to high fluoroquinolone resistance 2
• For non-typhoidal Salmonella: Generally avoid antibiotics unless severe infection, age <6 months or >50 years, or immunocompromised 3, 2
• For C. difficile: Consider if recent antibiotic exposure within 60 days; treat with metronidazole or vancomycin, not azithromycin 3, 2

Management Algorithm

1. Obtain stool culture and Shiga toxin testing immediately 1, 2
2. Assess severity: Fever ≥38.5°C, bloody stools, signs of sepsis, or immunocompromised status warrant empiric treatment 1, 2
3. Start azithromycin 500 mg daily for 3 days if high-risk features present and STEC not suspected 1, 2
4. Modify or discontinue antibiotics when culture results identify specific pathogen 2
5. Reassess at 48-72 hours if no improvement: consider antibiotic resistance, inadequate rehydration, or non-infectious causes 2

Essential Supportive Care

Rehydration is the cornerstone of all diarrhea management, regardless of antibiotic use 2

• Reduced osmolarity oral rehydration solution (ORS) containing 50-90 mEq/L sodium for mild-moderate dehydration 2
• Intravenous fluids for severe dehydration, shock, altered mental status, or ileus 2

Common Pitfalls to Avoid

• Do not use fluoroquinolones as first-line: Resistance rates are too high, making azithromycin superior 1, 2, 4
• Do not give antibiotics empirically for bloody diarrhea without ruling out STEC first: Always obtain Shiga toxin testing 1, 2
• Do not treat non-typhoidal Salmonella routinely: Only treat high-risk patients 3, 2
• Do not use rifaximin if invasive pathogens suspected: It is ineffective against Campylobacter, Salmonella, and Shigella 2, 4
• Monitor for treatment failure: If no response within 48-72 hours, reassess for complications and consider hospitalization 2