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 on days 2-5 for respiratory infections, while sexually transmitted infections typically require a single 1-gram dose. 1

Standard Adult Dosing by Indication

Respiratory Tract Infections

• Community-acquired pneumonia (mild): 500 mg on day 1, then 250 mg once daily on days 2-5 (total 5 days) 1
• Acute bacterial exacerbations of COPD: Either 500 mg daily for 3 days OR 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): 500 mg on day 1, then 250 mg daily on days 2-5 1
• Upper respiratory infections: 500 mg daily for 3 days or the standard 5-day regimen 2

Severe Community-Acquired Pneumonia (Hospitalized)

• 500 mg IV daily for 2-5 days, followed by oral 500 mg daily to complete 7-10 days total 3

Sexually Transmitted Infections

• Non-gonococcal urethritis/cervicitis (Chlamydia): Single 1-gram dose 1, 3
  • This provides therapeutic tissue concentrations for approximately 10 days due to azithromycin's prolonged tissue half-life 3
  • The single-dose regimen offers critical advantages in compliance and allows directly observed therapy 3
• Gonococcal urethritis/cervicitis: Single 2-gram dose 1
  • Critical caveat: Azithromycin should NOT be used as monotherapy for gonorrhea due to widespread resistance; must be combined with ceftriaxone 3
• Genital ulcer disease (chancroid): Single 1-gram dose 1

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

Special Infections

• Cat scratch disease (>45 kg): 500 mg on day 1, then 250 mg daily for 4 additional days 3
• Legionnaires' disease (hospitalized): 500 mg IV daily for 2-7 days, then oral to complete 7-10 days total 5
• Legionnaires' disease (non-hospitalized): 500 mg on day 1, then 250 mg daily for 4 additional days 5
• Travelers' diarrhea with dysentery: Single 1-gram dose or 500 mg daily for 3 days 2

Long-Term Prophylactic Regimens

• Bronchiectasis with ≥3 exacerbations/year: 500 mg three times weekly for at least 6 months 3
  • Alternative: 250 mg daily 3
• Disseminated MAC disease in AIDS: 250 mg daily with ethambutol, with or without rifabutin 3
• MAC prophylaxis in AIDS (CD4 <50): 1,200 mg once weekly 3
• Bronchiolitis obliterans syndrome (lung transplant): 250 mg daily for 5 days, then 250 mg three times weekly for at least 3 months 3

Pediatric Dosing

Standard Pediatric Regimens (≥6 months)

• 5-day regimen (otitis media, community-acquired pneumonia): 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 1
• 3-day regimen (otitis media, acute bacterial sinusitis): 10 mg/kg once daily for 3 days 1
• 1-day regimen (otitis media only): 30 mg/kg as a single dose 1
• Pharyngitis/tonsillitis (≥2 years): 12 mg/kg once daily for 5 days 1

Specific Pediatric Infections

• Mycoplasma pneumoniae: 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 5
• Chlamydia trachomatis/Chlamydophila pneumoniae: Same as Mycoplasma dosing 5
• Pertussis (<6 months): 10 mg/kg daily for 5 days 3
• Pertussis (≥6 months): 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg daily (max 250 mg) on days 2-5 3
• Cat scratch disease (<45 kg): 10 mg/kg on day 1, then 5 mg/kg daily for 4 additional days 3
• Chlamydial conjunctivitis (neonates): 20 mg/kg daily for 3 days 3

Administration Considerations

Timing and Food Interactions

• Azithromycin can be taken with or without food 1
• Avoid concurrent administration with aluminum or magnesium-containing antacids, as absorption may be reduced 3
• Dispense medication on-site when possible to improve adherence 3
• Consider directly observed first dose, particularly for single-dose STI regimens 3

Special Populations

• Renal insufficiency (GFR ≤80 mL/min): No dosage adjustment required 1
• Severe renal impairment (GFR <10 mL/min): Exercise caution; AUC increases 35% 1
• Hepatic insufficiency: No established dosage adjustments available 1
• Pregnancy: FDA Category B; single 1-gram dose is an alternative for chlamydial infections in pregnancy 3

Critical Safety Monitoring

Cardiac Considerations

• Obtain baseline ECG in patients with cardiac risk factors before initiating therapy 2, 5
• Contraindicated if QTc >450 ms (men) or >470 ms (women) 2, 5
• Avoid in patients taking other QT-prolonging medications without careful risk assessment 3

Laboratory Monitoring for Long-Term Therapy

• Measure baseline liver function tests 3
• Monitor for development of antimicrobial resistance 3

Common Pitfalls and Caveats

Resistance Concerns

• Azithromycin's long half-life (68 hours) creates a prolonged "window" of subinhibitory concentrations (14-20 days for complete elimination), potentially selecting for resistant organisms 4
• Macrolide resistance varies geographically and temporally, particularly for group A streptococcus 5
• NOT recommended as first-line for strep pharyngitis; use only in penicillin-allergic patients 5
• Long-term use increases antimicrobial resistance risk 3

Clinical Effectiveness Issues

• Some patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to azithromycin therapy 6
• Azithromycin results in more recurrence of streptococcal pharyngitis/tonsillitis compared to penicillin, necessitating the higher 12 mg/kg/day dose in children 7
• Assess clinical response at days 5-7; improvement of symptoms should be evident 2

Adverse Effects

• Common gastrointestinal effects include nausea, vomiting, abdominal pain, and diarrhea (generally mild to moderate) 3, 2
• Better GI tolerance than erythromycin 8, 6
• Incident or worsening nausea/vomiting occurs in approximately 3% of patients with GI infections 2
• Possible myopathy with long-term use 4

STI-Specific Considerations

• Patients treated for STIs should abstain from sexual intercourse for 7 days after completing therapy 3
• The single-dose advantage is particularly important in populations unlikely to return for follow-up 3

Pediatric-Specific Concerns

• Safety of re-dosing after vomiting within 30 minutes of the 30 mg/kg single dose has not been established 1
• Azithromycin is preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 3

Pharmacodynamic Principles

• Azithromycin exhibits time-dependent killing with moderate to prolonged persistent effects 4
• The pharmacodynamic parameter correlating with efficacy is the AUC:MIC ratio (target approximately 25), rather than time above MIC 4
• Extensive tissue distribution and intracellular accumulation result in tissue concentrations exceeding serum levels 8, 6
• Low serum concentrations may allow breakthrough bacteremia in severely ill patients 6