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

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:

• Option 1: 500 mg once daily for 3 days 1
• Option 2: 500 mg on day 1, then 250 mg daily on days 2-5 1

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:

• Option 1: Single 1-gram dose 4
• Option 2: 500 mg daily for 3 days 4

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 Issues:

• Azithromycin has a 68-hour half-life, resulting in prolonged subinhibitory concentrations for 14-20 days after administration 7
• This extended "window" of subinhibitory drug levels may promote selection of resistant organisms 7
• Studies show azithromycin-resistant S. pneumoniae carriage rates increased from 2% pre-treatment to 55% at 2-3 weeks post-treatment, though declining to 6% by 6 months 7
• Macrolide resistance varies geographically and temporally, particularly for group A streptococcus 3

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 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
• Despite low serum concentrations (peak ~0.4 mcg/mL), azithromycin achieves extensive tissue distribution with intracellular accumulation 5, 6
• Large volume of distribution (23 L/kg) results in tissue concentrations exceeding those of erythromycin 5, 6
• Tissue concentrations are more important than serum levels for treating respiratory and other infections 6

Common Pitfalls

• Do not use azithromycin as first-line for streptococcal pharyngitis due to resistance concerns 3
• Breakthrough bacteremia may occur in severely ill patients due to low serum concentrations; consider alternative agents for serious infections requiring high serum levels 6
• Some patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to azithromycin therapy, requiring physician vigilance 6
• Always dispense medication on-site when possible to improve adherence, particularly for single-dose STI regimens 2