What is the dosage and treatment duration of Azithromycin for various bacterial infections?

Azithromycin Dosing and Treatment Duration

Azithromycin dosing varies significantly by indication, with the most common adult regimen being 500 mg on day 1 followed by 250 mg daily for days 2-5 (total 1.5 g), though sexually transmitted infections typically require a single 1 gram dose, and pediatric dosing is weight-based at 10 mg/kg on day 1 then 5 mg/kg daily for 4 days. 1

Adult Dosing Regimens

Respiratory Tract Infections

• Community-acquired pneumonia (mild): 500 mg on day 1, then 250 mg once daily on days 2-5 1
• Acute bacterial exacerbations of COPD: Either 500 mg daily for 3 days OR 500 mg on day 1 followed by 250 mg daily on days 2-5 1
• Acute bacterial sinusitis: 500 mg daily for 3 days 1
• Pharyngitis/tonsillitis (second-line): 500 mg on day 1, then 250 mg daily on days 2-5 1
• Atypical pneumonia (Mycoplasma, Chlamydia, Coxiella): Either 500 mg daily for 3 days OR the standard 5-day regimen, both equally effective 2

Sexually Transmitted Infections

• Non-gonococcal urethritis/cervicitis (Chlamydia): Single 1 gram dose 1, 3
• Gonococcal urethritis/cervicitis: Single 2 gram dose 1
• Chancroid: Single 1 gram dose 1

The single-dose regimen for chlamydial infections provides therapeutic tissue concentrations for approximately 10 days due to azithromycin's prolonged tissue half-life, with the major advantage being improved compliance through directly observed therapy 3

Skin and Soft Tissue Infections

• Uncomplicated infections: 500 mg on day 1, then 250 mg daily on days 2-5 1
• Duration is approximately 7 days depending on clinical response 4

Specialized Indications

• Cat scratch disease: 500 mg on day 1, then 250 mg daily for 4 additional days (patients >45 kg) 3
• Legionnaires' disease (hospitalized): 500 mg IV daily for 2-7 days, then oral to complete 7-10 days total 5
• Legionnaires' disease (outpatient): 500 mg on day 1, then 250 mg daily for 4 days 5
• Disseminated MAC in AIDS: 250 mg daily with ethambutol ± rifabutin 3
• MAC prophylaxis in AIDS (CD4 <50): 1,200 mg once weekly 3

Pediatric Dosing Regimens

Standard Respiratory Infections

• Community-acquired pneumonia: 10 mg/kg on day 1 (max 500 mg), then 5 mg/kg daily on days 2-5 (max 250 mg/day) 1, 6
• Acute otitis media: Three options available 1:
  • 30 mg/kg as single dose (1-day regimen)
  • 10 mg/kg once daily for 3 days
  • 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5
• Acute bacterial sinusitis: 10 mg/kg once daily for 3 days 1
• Pharyngitis/tonsillitis: 12 mg/kg once daily for 5 days (ages ≥2 years) 1, 6

Important caveat: The higher 12 mg/kg/day dose for pharyngitis is necessary because standard dosing results in more recurrence of streptococcal infection compared to penicillin 6

Atypical Pathogens in Children

• Mycoplasma pneumoniae or Chlamydia pneumoniae: 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 5

Pertussis

• Infants <6 months: 10 mg/kg daily for 5 days 3
• Infants and children ≥6 months: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) daily on days 2-5 3

Special Populations

• Neonatal chlamydial conjunctivitis: 20 mg/kg once daily for 3 days 3
• Cat scratch disease (<45 kg): 10 mg/kg on day 1, then 5 mg/kg daily for 4 days 3

Administration Considerations

• Food interactions: Can be taken with or without food 1, though coadministration with a large meal may reduce absorption by up to 50% 7
• Antacid interactions: Aluminum or magnesium-containing antacids reduce absorption; separate administration 3
• Directly observed first dose: Recommended to maximize compliance, particularly for STI treatment 3
• Vomiting in children: If a child vomits within 30 minutes of receiving the 30 mg/kg single dose for otitis media, re-dosing at the same total dose has been studied, though safety data are limited 1

Cardiac Safety Monitoring

Before initiating azithromycin in patients with cardiac risk factors, obtain a baseline ECG to assess QTc interval 8, 5

• Avoid azithromycin if QTc >450 ms (men) or >470 ms (women) 8, 5
• This is critical because azithromycin can prolong the QT interval and increase risk of torsades de pointes 8

Renal and Hepatic Dosing

• Renal impairment (GFR 10-80 mL/min): No dosage adjustment needed 1
• Severe renal impairment (GFR <10 mL/min): Use with caution; AUC increases 35% 1
• Hepatic impairment: No established dosing recommendations; pharmacokinetics not studied 1

Common Pitfalls and Caveats

Resistance Concerns

• Macrolide resistance varies geographically and temporally, particularly for Group A Streptococcus 5
• Not first-line for strep pharyngitis; use only as alternative in penicillin-allergic patients 5
• Azithromycin's long half-life (68 hours) creates a prolonged "window" of subinhibitory concentrations (14-20 days for complete elimination), potentially selecting for resistant organisms 4
• Studies show azithromycin-resistant S. pneumoniae carriage rates spike to 55% at 2-3 weeks post-treatment, though this decreases to 6% by 6 months 4

Clinical Efficacy Considerations

• H. influenzae in COPD exacerbations: Some patients may be refractory to azithromycin therapy; physician vigilance required 9
• Breakthrough bacteremia: Low serum concentrations (despite high tissue levels) may allow breakthrough bacteremia in severely ill patients 9
• STI treatment: Patients should abstain from sexual intercourse for 7 days after completing therapy 3

Tolerability

• Gastrointestinal side effects (nausea, vomiting, abdominal pain, diarrhea) occur in approximately 3% of patients but are less frequent than with erythromycin 8, 7, 9
• Better tolerated than amoxicillin/clavulanic acid in pediatric populations 6
• Common side effects include abdominal discomfort, diarrhea, nausea, vomiting, headache, and dizziness 3

Pregnancy and Neonates

• FDA Pregnancy Category B 3
• Preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 3
• Single 1 gram dose is an alternative regimen for chlamydial infections in pregnancy 3

Antimicrobial Stewardship Principles

• Limit antibiotic exposure whenever possible to minimize resistance development 8
• Consider viral etiology of many respiratory infections before prescribing 8, 5
• Use shortest effective duration to minimize exposure of pathogens and normal microbiota 8
• Assess clinical response at days 5-7; improvement of symptoms should be evident 8