Ten percent of patients who are allergic to penicillin will have serious reactions if exposed to cephalosporins

Cephalosporins and penicillins share a common betalactam ring. It is commonly taught that at least 10% of patients who are allergic to penicillin will have an adverse reaction to cephalosporins. This potential cross-reactivity has extremely important therapeutic implications because many serious infections are best treated with cephalosporins as first-line therapy.

In considering cross-reactivity, two important points must be made. First, true penicillin allergy is not common. Graff-Lonnevig et al¹ noted that in a cohort of 298 children whose parents gave the history of penicillin allergy, only one had a positive result on a radioallergosorbent test (an in vitro test of penicillin allergy). A 10-day course of antibiotics was given to the other 297 patients. Only 10% of children had any reaction that was consistent with allergy, and 22 of these 30 reactions occurred after day 7. In a similar study by Surtees et al,² of 132 patients referred from British general practitioners, only 4 were confirmed to have an allergy by radioallergosorbent test. The remaining 128 were given a single dose of oral penicillin and had no allergic reaction. The true incidence of allergy in patients with a history of penicillin allergy is substantially less than 10%; therefore, the cross-reaction rate between penicillins and cephalosporins must certainly be less.

The cross-reaction rate between third-generation cephalosporins and penicillin approaches 0%

Second, most of the evidence suggests that a cross-reaction between penicillin and cephalosporins is rare, perhaps no greater than that between penicillins and structurally unrelated antibiotics. Anne and Reisman³ reviewed data from published series and postmarketing reports from drug manufacturers. Serious allergic reactions to cephalosporins occur in about 0.02% of patients who take the antibiotic. The rate of serious reactions in patients with a penicillin allergy appears to be twofold to fourfold this baseline rate. However, a threefold baseline rate of serious reactions is seen in patients with penicillin allergy when they are given a structurally unrelated antibiotic.

These data suggest that a history of penicillin allergy is a general risk factor for allergic manifestations to antibiotic administration and is not specific to cephalosporins. The authors note that the initial studies that suggested a high cross-reaction between penicillin and first-generation cephalosporins were done when issues with the manufacturing process meant that cephalosporins were frequently contaminated with penicillin. The cross-reaction rate between third-generation cephalosporins and penicillin approaches 0%.³

Anne and Reisman also note that skin testing does not differentiate those patients in whom a serious reaction to cephalosporins will develop.³ The myth that a high rate of cross-allergy between penicillin and cephalosporins exists needs to be exposed so that patients who need cephalosporins will be given them whether or not they have a history of penicillin allergy. Physicians should note that patients with true penicillin allergy are at slightly increased risk of an allergic reaction when given any antibiotic.