What is the appropriate regimen for using amoxicillin with azithromycin for treating infections?

Amoxicillin with Azithromycin Regimen for Treating Infections

For community-acquired pneumonia (CAP), amoxicillin 90 mg/kg/day in 2 doses can be combined with azithromycin 10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2-5 for children, or azithromycin 500 mg on day 1 followed by 250 mg daily for days 2-5 for adults. 1, 2

Specific Regimens by Infection Type

Community-Acquired Pneumonia

• For children <5 years: Amoxicillin 90 mg/kg/day in 2 doses with azithromycin 10 mg/kg on day 1, followed by 5 mg/kg/day once daily for days 2-5 1
• For children ≥5 years: Amoxicillin 90 mg/kg/day in 2 doses (up to maximum 4 g/day) with azithromycin added if atypical pneumonia cannot be distinguished from bacterial pneumonia 1
• For adults: Amoxicillin with azithromycin 500 mg on day 1, followed by 250 mg daily for days 2-5 2

Sexually Transmitted Infections (Chlamydia in Pregnancy)

• Amoxicillin 500 mg orally three times a day for 7 days is recommended for pregnant women with chlamydial infections 1
• Azithromycin 1 g orally in a single dose is an alternative regimen for pregnant women 1
• Note: These medications are typically used separately, not in combination, for this indication 1

Safety Considerations

Before Starting Therapy

• Perform an ECG to assess QTc interval before initiating azithromycin, especially in patients with cardiac risk factors 2
• Avoid azithromycin if QTc is >450 ms for men and >470 ms for women 2
• Measure baseline liver function tests before starting therapy 2
• Consider drug interactions: azithromycin should not be administered concomitantly with astemizole, cisapride, pimazole, or terfenadine 1
• Caution patients not to take azithromycin and aluminum- or magnesium-containing antacids simultaneously 1

Monitoring During Treatment

• Monitor for gastrointestinal side effects, which are the most common adverse reactions (nausea, vomiting, abdominal pain, diarrhea) 1, 3
• For infants <1 month receiving macrolides, monitor for infantile hypertrophic pyloric stenosis 1
• Assess response to therapy at days 5-7 (improvement of symptoms) 2

Special Populations

Pregnant Women

• Doxycycline and fluoroquinolones are contraindicated in pregnancy 1
• Azithromycin is considered safe and effective in pregnancy 1
• Amoxicillin 500 mg three times daily for 7 days is a recommended regimen for chlamydial infections in pregnancy 1
• Erythromycin estolate is contraindicated during pregnancy due to hepatotoxicity 1

Children

• For children <1 month, azithromycin is preferred over erythromycin due to risk of infantile hypertrophic pyloric stenosis 1
• For children with CAP, dosing is weight-based: amoxicillin 90 mg/kg/day in 2 doses with azithromycin 10 mg/kg on day 1, followed by 5 mg/kg/day for days 2-5 1

Duration of Therapy

• For most respiratory infections, a 3-day course of azithromycin (500 mg daily) has shown similar efficacy to longer courses 4, 5, 6
• For CAP, a 5-day course of azithromycin (500 mg on day 1, then 250 mg daily) is commonly recommended 2
• When combined with amoxicillin for presumed bacterial pneumonia with atypical coverage, the standard duration is 5 days for azithromycin 1
• For sexually transmitted infections like chlamydia, amoxicillin is given for 7 days (500 mg three times daily) 1

Antimicrobial Stewardship Considerations

• Limit antibiotic exposure whenever possible to minimize development of resistance 2
• Consider viral etiology of many upper respiratory infections before prescribing antibiotics 2
• Use the shortest effective duration of antimicrobial therapy 2
• For CAP, if both bacterial and atypical pathogens are suspected, the combination provides coverage for both 1

Common Pitfalls and Caveats

• Macrolides like azithromycin should not be administered with certain medications that can prolong QT interval 1
• Gastrointestinal side effects are common with both medications but more frequent with erythromycin than azithromycin 1, 3
• Patients should abstain from sexual intercourse until they and their partners have completed treatment for sexually transmitted infections 1
• Treatment failure with azithromycin has been reported in patients who have had splenectomy, HIV infection, or concurrent corticosteroid therapy 1
• Short-course azithromycin (3-day regimen) has shown similar efficacy to longer courses of antibiotics for respiratory infections, which may improve compliance 4, 7, 8