Azithromycin Dosing for Pediatric Shigella Dysentery
Direct Recommendation
For Shigella dysentery in children, azithromycin should be dosed at 10 mg/kg (maximum 500 mg) once daily for 5 days, though emerging resistance patterns in many regions make ciprofloxacin or ceftriaxone potentially more reliable first-line choices depending on local susceptibility data. 1
Standard Dosing Regimen
The established azithromycin regimen for pediatric shigellosis is 10 mg/kg once daily for 5 days (not the respiratory infection regimen of front-loading day 1 followed by lower doses). 1
For children ≥6 months, this translates to a flat 10 mg/kg daily dose throughout the 5-day course, with a maximum single dose of 500 mg for adolescents and larger children. 2, 1
Weight-band dosing can be applied for practical administration:
Critical Resistance Considerations
Azithromycin resistance among Shigella species is alarmingly high in multiple regions, with reported resistance rates of 20.7–91.7% for S. flexneri and S. dysenteriae in Iranian pediatric populations. 3
A 2020 Iranian study documented 25.5% azithromycin resistance and 43.6% ceftriaxone resistance among Shigella isolates from children, leading authors to recommend against empirical use of either agent. 4
Ciprofloxacin maintains the lowest resistance rates (2.6–7% across Shigella species in recent Iranian data), making fluoroquinolones the most reliable empirical choice in high-resistance settings despite traditional pediatric concerns. 3, 4
In settings where local susceptibility data confirm azithromycin susceptibility, it remains an effective oral option with clinical success rates of 82% and bacteriologic success of 94% in controlled trials of multidrug-resistant shigellosis. 1
Laboratory and Clinical Monitoring Pitfalls
Azithromycin susceptibility testing for Shigella sonnei produces a dual-zone phenomenon on disk diffusion and E-test, creating interpretation challenges; laboratories must use the inner zone for accurate MIC determination to avoid false susceptibility reports. 5
Clinical improvement should occur within 48–72 hours; persistence of frank dysentery beyond 72 hours or >6 stools/day on day 5 constitutes treatment failure and mandates culture-directed therapy adjustment. 2, 1
Bacteriologic failure is defined as continued Shigella isolation after study day 2 of therapy. 1
Pharmacokinetic Rationale
Peak serum azithromycin concentrations approximate the MIC of susceptible Shigella strains (unlike ciprofloxacin, which achieves serum levels 28× the MIC), but stool concentrations exceed 200× the MIC, providing the therapeutic effect at the site of infection. 1
The once-daily dosing schedule improves adherence compared to four-times-daily erythromycin or twice-daily clarithromycin. 2
Administration Guidance
Azithromycin may be taken with or without food. 2
Separate administration from aluminum- or magnesium-containing antacids by at least 2 hours to prevent reduced absorption. 2
The pediatric oral suspension formulation should be reconstituted with water before administration for children unable to swallow tablets. 2
When to Choose Alternative Agents
If local resistance data show >10% azithromycin resistance among Shigella isolates, empirical ciprofloxacin is preferred despite traditional pediatric fluoroquinolone restrictions, as treatment failure of dysentery carries higher morbidity risk than theoretical musculoskeletal concerns. 3, 4
For severe disease requiring parenteral therapy or documented azithromycin resistance, ceftriaxone or ciprofloxacin (if susceptible) should be used rather than azithromycin. 4
Obtain stool culture and susceptibility testing before initiating therapy when feasible to guide definitive treatment, given the unpredictable and regionally variable resistance patterns. 3, 4, 5