What is the most appropriate empiric antibiotic for acute dysentery in an otherwise healthy adult?

Best Antibiotic for Dysentery

Azithromycin is the first-line antibiotic for empiric treatment of acute dysentery in otherwise healthy adults, given as either a single 1-gram dose or 500 mg daily for 3 days. 1

Why Azithromycin is Preferred

The 2017 Journal of Travel Medicine guidelines provide a strong recommendation with high-level evidence that azithromycin should be the first-line agent for dysentery, regardless of geographic region. 1 This recommendation is driven by several critical factors:

• Fluoroquinolone resistance has become widespread globally, particularly among Campylobacter species (exceeding 90% resistance in some regions like Thailand), as well as emerging resistance in Shigella and Salmonella from India and sub-Saharan Africa 1
• Azithromycin demonstrated superiority over levofloxacin in achieving clinical cure in settings with high fluoroquinolone resistance 1
• It provides effective coverage for the most common dysentery pathogens: Shigella, Campylobacter, enteroinvasive E. coli, Aeromonas, Plesiomonas, and Yersinia enterocolitica 1, 2

Dosing Regimens

Two equally effective azithromycin regimens are available: 1

• Single 1-gram dose (better for compliance)
• 500 mg daily for 3 days (may have fewer gastrointestinal side effects)

The single-dose regimen can be split over the first day to potentially reduce nausea and vomiting, though this remains unproven 1

When Fluoroquinolones May Still Be Considered

Fluoroquinolones (ciprofloxacin 500-750 mg or levofloxacin 500 mg) remain second-line options in regions where local susceptibility patterns demonstrate retained efficacy 1, 3. However:

• The 2017 IDSA guidelines note that empiric therapy should be "either a fluoroquinolone or azithromycin, depending on local susceptibility patterns and travel history" 1
• Ciprofloxacin resistance is increasing globally, making it less reliable for empiric use 1, 3
• Treatment failures requiring rescue therapy occurred in 5% of fluoroquinolone-treated patients even in earlier studies 1

Critical Caveats and Pitfalls

Do NOT use antimotility agents (loperamide) in severe dysentery or high fever, despite older data suggesting safety when combined with antibiotics 4. The concern is potential worsening of invasive disease, though one 1993 study showed safety with ciprofloxacin in Shigella dysentery 4

Avoid antibiotics entirely if STEC O157 or Shiga toxin 2-producing strains are suspected, as antimicrobial therapy increases risk of hemolytic uremic syndrome 1

For immunocompromised patients with severe bloody diarrhea, empiric antibacterial treatment should be strongly considered even before pathogen identification 1

Side Effect Profile

Azithromycin is generally well-tolerated with minimal side effects 1:

• Gastrointestinal complaints (nausea 3%, vomiting <1%) are dose-related and exacerbated by the underlying infection 1
• Significantly safer than fluoroquinolones, which carry risks of tendon rupture, QT prolongation, and CNS effects 5

Alternative Agents (Not Recommended for Empiric Use)

Rifaximin should NOT be used for dysentery as it is poorly absorbed and ineffective for invasive disease 1, 3

Metronidazole is NOT appropriate for bacterial dysentery unless Entamoeba histolytica is confirmed (750 mg orally three times daily for 5-10 days for amebic dysentery) 6, 2

Third-generation cephalosporins may be considered in specific populations (infants <3 months, neurologic involvement) but are not first-line for typical adult dysentery 1