Many patients do not receive cephalosporins due to their penicillin allergy; most of these patients will not have an allergic response and can receive these drugs safely.

Penicillin is a commonly used antibiotic in pediatrics. The penicillins consist of a β-lactam ring and a side chain. The β-lactam ring provides the antimicrobial activity by inhibiting the bacterial penicillin-binding proteins. The side chains determine the spectrum of activity. Penicillin is often prescribed for common childhood infections, such as otitis media and sinusitis. Approximately 1% to 10% of patients who take β-lactam antibiotics report adverse reactions. These reactions are often assumed to be allergic reactions that limit their future use.

Adverse reactions can include a wide spectrum of symptoms: nausea, emesis, diarrhea, rash, or anaphylaxis. Many of these are nonimmunologic effects. It is important to elicit the details of the symptoms to differentiate between side effects and a true immunoglobulin (Ig)E-mediated reaction. Type I allergic reactions are IgE-mediated and present with signs ranging from urticaria to anaphylaxis. They typically occur from 1 to 72 hours after ingestion of the medication. Skin testing can be performed to confirm IgE-mediated reactions and is approximately 60% predictive of a reaction. Type II (IgG), III (IgG or IgM-mediated), and IV reactions to penicillin do occur, but these are not allergic (IgE-mediated) reactions.