What is the proper dosing and administration of azithromycin (macrolide antibiotic) for a patient with an infection?

How to Take Azithromycin

For most common infections in adults, take azithromycin 500 mg on day 1, followed by 250 mg once daily on days 2 through 5, or alternatively 500 mg once daily for 3 days—both regimens are equally effective due to azithromycin's prolonged tissue half-life. 1

Standard Adult Dosing by Indication

Respiratory Tract Infections

• Community-acquired pneumonia (mild): 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
• Acute 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
• Pharyngitis/tonsillitis (second-line): 500 mg on day 1, then 250 mg daily on days 2-5 1

Sexually Transmitted Infections

• Non-gonococcal urethritis/cervicitis (chlamydia): Single 1 gram dose 2, 1
• Gonococcal urethritis/cervicitis: Single 2 gram dose 1
• Chancroid (genital ulcer disease): Single 1 gram dose 1

Severe or Hospitalized Infections

• Severe community-acquired pneumonia: 500 mg IV daily for 2-5 days, then switch to oral 500 mg daily to complete 7-10 days total 2
• Legionnaires' disease (hospitalized): 500 mg IV daily for 2-7 days, then oral to complete 7-10 days total 3
• Legionnaires' disease (mild, outpatient): 500 mg on day 1, then 250 mg daily for 4 additional days 3

Administration Considerations

Timing and Food

• Azithromycin tablets can be taken with or without food 1
• Taking with a large meal may reduce absorption by up to 50%, but this is generally not clinically significant for most infections 4

Antacid Interactions

• Avoid taking azithromycin simultaneously with aluminum or magnesium-containing antacids, as this reduces absorption 2
• Separate administration by at least 2 hours if antacids are necessary 2

Pediatric Dosing

Respiratory Infections

• Acute otitis media: 30 mg/kg as a single dose OR 10 mg/kg once daily for 3 days OR 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 1
• Community-acquired pneumonia: 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 1
• Acute bacterial sinusitis: 10 mg/kg once daily for 3 days 1
• Pharyngitis/tonsillitis: 12 mg/kg once daily for 5 days (ages 2 years and above) 1

Atypical Pathogens in Children

• Mycoplasma pneumoniae or Chlamydia pneumoniae: 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5 3

Critical Safety Considerations

Cardiac Monitoring

• Obtain a baseline ECG in patients with cardiac risk factors before starting azithromycin 3, 5
• Avoid azithromycin if QTc >450 ms (men) or >470 ms (women) 2, 3, 5
• A Tennessee Medicaid study showed increased cardiovascular deaths (HR 2.88) with 5-day azithromycin therapy, particularly in high-risk patients 2
• Do not use azithromycin in patients taking other QT-prolonging medications without careful risk assessment 2

Renal Impairment

• No dose adjustment needed for GFR 10-80 mL/min 1
• Use caution in severe renal impairment (GFR <10 mL/min), as AUC increases by 35% 1
• Elderly patients may have reduced renal function despite normal creatinine due to decreased muscle mass—assess using estimated GFR 2

Hepatic Impairment

• Use azithromycin with caution and increase monitoring if underlying liver disease is present 2
• No specific dose adjustment recommendations exist, as pharmacokinetics have not been established in hepatic impairment 1

Long-Term Prophylactic Regimens

Bronchiectasis with Frequent Exacerbations

• For patients with ≥3 exacerbations per year: 250 mg three times weekly OR 500 mg three times weekly OR 250 mg daily 2
• Minimum duration: At least 6 months to demonstrate benefit in exacerbation reduction 2
• Monitoring: Review every 6 months for efficacy, toxicity, and continuing need 2
• Screen for nontuberculous mycobacteria (NTM): Ensure at least one negative respiratory NTM culture before starting long-term therapy 2

Bronchiolitis Obliterans Syndrome (Lung Transplant)

• 250 mg daily for 5 days, then 250 mg three times weekly for at least 3 months 2

MAC Prophylaxis in AIDS

• 1,200 mg once weekly for MAC prophylaxis in AIDS patients with CD4 <50 cells/μL 2
• 250 mg daily with ethambutol (with or without rifabutin) for disseminated MAC disease 2

Common Pitfalls and Caveats

Resistance Considerations

• Do not use azithromycin as monotherapy for gonorrhea due to widespread resistance—combine with ceftriaxone if gonococcal infection is suspected 2
• Macrolide resistance varies geographically, particularly for group A streptococcus 3
• Azithromycin is not first-line for strep pharyngitis, but can be used as an alternative in penicillin-allergic patients 3

Compliance Advantages

• Single-dose regimens (1 gram for chlamydia) have the critical advantage of directly observed therapy, particularly important in populations unlikely to return for follow-up 2
• The 3-day regimen provides equivalent efficacy to the 5-day regimen while improving compliance 2

Tissue Concentrations vs. Serum Levels

• Azithromycin achieves low serum concentrations but very high tissue concentrations (23 L/kg volume of distribution) 4, 6
• Tissue concentrations exceed MICs for target pathogens for up to 10 days after a 5-day course 7
• This prolonged tissue half-life (68 hours) allows for short-course therapy 2

Adverse Effects

• Common side effects include nausea, diarrhea, abdominal pain, and vomiting—generally mild to moderate 2
• Gastrointestinal tolerance is better than erythromycin 4, 6
• Long-term use increases antimicrobial resistance, though clinical impact remains uncertain 2

Special Populations

• Azithromycin is FDA Pregnancy Category B and considered safe in pregnancy 2, 5
• Preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 2
• For pertussis in infants <6 months: 10 mg/kg per day for 5 days 2

When to Reassess

• Assess clinical response at days 5-7—if no improvement, consider alternative pathogens or resistance 2
• For sexually transmitted infections, patients should abstain from sexual intercourse for 7 days after completing therapy 2