All penicillins are cross-sensitizing and cross-reacting. Skin tests using penicilloyl-polylysine and undegraded penicillin can identify most individuals with IgE-mediated reactions (eg, hives, bronchospasm). In those patients with positive reaction to skin tests, the incidence of subsequent immediate severe reactions associated with penicillin administration is high. A history of a penicillin reaction in the past is often not reliable. Only a small proportion (less than 5%) of patients with a stated history of penicillin allergy experience an adverse reaction when challenged with the medication. The decision to administer penicillin or related medications (other beta-lactams) to patients with an allergic history depends on the severity of the reported reaction, the severity of the infection being treated, and the availability of alternative medications. For patients with a history of severe reaction (anaphylaxis), alternative medications should be used. In the rare situations when there is a strong indication for using penicillin (eg, syphilis in pregnancy) in allergic patients, desensitization can be performed. If the reaction is mild (nonurticarial rash), the patient may be rechallenged with penicillin or may be given another beta-lactam antibiotic.
Allergic reactions include anaphylaxis, serum sickness (urticaria, fever, joint swelling, angioedema 7–12 days after exposure), skin rashes, fever, interstitial nephritis, eosinophilia, hemolytic anemia, other hematologic disturbances, and vasculitis. The incidence of hypersensitivity to penicillin is estimated to be 1–5% among adults in the United States. Life-threatening anaphylactic reactions are very rare (0.05%). Ampicillin produces maculopapular skin rashes more frequently than other penicillins, but many ampicillin (and other beta-lactam) rashes are not allergic in origin. The nonallergic ampicillin rash usually occurs after 3–4 days of therapy, is maculopapular, is more common in patients with coexisting viral illness (especially Epstein-Barr infection), and resolves with continued therapy. The maculopapular rash may or may not reappear with rechallenge. Beta-lactams can induce nephritis with primary tubular lesions associated with anti-basement membrane antibodies.
If the intradermal test described below is negative, desensitization is not necessary, and a full dose of the penicillin may be given. If the test is positive, alternative medications should be strongly considered. If that is not feasible, desensitization is necessary.
Patients with a history of allergy to penicillin are also at an increased risk for having a reaction to cephalosporins or carbapenems. A common approach to these patients is to assess the severity of the reaction. If an IgE-mediated reaction to penicillin can be excluded by history, a cephalosporin can be administered. When the history justifies concern about an immediate-type reaction, penicillin skin testing should be performed. If the test is negative, the cephalosporin or carbapenem can be given. If the test is positive, there is a 5–10% chance of cross-reactivity with cephalosporins, and the decision whether to use cephalosporins depends on the availability of alternative agents and the severity of the infection. While carbapenems were considered highly cross-reactive with penicillins, the cross-reactivity appears to be minimal (1%).