Azithromycin Dosing and Treatment Duration
Azithromycin dosing varies significantly by infection type, with the most common regimen being 500 mg on day 1 followed by 250 mg daily on days 2-5 for respiratory infections, while sexually transmitted infections typically require a single 1-gram dose. 1
Adult Dosing by Indication
Respiratory Tract Infections
Community-Acquired Pneumonia (mild severity):
- 500 mg as a single dose on day 1, followed by 250 mg once daily on days 2-5 (total 5 days) 1
- This is the standard "Z-pack" regimen 2
Acute Bacterial Exacerbations of COPD:
Acute Bacterial Sinusitis:
- 500 mg once daily for 3 days 1
Pharyngitis/Tonsillitis (second-line therapy):
- 500 mg on day 1, then 250 mg daily on days 2-5 1
- Note: Azithromycin is not first-line for strep pharyngitis due to variable macrolide resistance; reserve for penicillin-allergic patients 3
Sexually Transmitted Infections
Non-gonococcal urethritis and cervicitis (Chlamydia):
- Single 1-gram dose orally 1, 2
- This provides therapeutic tissue concentrations for approximately 10 days due to azithromycin's prolonged tissue half-life 2
- Directly observed first dose maximizes compliance 2
- Patients must abstain from sexual intercourse for 7 days after completing therapy 2
Gonococcal urethritis and cervicitis:
- Single 2-gram dose 1
Genital ulcer disease (chancroid):
- Single 1-gram dose 1
Specialized Infections
Cat Scratch Disease:
- 500 mg on day 1, followed by 250 mg daily for 4 additional days (patients >45 kg) 2
Legionnaires' Disease:
- Hospitalized patients: 500 mg IV daily for 2-7 days, then transition to oral to complete 7-10 days total 3
- Non-hospitalized (mild disease): 500 mg on day 1, then 250 mg daily for 4 additional days 3
Disseminated MAC Disease (AIDS patients):
- 250 mg daily with ethambutol, with or without rifabutin 2
MAC Prophylaxis (AIDS, CD4 <50 cells/μL):
- 1,200 mg once weekly 2
Travelers' Diarrhea with Dysentery:
Pediatric Dosing by Indication
Acute Otitis Media (≥6 months)
Three regimen options: 1
- Single-dose: 30 mg/kg as a single dose (maximum 1,500 mg)
- 3-day regimen: 10 mg/kg once daily for 3 days
- 5-day regimen: 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5
Community-Acquired Pneumonia (≥6 months)
- 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 1
- For atypical pathogens (Mycoplasma, Chlamydophila): Same dosing 3
Acute Bacterial Sinusitis (≥6 months)
- 10 mg/kg once daily for 3 days 1
Pharyngitis/Tonsillitis (≥2 years)
- 12 mg/kg once daily for 5 days (maximum 500 mg/day) 1
Pertussis
- Infants <6 months: 10 mg/kg per day for 5 days 2
- Infants and children ≥6 months: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg per day (max 250 mg) on days 2-5 2
- Azithromycin is preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 2
Chlamydial Conjunctivitis (Neonates)
- 20 mg/kg per day orally once daily for 3 days 2
Cat Scratch Disease (<45 kg)
- 10 mg/kg on day 1, then 5 mg/kg for 4 additional days 2
Administration Considerations
Food Interactions:
- Azithromycin tablets and suspension can be taken with or without food 1
- However, taking with a large meal may reduce absorption by up to 50% 5
Antacid Interactions:
- Aluminum or magnesium-containing antacids may reduce absorption 2
- Separate administration if concurrent use is necessary
Vomiting in Pediatric Patients:
- 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 in clinical trials 1
Critical Safety Considerations
Cardiac Monitoring
Before initiating azithromycin, obtain a baseline ECG in patients with cardiac risk factors: 4, 3
- Avoid azithromycin if QTc >450 ms (men) or >470 ms (women) 4, 3
- Azithromycin can prolong the QT interval and increase risk of torsades de pointes
Special Populations
Renal Insufficiency:
- No dosage adjustment needed for GFR 10-80 mL/min 1
- Exercise caution in severe renal impairment (GFR <10 mL/min) as AUC increases 35% 1
Hepatic Insufficiency:
- Pharmacokinetics not established; no specific dose adjustment recommendations available 1
- Use with caution as metabolism is predominantly hepatic 5
Pregnancy:
- FDA Pregnancy Category B 2
- Single 1-gram dose is an alternative regimen for chlamydial infections in pregnancy 2
Common Adverse Effects
- Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea) occur in approximately 3% of patients 4
- GI tolerance is superior to erythromycin 5, 6
- Headache and dizziness may occur 2
Antimicrobial Stewardship and Resistance Concerns
Key Resistance Considerations:
- Macrolide resistance varies geographically and temporally, particularly for Group A Streptococcus and Streptococcus pneumoniae 3
- Erythromycin-resistant organisms are also resistant to azithromycin 6
- Azithromycin's long half-life (68 hours) creates an extended "window" of subinhibitory concentrations (14-20 days for complete elimination), potentially selecting for resistant strains 7
- Single-dose azithromycin (20 mg/kg) increased carriage of azithromycin-resistant S. pneumoniae from 2% pre-treatment to 55% at 2-3 weeks, though this declined to 6% by 6 months 7
Stewardship Principles:
- Limit antibiotic exposure whenever possible 4
- Consider viral etiology before prescribing for respiratory infections 4
- Use the shortest effective duration 4
- Assess clinical response at days 5-7; improvement of symptoms indicates adequate therapy 4
Pharmacodynamic Rationale
Azithromycin exhibits time-dependent killing with a prolonged post-antibiotic effect: 7
- The pharmacodynamic parameter correlating with efficacy is the AUC/MIC ratio (target approximately 25) rather than time above MIC 7
- Extensive tissue distribution and intracellular accumulation result in tissue concentrations far exceeding serum levels 5, 6
- Volume of distribution is 23 L/kg with peak serum levels of only 0.4 mcg/mL, but tissue concentrations are substantially higher 5
- Terminal elimination half-life extends up to 5 days, allowing once-daily or even single-dose regimens 5, 6