What are the recommended azithromycin (Zithromax) dosing regimens for healthy adults and children—including oral single‑dose, multi‑day courses, intravenous therapy for severe infections, and dose adjustments for renal or hepatic impairment?

Azithromycin (Zithromax) Dosing Guidelines

For most adult respiratory tract infections, prescribe azithromycin 500 mg on day 1 followed by 250 mg once daily on days 2–5 (the standard Z-pack), or alternatively 500 mg once daily for 3 consecutive days—both regimens deliver the same 1.5 gram total dose and are equally effective. 1

Standard Adult Dosing by Indication

Respiratory Tract Infections

• Community-acquired pneumonia, acute bacterial sinusitis, bronchitis: 500 mg on day 1, then 250 mg once daily on days 2–5 (total 5 days) 1
• Alternative 3-day regimen: 500 mg once daily for 3 consecutive days—provides equivalent efficacy with improved compliance 1, 2
• Severe pneumonia requiring hospitalization: 500 mg IV daily for 2–5 days, followed by oral 500 mg daily to complete 7–10 days total 3
• Atypical pneumonia (Mycoplasma, Chlamydophila): Either the 3-day or 5-day regimen is effective; most patients become afebrile within 48 hours 2

Sexually Transmitted Infections

• Non-gonococcal urethritis and cervicitis (Chlamydia trachomatis): Single 1 gram oral dose—this is the preferred regimen due to directly observed therapy and superior compliance 4, 1, 3
• Persistent non-gonococcal urethritis (after doxycycline failure): 500 mg on day 1, then 250 mg daily for 4 additional days 1, 3
• Critical caveat: Never use azithromycin as monotherapy for gonorrhea due to widespread resistance; must combine with ceftriaxone 500 mg IM if gonococcal infection is suspected 1, 3

Skin and Soft Tissue Infections

• Uncomplicated skin infections: 500 mg once daily for 3 days 5
• Clinical resolution rates of 83% with bacteriological eradication of 90% have been demonstrated 5

Enteric Fever (Typhoid)

• Adults: 500 mg once daily for 5–7 days (maximum 1 gram/day) 6
• Children: 20 mg/kg/day once daily for 5–7 days (maximum 1 gram/day) 6
• Azithromycin is positioned as second-line therapy after fluoroquinolone failure or in quinolone-resistant cases, with significantly lower relapse rates compared to ceftriaxone 6

Pediatric Dosing Regimens

Respiratory Tract Infections

• Standard 5-day regimen: 10 mg/kg (maximum 500 mg) on day 1, followed by 5 mg/kg once daily (maximum 250 mg/day) on days 2–5 1, 7, 8
• Alternative 3-day regimen: 10 mg/kg/day (maximum 500 mg) once daily for 3 consecutive days 7
• Both regimens are equally effective for otitis media, community-acquired pneumonia, and bronchitis 7

Pertussis

• Infants <6 months: 10 mg/kg per day for 5 days 1, 3
• Children ≥6 months: 10 mg/kg (maximum 500 mg) on day 1, then 5 mg/kg (maximum 250 mg) on days 2–5 1, 3

Chlamydial Conjunctivitis in Neonates

• 20 mg/kg body weight per day once daily for 3 days 3

Complicated Intra-Abdominal Infections (Pediatric)

• Dosing is not specifically detailed in the provided guidelines for azithromycin in this indication; other agents are preferred 4

Long-Term Prophylactic Therapy

Bronchiectasis (≥3 exacerbations per year)

• Preferred starting dose: 250 mg three times weekly 3
• Alternative regimens: 250 mg daily or escalate to 500 mg three times weekly based on clinical response 1, 3
• Minimum duration: At least 6 months to demonstrate benefit in exacerbation reduction 1, 3
• Monitoring: Review every 6 months for efficacy, toxicity, and continuing need; obtain baseline and periodic liver function tests 3
• Critical prerequisite: Ensure at least one negative respiratory nontuberculous mycobacteria (NTM) culture before starting long-term therapy 3

Bronchiolitis Obliterans Syndrome (Lung Transplant Recipients)

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

Administration Considerations

Timing and Food Interactions

• Azithromycin can be taken with or without food 6
• Separate from aluminum- or magnesium-containing antacids by at least 2 hours, as antacids reduce absorption by up to 50% 1, 3, 6

Compliance Optimization

• Dispense medication on-site and directly observe the first dose when possible, particularly for sexually transmitted infections in populations unlikely to return for follow-up 1, 3
• Single-dose and once-daily regimens significantly improve adherence compared to multiple-daily-dose alternatives 1, 6

Dose Adjustments for Organ Impairment

Renal Impairment

• No dose adjustment is routinely required for mild to moderate renal dysfunction 3
• Severe renal impairment (CrCl <10 mL/min): Exercise caution, as AUC increases by 35% and Cmax by 61%; consider dose reduction or increased monitoring 3
• Elderly patients: Calculate estimated GFR rather than relying on serum creatinine alone, as age-related muscle loss can mask renal impairment 3

Hepatic Impairment

• Use with caution and increase monitoring if underlying liver disease is present 3, 6
• Obtain baseline liver function tests before initiating long-term therapy 3

Critical Safety Monitoring and Precautions

Cardiac Risk Assessment

• Obtain baseline ECG in patients with cardiovascular disease, those taking other QT-prolonging medications, or patients ≥75 years old before initiating therapy 1, 3
• Contraindication: QTc >450 ms (men) or >470 ms (women) 1, 3
• Discontinue immediately if QTc exceeds 500 ms or rises >60 ms from baseline 3
• Azithromycin increases cardiovascular death risk (HR 2.88; 95% CI 1.79–4.63) in patients with high baseline cardiovascular risk 3

Drug Interactions

• Avoid concurrent use with other QT-prolonging agents (Class IA/III antiarrhythmics, certain antipsychotics, fluoroquinolones) unless cardiology consultation is obtained 3
• Azithromycin is strongly preferred over clarithromycin in older adults due to far fewer cytochrome P450-mediated interactions 3
• Unlike clarithromycin, azithromycin does not significantly interact with rifamycins, statins, or warfarin 3

Electrolyte Monitoring

• Verify and correct baseline potassium and magnesium levels before initiating therapy, as electrolyte abnormalities increase QT prolongation risk 3

Gastrointestinal Adverse Effects

• Common side effects include diarrhea, abdominal pain, nausea, and vomiting—generally mild to moderate 1, 3, 6
• Monitor for severe watery or bloody diarrhea that could indicate Clostridioides difficile infection 1

Common Pitfalls and Clinical Pearls

Inappropriate Use

• Azithromycin is NOT first-line for streptococcal pharyngitis due to increasing macrolide resistance in group A Streptococcus; use only as an alternative in penicillin-allergic patients 1
• For streptococcal pharyngitis when azithromycin is necessary, use 12 mg/kg/day for 5 days in children to reduce recurrence rates 7

Resistance Concerns

• Long-term macrolide use increases antimicrobial resistance, though the clinical impact remains uncertain 3
• Older antibiotics (chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole) are no longer recommended for enteric fever due to widespread resistance 6

Expected Clinical Response

• Most patients with respiratory tract infections experience noticeable improvement within 48 hours of therapy initiation 1, 2
• Persistence of fever beyond 48–72 hours should prompt reassessment and consideration of alternative therapy 1
• For sexually transmitted infections, patients should abstain from sexual intercourse for 7 days after completing therapy 1, 3

Special Populations

• Pregnancy: Azithromycin is FDA Pregnancy Category B and is safe; preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 1, 3
• Elderly patients (≥75 years): Women have higher baseline susceptibility to drug-induced QT prolongation; be especially vigilant with ECG monitoring 3