What is the recommended dosage and treatment duration of azithromycin for bacterial infections?

Azithromycin Dosing for Bacterial Infections

For most common bacterial infections in adults, azithromycin is dosed as 500 mg on day 1, followed by 250 mg once daily on days 2-5 (the standard "Z-pack"), while sexually transmitted infections typically require a single 1 gram dose. 1

Standard Adult Dosing Regimens

Respiratory Tract Infections

• Community-acquired pneumonia (mild severity), pharyngitis/tonsillitis (second-line), and uncomplicated skin/skin structure infections: 500 mg as a single dose on day 1, followed by 250 mg once daily on days 2-5 (total 5-day course) 1
• Acute bacterial exacerbations of COPD: Either 500 mg once daily for 3 days OR the standard 5-day regimen (500 mg day 1, then 250 mg days 2-5) 1
• Acute bacterial sinusitis: 500 mg once daily for 3 days 1
• Total treatment duration for community-acquired pneumonia should be 7-10 days 2

Sexually Transmitted Infections

• Non-gonococcal urethritis and cervicitis (Chlamydia trachomatis): Single 1 gram dose 1, 3
• Gonococcal urethritis and cervicitis: Single 2 gram dose, though azithromycin should NOT be used as monotherapy for gonorrhea—must be combined with ceftriaxone due to resistance concerns 4
• Genital ulcer disease (chancroid): Single 1 gram dose 1

Specialized Indications

• Cat scratch disease (>45 kg): 500 mg on day 1, then 250 mg daily for 4 additional days 3
• Disseminated MAC disease in AIDS patients: 250 mg daily with ethambutol, with or without rifabutin 3
• MAC prophylaxis in AIDS (CD4 <50 cells/μL): 1,200 mg once weekly 3
• Travelers' diarrhea/dysentery: Either single 1 gram dose or 500 mg daily for 3 days (azithromycin is first-line for dysentery due to widespread fluoroquinolone resistance in Campylobacter and Shigella) 4

Pediatric Dosing Regimens

Acute Otitis Media (≥6 months)

Three options available 1:

• Single-dose regimen: 30 mg/kg as a single dose (maximum 1500 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 once daily on days 2-5

Community-Acquired Pneumonia (≥6 months)

• 10 mg/kg as a single dose on day 1 (maximum 500 mg), followed by 5 mg/kg once daily on days 2-5 (maximum 250 mg/day) 1, 4

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
• The higher dose of 12 mg/kg is necessary because azithromycin results in more recurrence of streptococcal pharyngitis compared to penicillin V at lower doses 5

Pertussis

• Infants <6 months: 10 mg/kg per day for 5 days 3
• Infants and children ≥6 months: 10 mg/kg (maximum 500 mg) on day 1, followed by 5 mg/kg per day (maximum 250 mg) on days 2-5 3

Special Pediatric Populations

• Chlamydial conjunctivitis in neonates: 20 mg/kg body weight per day orally once daily for 3 days 3

Administration Considerations

• Azithromycin can be taken with or without food 1
• Avoid concurrent administration with aluminum- or magnesium-containing antacids, as they reduce absorption by up to 50%—separate by at least 2 hours 4, 6
• Directly observed first dose is recommended to maximize compliance, particularly for single-dose regimens 3
• Dispense medication on-site when possible to improve adherence 3

Critical Safety Warnings and Contraindications

Cardiac Risks

• Azithromycin can cause fatal cardiac arrhythmias, including torsades de pointes—avoid or use with extreme caution in patients with known QT prolongation or history of torsades de pointes 2

Resistance Concerns

• Consider local resistance patterns, as high macrolide resistance may favor alternative agents 2
• Azithromycin's long half-life (68 hours) creates a prolonged 14-20 day "window" of subinhibitory drug concentrations that may promote resistance development 7, 2
• Following a single dose, carriage rates of azithromycin-resistant S. pneumoniae increased from 2% pre-treatment to 55% at 2-3 weeks, though this declined to 6% by 6 months 7

Tuberculosis Screening

• Empiric azithromycin for pneumonia may delay tuberculosis diagnosis—consider TB screening in high-risk populations before initiating therapy 2

Pregnancy and Infants

• Azithromycin is FDA Pregnancy Category B and considered safe in pregnancy 3, 4
• Azithromycin is preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 3, 4

Pharmacodynamic Principles

• 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
• Tissue concentrations far exceed serum concentrations due to extensive intracellular accumulation, with a large volume of distribution (23 L/kg) 6, 8
• Terminal elimination half-life is up to 5 days, allowing once-daily dosing and short treatment courses 6, 8

Common Adverse Effects

• Gastrointestinal symptoms are most common: abdominal discomfort/pain, diarrhea, nausea, vomiting 3, 4
• Other adverse effects include: headache and dizziness 3
• Gastrointestinal tolerance is better than erythromycin 6, 8
• Adverse events are generally mild to moderate in severity 5, 4

When NOT to Use Azithromycin

• Doxycycline is preferred for chlamydial and non-gonococcal urethritis; azithromycin should only be used if doxycycline fails, is contraindicated, or adherence concerns exist 2
• Amoxicillin-clavulanate shows superior efficacy compared to macrolides in head-to-head trials for acute bacterial sinusitis 2
• Beta-lactams remain first-line for hospitalized patients with community-acquired pneumonia 2
• For macrolide-resistant Mycoplasma genitalium, switch to moxifloxacin 400 mg daily for 7-14 days 4

Special Renal and Hepatic Considerations

• No dosage adjustment needed for renal impairment (GFR ≤80 mL/min), but use caution in severe renal impairment (GFR <10 mL/min) where AUC increases 35% 1
• No dosage adjustment recommendations can be made for hepatic impairment due to lack of pharmacokinetic data 1