What are the recommended macrolides (macrolide antibiotics) and their dosages for treating infections?

Macrolide Antibiotics: Recommended Agents and Dosing

Azithromycin is the preferred macrolide for most infections due to superior tolerability, convenient dosing, fewer drug interactions, and better activity against Haemophilus influenzae and Moraxella catarrhalis compared to erythromycin. 1, 2, 3

Primary Macrolide Agents and Their Optimal Uses

Azithromycin - First-Line Choice

Azithromycin should be selected over other macrolides for most respiratory and sexually transmitted infections due to its once-daily dosing, excellent tissue penetration, and minimal drug-drug interactions. 1, 2, 3

Standard Adult Dosing Regimens:

• Community-acquired pneumonia/respiratory infections: 500 mg on day 1, then 250 mg daily on days 2-5 (standard Z-pack) 1
• Chlamydial infections (urethritis/cervicitis): Single 1 gram dose orally, providing therapeutic concentrations for approximately 10 days 1
• Bronchiectasis with ≥3 exacerbations/year: 500 mg three times weekly (strongest evidence) OR 250 mg daily 4, 1
• COPD with frequent exacerbations: 250 mg three times weekly (lower dose to minimize side effects) OR 500 mg three times weekly 4
• Cat scratch disease (>45 kg): 500 mg on day 1, then 250 mg daily for 4 additional days 1
• Disseminated MAC in AIDS: 250 mg daily with ethambutol, with or without rifabutin 1
• MAC prophylaxis in AIDS (CD4 <50): 1,200 mg once weekly 1

Pediatric Dosing:

• Pertussis (<6 months): 10 mg/kg daily for 5 days 1
• Pertussis (≥6 months): 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg daily (max 250 mg) on days 2-5 1
• Cat scratch disease (<45 kg): 10 mg/kg on day 1, then 5 mg/kg daily for 4 additional days 1
• Chlamydial conjunctivitis in neonates: 20 mg/kg daily for 3 days 1

Clarithromycin - Alternative Agent

Clarithromycin should be reserved for specific indications including active MAC disease (most potent MAC activity), Helicobacter pylori eradication, and patients requiring twice-daily dosing. 5, 2, 3

Standard Adult Dosing:

• Respiratory tract infections: 500 mg twice daily 5
• Elderly or low body weight patients: 250 mg twice daily to minimize toxicity 5
• MAC treatment (most active agent): Part of multidrug regimen 3
• Primary immunodeficiency prophylaxis: 500 mg daily or twice daily 5

Pediatric Dosing:

• Weight-based: 7.5 mg/kg twice daily (max 500 mg per dose) 5
• IV infusion (1 month to 11 years): 7.5 mg/kg twice daily (max 500 mg) 5

Renal Dosing Adjustments:

• Moderate impairment: No adjustment unless toxicity develops 5
• Severe impairment: Reduce dose by 50% 5

Erythromycin - Limited Current Role

Erythromycin should only be used when azithromycin and clarithromycin are contraindicated, as it has inferior tolerability, more drug interactions, and requires four-times-daily dosing. 6, 2, 3

Specific Indications Where Still Used:

• Erythromycin ethylsuccinate for bronchiectasis: 400 mg twice daily (based on Australian RCT data) 4
• Early Lyme disease (if intolerant of first-line agents): 500 mg four times daily for 14-21 days 4

Critical Safety Monitoring for Long-Term Macrolide Therapy

Pre-Treatment Requirements:

Before initiating any long-term macrolide therapy, obtain an ECG to assess QTc interval—therapy is contraindicated if QTc >450 ms (men) or >470 ms (women). 4, 1, 5

• Baseline ECG mandatory: Check QTc interval before starting 4, 1, 5
• Baseline liver function tests: Required for long-term therapy 4, 1
• Baseline audiometry: Recommended, especially for clarithromycin 5
• Drug interaction screening: Avoid concurrent QT-prolonging medications 4, 1
• Cardiac history assessment: Exclude heart disease, slow pulse, family history of sudden death, previous low potassium 4

During Treatment Monitoring:

• Repeat ECG at 1 month: Stop if new QTc prolongation develops 4, 5
• Liver function tests: Check at 1 month, then every 6 months 4
• Clinical benefit assessment: Evaluate at 6 and 12 months using objective measures (exacerbation rate, quality of life scores)—stop if no benefit 4
• Audiometry if symptoms develop: Particularly with clarithromycin 5

Microbiological Considerations:

Perform sputum microbiological assessment before starting long-term macrolides, including investigation for nontuberculous mycobacteria (NTM)—avoid macrolide monotherapy if NTM identified. 4

• Pre-treatment sputum culture: Essential to exclude NTM and assess baseline pathogens 4
• Repeat cultures with clinical decline: Monitor for resistance patterns during exacerbations 4
• Antimicrobial resistance risk: Long-term use increases resistance, though clinical impact uncertain 4

Common Pitfalls and How to Avoid Them

Dosing Strategy for Bronchiectasis:

Start azithromycin at 500 mg three times weekly (or 250 mg daily) for bronchiectasis, as this has the strongest RCT evidence for reducing exacerbations, but consider starting at 250 mg three times weekly in patients with history of drug intolerances. 4

The British Thoracic Society acknowledges that while side effects are common, study dropouts are rare, and the strongest efficacy evidence supports higher dosing regimens. 4 If gastrointestinal side effects occur at 500 mg three times weekly, dose reduction to 250 mg three times weekly can be considered if clinical benefit has been demonstrated. 4

Drug Interaction Hierarchy:

Azithromycin has minimal drug-drug interactions (Group 3), clarithromycin has moderate interactions (Group 2), and erythromycin has frequent interactions (Group 1)—this should guide agent selection in polypharmacy patients. 7

• Erythromycin: Significant interactions with theophylline, carbamazepine, warfarin, cyclosporine, terfenadine, digoxin 6
• Clarithromycin: Moderate interaction potential, avoid with calcium channel blockers in elderly (acute kidney injury risk) 8
• Azithromycin: Minimal interactions, preferred in complex medication regimens 2, 7

Macrolide Selection for Specific Pathogens:

For infections involving H. influenzae or M. catarrhalis, choose azithromycin or clarithromycin—never erythromycin—due to superior activity. 2, 3

• Community-acquired pneumonia: Azithromycin or clarithromycin preferred over erythromycin 2, 3
• Helicobacter pylori: Clarithromycin is the macrolide of choice 2
• Chlamydia trachomatis: Azithromycin preferred (single 1 gram dose) 2
• MAC treatment: Clarithromycin most active, must be part of regimen 3
• MAC prophylaxis: Azithromycin preferred due to fewer drug interactions 3

Limitations as Monotherapy:

Never use macrolides as monotherapy for gonorrhea due to widespread resistance—always combine with ceftriaxone if gonococcal infection suspected. 1

Macrolides are less effective than doxycycline or beta-lactams for early Lyme disease and should only be used when first-line agents are contraindicated, with close observation for treatment failure. 4

Gastrointestinal Tolerability:

Azithromycin and clarithromycin cause significantly less gastrointestinal distress than erythromycin, improving compliance and reducing treatment discontinuation. 6, 3

• Common side effects: Nausea, vomiting, abdominal pain, diarrhea (less frequent with newer macrolides) 1, 6
• Clarithromycin-specific: Metallic taste, dose-dependent toxicity (most adults cannot tolerate >1,000 mg/day) 5
• Management strategy: Dose reduction may ameliorate symptoms but may reduce efficacy 4

Duration of Therapy Considerations:

For bronchiectasis and COPD, long-term macrolides require minimum 6 months of therapy to demonstrate benefit in reducing exacerbations, with optimal duration up to 12 months. 4

Evidence shows exacerbation reduction persists for 6 months after stopping a 6-month course, though impact of restarting therapy is unknown. 4 Studies beyond 12 months are lacking, so longer-term benefits and risks remain unestablished. 4

Special Population Considerations:

Azithromycin is preferred over erythromycin in infants <1 month due to lower risk of infantile hypertrophic pyloric stenosis. 1

In pregnancy, azithromycin is FDA Category B and can be used as a single 1 gram dose for chlamydial infections. 1, 8

Elderly patients are more susceptible to torsades de pointes and acute kidney injury with clarithromycin (especially when combined with calcium channel blockers), requiring heightened monitoring. 8