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 regimens being 500 mg on day 1 followed by 250 mg daily for days 2-5 (total 1.5g over 5 days) for respiratory infections, or a single 1-gram dose for sexually transmitted infections like chlamydia. 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 1
• Total treatment duration: 5 days
• 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
• Both regimens deliver 1.5g total dose

Acute Bacterial Sinusitis:

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

Pharyngitis/Tonsillitis (second-line therapy):

• 500 mg on day 1, then 250 mg daily on days 2-5 1
• Important caveat: Not first-line for strep pharyngitis due to macrolide resistance concerns 4

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 therapy is recommended to maximize compliance 2
• Patients must abstain from sexual intercourse for 7 days after treatment 2

Gonococcal Urethritis and Cervicitis:

• Single 2-gram dose 1
• Note: This is no longer recommended as monotherapy due to resistance; current guidelines favor ceftriaxone-based regimens

Genital Ulcer Disease (Chancroid):

• Single 1-gram dose 1

Skin and Soft Tissue Infections

Uncomplicated Skin/Skin Structure Infections:

• 500 mg on day 1, followed by 250 mg once daily on days 2-5 1
• Duration approximately 7 days depending on clinical response 5

Cat Scratch Disease:

• 500 mg on day 1, followed by 250 mg daily for 4 additional days (patients >45 kg) 2
• For patients <45 kg: 10 mg/kg on day 1, then 5 mg/kg for 4 more days 2

Specialized Indications

Disseminated MAC Disease (AIDS patients):

• 250 mg daily with ethambutol, with or without rifabutin 2

MAC Prophylaxis (AIDS patients with CD4 <50 cells/μL):

• 1,200 mg once weekly 2

Travelers' Diarrhea with Dysentery:

• Single 1-gram dose OR 500 mg daily for 3 days 3

Legionnaires' Disease:

• Hospitalized: 500 mg IV daily for 2-7 days, then oral to complete 7-10 days total 4
• Non-hospitalized (mild): 500 mg on day 1, then 250 mg daily for 4 additional days 4

Pediatric Dosing

Acute Otitis Media (≥6 months)

Three dosing options: 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 daily on days 2-5

Community-Acquired Pneumonia (≥6 months)

• 10 mg/kg on day 1, followed by 5 mg/kg daily on days 2-5 1
• Alternative for atypical pathogens (Mycoplasma, Chlamydophila): 10 mg/kg on days 1-2, then transition to oral 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

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
• 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

Administration Considerations

Timing with Food:

• Azithromycin tablets can be taken with or without food 1
• Avoid taking with large meals, as this may reduce absorption by up to 50% 6

Antacid Interactions:

• If taken with aluminum or magnesium-containing antacids, absorption may be reduced 2
• Separate administration by at least 2 hours

Vomiting in Pediatric Patients:

• If a child vomits within 30 minutes of receiving the 30 mg/kg single dose, re-dosing at the same total dose has been studied in clinical trials 1

Special Populations

Renal Insufficiency:

• No dosage adjustment needed for GFR 10-80 mL/min 1
• Caution in severe renal impairment (GFR <10 mL/min): AUC increases 35%; use with caution 1

Hepatic Insufficiency:

• Pharmacokinetics not established; no specific dose adjustment recommendations available 1
• Use with caution given hepatic metabolism and biliary excretion 6

Pregnancy:

• FDA Pregnancy Category B 2
• Single 1-gram dose is an alternative regimen for chlamydial infections in pregnancy 2

Age and Gender:

• No dosage adjustment recommended based on age or gender 1

Critical Safety Considerations

Cardiac Monitoring:

• Obtain baseline ECG in patients with cardiac risk factors before initiating therapy 4, 3
• Avoid azithromycin if QTc interval is >450 ms (men) or >470 ms (women) 4, 3
• Azithromycin can prolong QT interval and increase risk of torsades de pointes

Common Side Effects:

• Gastrointestinal: abdominal discomfort/pain, diarrhea, nausea, vomiting (occurs in ~3% of patients) 2, 3
• Headache and dizziness 2
• Better GI tolerance than erythromycin 6, 7

Pharmacodynamic Principles

Mechanism of Action:

• Azithromycin exhibits time-dependent killing with moderate to prolonged persistent effects 5
• The pharmacodynamic parameter correlating with efficacy is the AUC/MIC ratio (target approximately 25) rather than time above MIC 5

Unique Pharmacokinetics:

• Terminal elimination half-life: 68 hours (approximately 3 days) 5
• Total elimination from body occurs over 14-20 days (5-7 half-lives) 5
• Extensive tissue distribution with intracellular accumulation 6, 8
• Low serum concentrations but high tissue concentrations 8, 7

Resistance Concerns and Antimicrobial Stewardship

Resistance Selection:

• The prolonged half-life creates an extended "window" of subinhibitory concentrations (14-20 days), potentially selecting for resistant organisms 5
• Single-dose azithromycin (20 mg/kg) increased carriage of azithromycin-resistant S. pneumoniae from 2% pre-treatment to 55% at 2-3 weeks, declining to 6% at 6 months 5

Geographic Resistance Patterns:

• Macrolide resistance varies geographically and temporally, particularly for group A streptococcus 4
• Not recommended as first-line for strep pharyngitis 4

Stewardship Principles:

• Limit antibiotic exposure whenever possible 3
• Consider viral etiology before prescribing 3, 4
• Use shortest effective duration 3
• Assess clinical response at days 5-7 3

Common Pitfalls

1. Breakthrough bacteremia: Low serum concentrations may allow breakthrough bacteremia in severely ill patients, though tissue concentrations are typically adequate for respiratory infections 8

2. H. influenzae in COPD: Some patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to azithromycin therapy; physician vigilance is required 8

3. Compliance advantage: The primary advantage over alternatives like doxycycline is short duration and once-daily dosing, significantly improving adherence 2

4. Dispensing strategy: Dispense medication on-site when possible and use directly observed first dose to maximize compliance 2