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 (age ≥2 years) 1, 6

Critical caveat: The higher 12 mg/kg/day dose for 5 days is necessary for streptococcal pharyngitis because standard dosing results in more recurrences compared to penicillin 6

Atypical Pathogens (Pediatric)

• 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

Important note: Azithromycin is preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 3

Special Pediatric Populations

• Chlamydial conjunctivitis in neonates: 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 interaction: Can be taken with or without food 1
• Antacid interaction: Avoid concurrent administration with aluminum or magnesium-containing antacids as absorption may be reduced 3
• Directly observed first dose: Recommended to maximize compliance, particularly for STI treatment 3
• Vomiting in pediatrics: If a child vomits within 30 minutes of 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 7, 5

• Contraindication: Avoid if QTc >450 ms (men) or >470 ms (women) 7, 5
• Risk factors requiring ECG: History of arrhythmias, heart failure, electrolyte abnormalities, concurrent QT-prolonging medications 5

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 Antimicrobial Stewardship

Resistance Concerns

• Prolonged subinhibitory concentrations: Azithromycin's 68-hour half-life results in 14-20 days for complete elimination, creating a prolonged "window" for potential selection of resistant organisms 4
• Macrolide resistance: Varies geographically and temporally, particularly for Group A Streptococcus and S. pneumoniae 5
• Not first-line for strep pharyngitis: Should be reserved as alternative in penicillin-allergic patients 5

Clinical Monitoring

• Assess response at days 5-7: Improvement of symptoms should be evident; if not, consider alternative diagnosis or resistant pathogen 7
• H. influenzae in COPD: Some patients may be refractory to azithromycin therapy, requiring physician vigilance 8
• Breakthrough bacteremia: Low serum concentrations may allow breakthrough in severely ill patients, though tissue concentrations are typically adequate 8

Adverse Effects

• Gastrointestinal symptoms: Nausea, vomiting, abdominal pain, diarrhea occur in approximately 3% of patients but are less frequent than with erythromycin 7, 9
• Pregnancy: FDA Category B; safe alternative in pregnancy 3

STI-Specific Considerations

• Sexual abstinence: Patients treated for STIs should abstain for 7 days after completing therapy to prevent transmission 3
• Partner treatment: Ensure concurrent treatment of sexual partners 3

Pharmacodynamic Principles

Azithromycin exhibits time-dependent killing with moderate to prolonged persistent effects, with the AUC:MIC ratio (target ≈25) being the pharmacodynamic parameter that correlates with efficacy rather than time above MIC 4. This allows for once-daily dosing and short treatment courses despite relatively low serum concentrations, as the drug achieves extensive tissue distribution with intracellular accumulation and slow release 9, 8.