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 regimens being 500 mg on day 1 followed by 250 mg daily for days 2-5 (total 1.5g over 5 days) for respiratory infections, or a single 1-gram dose for sexually transmitted infections like chlamydia. 1

Adult Dosing by Indication

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
• Total treatment duration: 5 days
• This is the standard "Z-pack" regimen 2

Acute Bacterial Exacerbations of COPD:

• Option 1: 500 mg once daily for 3 days 1
• Option 2: 500 mg on day 1, then 250 mg daily on days 2-5 1
• Both regimens deliver 1.5g total dose

Acute Bacterial Sinusitis:

• 500 mg once daily for 3 days 1
• Alternative: 500 mg on day 1, then 250 mg daily for days 2-5 3

Pharyngitis/Tonsillitis (second-line therapy):

• 500 mg on day 1, then 250 mg daily on days 2-5 1
• Important caveat: Not first-line for strep pharyngitis due to macrolide resistance concerns 4

Sexually Transmitted Infections

Non-gonococcal Urethritis and Cervicitis (Chlamydia):

• Single 1-gram dose orally 1, 2
• This provides therapeutic tissue concentrations for approximately 10 days due to azithromycin's prolonged tissue half-life 2
• Directly observed therapy is recommended to maximize compliance 2
• Patients must abstain from sexual intercourse for 7 days after treatment 2

Gonococcal Urethritis and Cervicitis:

• Single 2-gram dose 1
• Note: This is no longer recommended as monotherapy due to resistance; current guidelines favor ceftriaxone-based regimens

Genital Ulcer Disease (Chancroid):

• Single 1-gram dose 1

Skin and Soft Tissue Infections

Uncomplicated Skin/Skin Structure Infections:

• 500 mg on day 1, followed by 250 mg once daily on days 2-5 1
• Duration approximately 7 days depending on clinical response 5

Specialized Infections

Cat Scratch Disease:

• 500 mg on day 1, followed by 250 mg daily for 4 additional days (patients >45 kg) 2
• Pediatric (<45 kg): 10 mg/kg on day 1, then 5 mg/kg for 4 more days 2

Disseminated MAC Disease (AIDS patients):

• 250 mg daily with ethambutol, with or without rifabutin 2
• For prophylaxis in AIDS patients with CD4 <50 cells/μL: 1,200 mg once weekly 2

Legionnaires' Disease:

• Hospitalized: 500 mg IV daily for 2-7 days, then oral to complete 7-10 days total 4
• Non-hospitalized (mild): 500 mg on day 1, then 250 mg daily for 4 additional days 4

Travelers' Diarrhea with Dysentery:

• Single 1-gram dose or 500 mg daily for 3 days 3

Pediatric Dosing (≥6 months)

Acute Otitis Media

Three dosing options available: 1

1. Single-dose regimen: 30 mg/kg as a single dose (maximum 1500 mg)
2. 3-day regimen: 10 mg/kg once daily for 3 days
3. 5-day regimen: 10 mg/kg on day 1, then 5 mg/kg daily on days 2-5

Community-Acquired Pneumonia

• 10 mg/kg on day 1, followed by 5 mg/kg daily on days 2-5 1
• For atypical pathogens (Mycoplasma, Chlamydophila): Same dosing 4

Acute Bacterial Sinusitis

• 10 mg/kg once daily for 3 days 1

Pharyngitis/Tonsillitis (age ≥2 years)

• 12 mg/kg once daily for 5 days (maximum 500 mg/day) 1

Pertussis

• Infants <6 months: 10 mg/kg per day for 5 days 2
• Infants and children ≥6 months: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg per day (max 250 mg) on days 2-5 2
• Preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis 2

Chlamydial Conjunctivitis (Neonates)

• 20 mg/kg per day orally once daily for 3 days 2

Administration Considerations

Timing with Food:

• Can be taken with or without food 1
• However, taking with a large meal may reduce absorption by up to 50% 6

Antacid Interactions:

• If taken with aluminum or magnesium-containing antacids, absorption may be reduced 2
• Separate administration by at least 2 hours

Directly Observed Therapy:

• Recommended for first dose, especially in STI treatment, to maximize compliance 2
• Dispense medication on-site when possible 2

Cardiac Safety Monitoring

Before initiating therapy in patients with cardiac risk factors, obtain a baseline ECG to assess QTc interval 3, 4:

• Avoid azithromycin if QTc >450 ms (men) or >470 ms (women) 3, 4
• Risk factors include: history of arrhythmias, electrolyte abnormalities, concurrent QT-prolonging medications, structural heart disease

Special Populations

Renal Insufficiency:

• No dosage adjustment needed for GFR 10-80 mL/min 1
• Caution in severe renal impairment (GFR <10 mL/min): AUC increases 35%; use with caution 1

Hepatic Insufficiency:

• Pharmacokinetics not established; no specific dose adjustment recommendations available 1
• Use with caution as metabolism is predominantly hepatic 6

Pregnancy:

• FDA Pregnancy Category B 2
• Single 1-gram dose is an alternative regimen for chlamydial infections in pregnancy 2

Age and Gender:

• No dosage adjustment based on age or gender 1

Common Side Effects

Gastrointestinal (most common): 2, 3

• Nausea, vomiting, abdominal pain, diarrhea
• Incidence approximately 3% in gastrointestinal infections 3
• Better GI tolerance than erythromycin 6, 7
• Headache and dizziness also reported 2

Pharmacodynamic Principles

Azithromycin exhibits time-dependent killing with moderate to prolonged persistent effects 5:

• The pharmacodynamic parameter correlating with efficacy is the AUC/MIC ratio rather than time above MIC 5
• Target AUC/MIC ratio is approximately 25 for maximal efficacy 5
• Terminal elimination half-life up to 68 hours 5, 6
• Tissue concentrations remain above MIC for several days after dosing, enabling short-course therapy 7

Resistance Concerns:

• The prolonged half-life creates an extended "window" of subinhibitory concentrations (14-20 days for complete elimination) 5
• This may promote selection of resistant organisms, particularly macrolide-resistant S. pneumoniae 5
• Macrolide resistance varies geographically and temporally 4

Antimicrobial Stewardship Principles

Limit antibiotic exposure whenever possible 3, 4:

• Consider viral etiology of many respiratory infections before prescribing 3
• Use the shortest effective duration to minimize resistance development 3
• Assess clinical response at days 5-7; improvement of symptoms indicates adequate therapy 3
• Not recommended as first-line for strep pharyngitis due to resistance concerns 4

Clinical Pearls

• Single-dose regimens have the advantage of improved compliance and directly observed therapy 2
• Low serum concentrations (0.4 mcg/mL after 500 mg) are offset by extensive tissue distribution (volume of distribution 23 L/kg) and intracellular accumulation 6, 8
• Tissue concentrations exceed serum concentrations and are more important for efficacy in respiratory and other infections 8
• Rapid penetration into phagocytic cells with release at local infection sites 7
• Re-dosing safety not established in pediatric patients who vomit within 30 minutes of a 30 mg/kg single dose 1