What is the appropriate treatment and dosage of azithromycin for a patient with a suspected bacterial infection, assuming no allergy to macrolide antibiotics and no underlying medical conditions?

Azithromycin Treatment and Dosing

Standard Adult Dosing Regimens

For most common bacterial infections in adults without underlying conditions, azithromycin should be administered as either 500 mg once daily for 3 days OR 500 mg on day 1 followed by 250 mg once daily on days 2-5. 1

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
• Acute bacterial exacerbations of COPD: Either 500 mg once daily for 3 days OR the 5-day regimen above 1
• Acute bacterial sinusitis: 500 mg once daily for 3 days 1
• Pharyngitis/tonsillitis: 500 mg on day 1, then 250 mg daily for days 2-5 (second-line therapy only) 1

Important Caveats for Respiratory Infections

• Azithromycin is most appropriate for suspected atypical pathogens (Mycoplasma pneumoniae, Chlamydia pneumoniae) in adults under 40 years without underlying disease 2
• For suspected pneumococcal pneumonia, particularly in adults over 40 years, amoxicillin 3 g/day is preferred over macrolides 2
• Oral azithromycin may not be adequate for pneumococcal bacteremia—breakthrough bacteremia can occur due to low serum concentrations despite adequate tissue levels 3

Sexually Transmitted Infections

• Non-gonococcal urethritis/cervicitis (Chlamydia trachomatis): Single 1-gram dose 4, 1
• Gonococcal urethritis/cervicitis: Single 2-gram dose, but must be combined with ceftriaxone 1 g IM/IV—never use as monotherapy due to resistance 4, 1
• Chancroid (genital ulcer disease): Single 1-gram dose 1

Pediatric Dosing

Standard Regimens for Children

• Acute otitis media: Either 30 mg/kg as a single dose OR 10 mg/kg once daily for 3 days OR 10 mg/kg on day 1 followed by 5 mg/kg/day on days 2-5 1
• Community-acquired pneumonia: 10 mg/kg on day 1, then 5 mg/kg once 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 (higher dose required due to increased recurrence rates with standard dosing) 1, 5

Pediatric Contraindications

• Do not use in pediatric pneumonia patients with: cystic fibrosis, nosocomial infections, known/suspected bacteremia, hospitalization requirements, or immunodeficiency/functional asplenia 1
• Infants <1 month: Use 10 mg/kg daily for 5 days for pertussis, with monitoring for infantile hypertrophic pyloric stenosis 4

Critical Safety Considerations

Cardiac Screening

• Perform ECG before initiating therapy in patients with cardiac risk factors 6
• Contraindicate if QTc >450 ms (men) or >470 ms (women) 4
• Azithromycin causes dose-dependent QT prolongation, particularly when combined with other QT-prolonging agents 2
• Avoid combination with hydroxychloroquine, certain TKIs, arsenic trioxide, and antidepressants due to additive QT prolongation risk 2

Drug Interactions

• Avoid aluminum/magnesium antacids—they reduce azithromycin absorption when taken simultaneously 4
• Monitor cyclosporine levels closely in immunocompromised patients, as azithromycin inhibits P-glycoprotein and increases cyclosporine concentrations 2
• Unlike erythromycin, azithromycin has minimal cytochrome P450 interactions and does not interact with theophylline, terfenadine, or cimetidine 7

Resistance Considerations

• Never use azithromycin monotherapy for mycobacterial infections—this applies to both M. abscessus complex and M. avium complex 2
• Macrolide resistance rates among Group A Streptococcus in the United States are approximately 5-8%; susceptibility testing should be performed 2
• Discontinue chronic azithromycin therapy during NTM evaluation—monotherapy may lead to resistance 2

Special Populations

Renal Impairment

• No dosage adjustment needed for GFR 10-80 mL/min 1
• Exercise caution with GFR <10 mL/min (AUC increases 35%) 1

Hepatic Impairment

• Pharmacokinetics not established; no specific dosage recommendations available 1

Chronic Maintenance Therapy

• Bronchiectasis with ≥3 exacerbations/year: 500 mg three times weekly or 250 mg daily for minimum 6-12 months 4
• Cystic fibrosis with chronic Pseudomonas: 250 mg daily or 250-500 mg three times weekly, continue long-term if beneficial 4
• Severe uncontrolled asthma: Trial of 500 mg three times weekly or 250 mg daily for 6-12 months, discontinue if no benefit 4

Common Pitfalls to Avoid

• Do not use for acute bronchitis in healthy adults—antibiotics are not indicated as the disease is typically viral and self-limited 2
• Do not rely on azithromycin to treat or exclude syphilis—all patients with STIs require serologic testing for syphilis 1
• Do not use for streptococcal pharyngitis as first-line therapy—penicillin remains the drug of choice for rheumatic fever prevention 2, 1
• Gastrointestinal adverse effects occur in approximately 3% of patients but are generally milder than with erythromycin 6, 5