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 for days 2-5 (total 1.5 g), though sexually transmitted infections typically require a single 1 gram dose, and pediatric dosing is weight-based at 10 mg/kg on day 1 then 5 mg/kg daily for 4 days. 1

Adult Dosing Regimens

Respiratory Tract Infections

• Community-acquired pneumonia (mild): 500 mg on day 1, then 250 mg once daily on days 2-5 1
• Acute bacterial exacerbations of COPD: Either 500 mg daily for 3 days OR 500 mg on day 1 followed by 250 mg daily on days 2-5 1
• Acute bacterial sinusitis: 500 mg daily for 3 days 1
• Pharyngitis/tonsillitis (second-line): 500 mg on day 1, then 250 mg daily on days 2-5 1
• Atypical pneumonia (Mycoplasma, Chlamydia, Coxiella): Either 500 mg daily for 3 days OR the standard 5-day regimen, both equally effective 2

Sexually Transmitted Infections

• Non-gonococcal urethritis/cervicitis (Chlamydia): Single 1 gram dose 1, 3
• Gonococcal urethritis/cervicitis: Single 2 gram dose 1
• Chancroid: Single 1 gram dose 1

The single-dose regimen for chlamydial infections provides therapeutic tissue concentrations for approximately 10 days due to azithromycin's prolonged tissue half-life, with the major advantage being improved compliance through directly observed therapy 3.

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

Specialized Indications

• 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 days 5
• Disseminated MAC in AIDS: 250 mg daily with ethambutol ± rifabutin 3
• MAC prophylaxis in AIDS (CD4 <50): 1,200 mg once weekly 3
• Travelers' diarrhea with dysentery: Single 1 gram dose or 500 mg daily for 3 days 6

Pediatric Dosing Regimens

Standard Weight-Based Dosing

The most common pediatric regimen is 10 mg/kg (maximum 500 mg) on day 1, followed by 5 mg/kg (maximum 250 mg) daily on days 2-5. 1, 7

Acute Otitis Media (≥6 months)

Three options available 1:

• 5-day regimen: 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5
• 3-day regimen: 10 mg/kg daily for 3 days
• Single-dose regimen: 30 mg/kg as a single dose

Acute Bacterial Sinusitis (≥6 months)

• 3-day regimen: 10 mg/kg daily for 3 days 1

Community-Acquired Pneumonia (≥6 months)

• 5-day regimen: 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 1, 5

Pharyngitis/Tonsillitis (≥2 years)

• 12 mg/kg once daily for 5 days (higher dose required due to higher recurrence rates with standard dosing) 1, 7

Pertussis

• Infants <6 months: 10 mg/kg daily for 5 days 3
• Infants/children ≥6 months: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) daily on days 2-5 3

Chlamydial Conjunctivitis (Neonates)

• 20 mg/kg daily for 3 days 3

Cat Scratch Disease (<45 kg)

• 10 mg/kg on day 1, then 5 mg/kg daily for 4 additional days 3

Administration Considerations

Timing and Food

• Can be taken with or without food 1
• Avoid coadministration with aluminum or magnesium-containing antacids, as absorption may be reduced 3
• A large meal may reduce absorption by up to 50% 8

Cardiac Monitoring

Before initiating azithromycin in patients with cardiac risk factors, obtain a baseline ECG to assess QTc interval. 6, 5

• Avoid azithromycin if QTc >450 ms (men) or >470 ms (women) 6, 5

Special Populations

• Renal insufficiency: No dosage adjustment needed for GFR 10-80 mL/min; use caution if GFR <10 mL/min (35% increase in AUC) 1
• Hepatic insufficiency: Pharmacokinetics not established; no specific recommendations available 1
• Pregnancy: FDA Category B; single 1 gram dose is an alternative for chlamydial infections in pregnancy 3
• Infants <1 month: Azithromycin preferred over erythromycin due to lower risk of infantile hypertrophic pyloric stenosis 3

Common Pitfalls and Caveats

Resistance Concerns

Azithromycin's prolonged 68-hour half-life creates an extended "window" of subinhibitory concentrations (14-20 days for complete elimination), potentially selecting for macrolide-resistant bacteria. 4

• Studies show azithromycin-resistant S. pneumoniae carriage rates increased from 2% pre-treatment to 55% at 2-3 weeks, declining to 6% by 6 months 4
• Macrolide resistance varies geographically and temporally, particularly for Group A Streptococcus 5
• Not recommended as first-line for strep pharyngitis; reserve for penicillin-allergic patients 5

Clinical Monitoring

• Assess clinical response at days 5-7; improvement of symptoms should be evident 6
• Patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to azithromycin, requiring physician vigilance 9
• Breakthrough bacteremia may occur in severely ill patients due to low serum concentrations, though tissue concentrations are more clinically relevant 9

Adverse Effects

• Common gastrointestinal effects (3% incidence): nausea, vomiting, abdominal pain, diarrhea 3, 6
• Better GI tolerance than erythromycin 8, 9
• Symptoms tend to be mild to moderate in severity 7

Antimicrobial Stewardship

• Use the shortest effective duration to minimize resistance development 6
• Consider viral etiology before prescribing for respiratory infections 6, 5
• Dispense medication on-site when possible to improve adherence 3
• For sexually transmitted infections, patients should abstain from sexual intercourse for 7 days after completing therapy 3

Pediatric-Specific Considerations

• Safety of re-dosing after vomiting within 30 minutes of the 30 mg/kg single dose has not been established, though 8 patients in clinical trials were successfully re-dosed 1
• The 3-day and 1-day regimens for community-acquired pneumonia in pediatrics have not been established for effectiveness 1
• The 5-day or 1-day regimens for acute bacterial sinusitis in pediatrics have not been established for effectiveness 1

Pharmacodynamic Principles

Azithromycin exhibits time-dependent killing with a moderate to prolonged persistent effect; the pharmacodynamic parameter correlating with efficacy is the AUC:MIC ratio (target approximately 25), not time above MIC. 4

• Extensive tissue distribution (volume of distribution 23 L/kg) with intracellular accumulation 8
• Low peak serum levels (0.4 mcg/mL after 500 mg) but high tissue concentrations exceeding those of erythromycin 8, 9
• Terminal elimination half-life up to 5 days 8