What is the best course of action for an 8-year-old boy with a 10-day history of cough, fevers, rhinorrhea, and otalgia, treated with amoxicillin (amoxil), who now presents with a red, flat, well-demarcated rash on his bilateral knees?

Management of Amoxicillin-Associated Rash in a Child with Viral Upper Respiratory Infection

Discontinue amoxicillin immediately, as this child most likely has a benign viral-drug interaction rash rather than a true drug allergy, and the antibiotic was inappropriately prescribed for a viral illness in the first place. 1, 2

Immediate Assessment and Action

Stop the amoxicillin now. The clinical presentation—10 days of upper respiratory symptoms (cough, fever, rhinorrhea) followed by a flat, well-demarcated rash on day 10 of illness—strongly suggests a viral exanthem occurring during concurrent amoxicillin therapy rather than a bacterial infection requiring antibiotics. 3

Key Diagnostic Considerations

• This rash pattern is consistent with a benign viral-drug interaction, NOT a true penicillin allergy. The maculopapular (flat, red) rash appearing 8-10 days into treatment falls within the typical window for delayed cutaneous reactions to aminopenicillins during viral illness. 1, 4

• The original indication for amoxicillin was likely inappropriate. Antibiotics provide no benefit for nonspecific upper respiratory infections and common colds, and prescribing them only exposes children to potential harm. 3

• Rash and diarrhea occur in approximately 5% more children treated with amoxicillin compared to placebo in clinical trials, with even higher rates when viral illness is present. 3

Distinguishing Benign Rash from True Allergy

Features Suggesting Benign Viral-Drug Interaction (This Case):

• Maculopapular (flat, red) rash appearing 7-10 days after starting amoxicillin 1, 4
• Well-demarcated, localized distribution (bilateral knees) 1
• No urticaria, angioedema, or respiratory symptoms 1, 2
• No blistering, skin exfoliation, or mucosal involvement 1, 2
• Concurrent viral upper respiratory symptoms 1, 5

Red Flags Requiring Emergency Evaluation (NOT Present Here):

• Urticaria (hives) with immediate onset within 1 hour of dosing 1, 2
• Angioedema (facial/lip swelling) or respiratory symptoms 1, 2
• Blistering, skin exfoliation, or mucosal involvement (Stevens-Johnson syndrome/toxic epidermal necrolysis) 1, 2
• Systemic symptoms with eosinophilia (DRESS syndrome) 1, 5

Management Plan

Immediate Steps:

• Discontinue amoxicillin immediately 1, 2
• Monitor the rash over the next 24-48 hours for progression or development of concerning features 1
• Provide symptomatic care with acetaminophen or ibuprofen for fever or discomfort 1
• Reassure the family that this does NOT represent a true penicillin allergy 1, 4

Critical Labeling Decision:

DO NOT label this child as "penicillin allergic" based on this rash. Over 90% of children with reported amoxicillin rashes tolerate the drug on re-exposure, and permanently labeling children as penicillin-allergic leads to unnecessary use of broader-spectrum, less effective antibiotics with increased resistance and healthcare costs. 1

Future Antibiotic Use

Amoxicillin can and should be used in the future if this child requires antibiotics for a true bacterial infection (such as confirmed acute otitis media, streptococcal pharyngitis, or bacterial pneumonia). 1, 4

When Future Bacterial Infection Occurs:

• Direct amoxicillin challenge (single dose under medical observation) is recommended when the child next requires antibiotics, typically showing 5-10% reaction rates on rechallenge that are generally no more severe than the original reaction. 1
• Penicillin skin testing has limited utility for non-IgE-mediated maculopapular rashes and should NOT be performed for this type of reaction. 1

Common Pitfalls to Avoid

• Do not continue antibiotics "to complete the course" when the original indication was inappropriate—this only increases harm without benefit. 3
• Do not switch to alternative antibiotics (such as cephalosporins or macrolides) for this viral illness, as no antibacterial therapy is indicated. 3
• Do not order allergy testing for this benign maculopapular rash, as it provides no useful information and may lead to false-positive results. 1
• Do not document a penicillin allergy in the medical record based solely on this presentation. 1, 4

Special Consideration: Infectious Mononucleosis

If this child has infectious mononucleosis (Epstein-Barr virus), 30-100% of patients develop a non-pruritic morbilliform rash when given amoxicillin, which represents a unique virus-drug interaction rather than true allergy. 1, 2 However, the FDA label specifically states that amoxicillin should not be administered to patients with known mononucleosis. 2

Expected Clinical Course

• The rash should resolve spontaneously within 2-5 days after discontinuing amoxicillin, without sequelae. 1, 4, 5
• The underlying viral illness should improve with supportive care alone over the next several days. 3
• If symptoms worsen or new concerning features develop (respiratory distress, blistering, mucosal involvement), immediate emergency evaluation is required. 1, 2