PEM Pearls: 5 Tips to Demystify Amoxicillin in Pediatric Infections

Amoxicillin is a penicillin derivative antibiotic against susceptible gram positive and gram negative bacteria. It has reasonable coverage for most upper respiratory infections and is used as prophylaxis for asplenia and bacterial endocarditis. This post aims to demystify amoxicillin treatment for common pediatric infections.

Susceptible Bacteria

Amoxicillin dosing recommendations and tips

1. Indications for high dose amoxicillin

S. pneumoniae have intermediate to high resistance to penicillin antibiotics. “High-dose” amoxicillin helps overcome this resistance, and should be used in infections commonly seen with S. pneumoniae including the 3 following conditions:

* Controversy exists regarding BID or TID dosing for the treatment of community-acquired pneumonia. A theoretical computer modeling simulation suggests that TID dosing may be superior (hypothesized 90% vs 65% cure rate for TID compared to BID dosing based on pharmacokinetics).^​1​ No randomized controlled in vivo studies on high-dose amoxicillin exist comparing the 2 dosing regimens. UpToDate recommends BID or TID with the following statement: “Although there are prospective, comparative data supporting the efficacy of twice daily dosing of amoxicillin for the treatment of acute otitis media, similar data are not available for documented pneumococcal pneumonia in children. Unless the etiologic agent is identified as a S. pneumoniae isolate with a minimum inhibitory concentration (MIC) of <2 mcg/mL, dividing the total daily 90 to 100 mg/kg dose of amoxicillin into three doses may be warranted.” The 2011 IDSA guidelines recommend 90 mg/kg/day divided in 2 doses daily or 45 mg/kg/day divided 3 doses daily.^​2​ That said, the 2018 American Academy of Pediatrics (AAP) Red Book recommends: “Oral amoxicillin at a dose of 45 mg/kg/day or 90 mg/kg/day in 3 equally divided portions is likely to be effective in ambulatory children with pneumonia caused by susceptible and relatively resistant pneumococci (MICs of 2.0 μg/mL), respectively.” And the 2017 AAP Section on Emergency Medicine’s Committee CAP Algorithm recommends TID, but states that BID is a reasonable alternative, based on local resistance patterns and MIC’s.

• Recommended max dose for suspension: 1000 mg/dose twice daily (max 2000 mg/day)
• Recommended max dose for tablet: 875 or 1000 mg/dose
• Liquid amoxicillin is available in many concentrations. Prescribe higher concentrations to minimize volumes. A common concentration is 400 mg/5 mL.

For more information on recommendations regarding observation, surveillance, and safety-net antibiotic prescription: American Academy of Pediatrics’ AOM management guidelines

2. Indications to prescribe amoxicillin-clavulanate instead of amoxicillin alone

Amoxicillin-clavulanate (Augmentin) is the antibiotic of choice when AOM treatment fails or recurs despite amoxicillin. The clavulanate irreversibly inhibits bacterial beta-lactamase, increasing the effectiveness of amoxicillin. The amoxicillin component remains “high”-dose (80-90 mg/kg/day).^​3​

Indications for prescribing amoxicillin-clavulanate include:

1. AOM treated with amoxicillin within the last 30 days: The risk of beta-lactamase resistance or of AOM due to non-typeable Haemophilus influenza and Moraxella catarrhalis (which produce beta-lactamase) increases.
2. Recurrent AOM: This is defined as having ≥3 episodes of AOM in a period of 6 months, or ≥4 episodes in 12 months.^​4​ Non-typeable Haemophilus influenza is common in recurrent episodes.
3. AOM with concomitant purulent conjunctivitis: Typically seen with non-typeable Haemophilus influenza

Amoxicillin-clavulanate prescribing:

• Amoxicillin-clavulanate dose: 80-90 mg/kg/day, divided into 2 doses daily
• Duration:
  • < 2 years of age = 10 days
  • ≥ 2 years of age = 5-7 days

3. Treatment for strep pharyngitis

A serious sequelae of strep pharyngitis is rheumatic heart disease. Children diagnosed or suspected of strep pharyngitis are treated with amoxicillin to prevent such a complication.

Traditionally, amoxicillin dosing for group A strep pharyngitis was twice daily dosing. However, recent evidence favors once daily amoxicillin in patients aged 3 years and older.^​​5​

• Amoxicillin dose: 50 mg/kg once daily (max 1000 mg/dose/day) for age ≥3 years
• Duration: 10 days

4. Treatment for pediatric community-acquired pneumonia

The etiology of pediatric community-acquired pneumonia (CAP) varies depending on age group.

The first line treatment is with high-dose amoxicillin for 7 days. If the patient does not improve 48 hours after initiating amoxicillin, consider broadening coverage to include atypical pneumonia, penicillin-resistant S. pneumo, or S. aureus. Replace amoxicillin with a macrolide, such as azithromycin.

• Azithromycin dosing: 10 mg/kg/dose PO on day 1 (max 500 mg/dose), then 5 mg/kg/dose PO daily on days 2-5 (max 250 mg/dose)
• Duration: 5 days

Also consider other etiologies, such as:

• Viral pneumonia
• Aspiration pneumonia
• Asthma
• Foreign body aspiration
• Complications of pneumonia (pleural effusion, empyema, and necrotizing pneumonia)

5. Prophylaxis treatment for bacterial infections

Amoxicillin is used as prophylaxis against bacterial infections in higher risk children. Examples include:

• Cardiac prophylaxis for a child with prosthetic heart valves, congenital heart disease, or history of previous infective endocarditis
• Urinary tract infection prophylaxis for children >2 months of age with hydronephrosis or vesiculoureteral reflux
• Prophylaxis for children with functional (e.g. secondary to sickle cell disease) or anatomic (e.g. spleen removal) asplenia

Consult a specialist for dosing and duration as needed.

Adverse Effects with Rashes

Amoxicillin is notorious for causing rashes. Amoxicillin can be continued to be used in patients with low-risk reactions, such as a rash caused by concurrent infectious mononucleosis, or by delayed-hypersensitivity reactions without features of immediate allergy. If the rash is caused by an immediate IgE-mediated reaction, penicillins should be avoided. If there is any question about whether the history or exam have features of an immediate allergy, it is recommended that the family avoid penicillins until they can be seen by an allergy specialist.

Low-risk factors that are reassuring against immediate hypersensitivity response are:

• Skin-only manifestations (without mucous membrane or systemic symptoms)
• Maculopapular rash rather than urticarial rash
• A rash that occurred days into antibiotic course
• Did not require systemic steroids to control symptoms

1. Concurrent infectious mononucleosis infection

Patients with infectious mononucleosis secondary to Epstein-Barr virus who take amoxicillin frequently develop an itchy, erythematous rash on extensor surfaces and pressure points. The rash usually resolves in 1-2 weeks after discontinuation of amoxicillin. This amoxicillin-associated rash in infectious mononucleosis is NOT thought to be a true drug allergy although its mechanism is not well understood.

2. Delayed hypersensitivity reaction

Patients may develop a rash after more than one dose of amoxicillin, or even several hours after the last dose. Patients with a “delayed” hypersensitivity reaction do NOT carry the risk of life-threatening anaphylaxis (not IgE-mediated). However, If there is a question of a severe penicillin allergy, referral to an allergy specialist for supervised re-exposure is the best course of action.

For non-severe allergy (i.e. non-anaphylactic) to penicillins, cefdinir is recommended for AOM and CAP.

• Cefdinir dose: 7 mg/kg/dose PO BID (max 600 mg/day)
• Duration: Same as for amoxicillin

3. Immediate IgE-mediated reaction

Patients with an “immediate” IgE-mediated hypersensitivity reaction to amoxicillin are at risk of developing life-threatening anaphylaxis with re-exposure. Patients may not develop symptoms with the first dose (as allergic sensitization develops), but may show symptoms within an hour of the last dose.

If the patient had a severe allergy concerning for anaphylaxis, azithromycin is recommended over a beta-lactam antibiotic for both AOM and CAP.

• Azithromycin dose: 10 mg/kg/dose PO on day 1 (max 500 mg/dose), then 5 mg/kg/dose PO daily on days 2-5 (max 250 mg/dose)
• Duration: 5 days

Take-Home Points

Amoxicillin is used to treat a variety of conditions in pediatrics, most commonly community-acquired pneumonia, acute otitis media, and streptococcal pharyngitis.

• CAP and AOM: High-dose amoxicillin (to overcome bacterial resistance) is prescribed 80-90 mg/kg/day divided into 2 doses
• Group A Strep pharyngitis: 50 mg/kg/day, once a day (to prevent rheumatic fever)
• Amoxicillin-clavulanate: Use if AOM treated in last 30 days, AOM with purulent conjunctivitis, 3+ episodes of AOM in 6 months, or 4+ episodes of AOM in 12 months
• Counseling: Educate parents/guardians on potential adverse effects with amoxicillin:
  • Rashes (due to IgE-mediated or delayed hypersensitivity reactions or to Ebstein-Barr virus co-infection)
  • If any signs of anaphylaxis, take to an ED immediately.

Thumbnail Image: © Nicholas Larento, #19510647

*Updated September 5, 2019

References

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