What is a penicillin allergy cross-reaction with cephalosporins?

Patients with a documented penicillin allergy have approximately a 1 to 2 percent risk of cross-reacting with cephalosporins, much lower than the historically cited 10 percent. The cross-reactivity risk is highest with first-generation cephalosporins that share similar side chains with penicillin and lowest with third, fourth, and fifth-generation agents. Many reported penicillin allergies are not true immunoglobulin E-mediated allergies, and penicillin skin testing can confirm or rule out true allergy.