Skin rashes among the most common adverse effects and generally either urticarial or
maculopapular; the urticarial reactions are typical of penicillin hypersensitivity, while the
erythematous maculopapular eruptions are characteristic of ampicillin and amoxicillin and often
appear more than 7 days after commencing treatment. Such rashes may be due to
hypersensitivity to the beta-lactam moiety or to the amino group in the side-chain, or to a
toxic reaction. The occurrence of a maculopapular rash during ampicillin use does not
necessarily preclude the subsequent use of other penicillins. However, since it may be difficult in
practice to distinguish between hypersensitive and toxic responses, skin testing for
hypersensitivity may be advisable before another penicillin is used in patients who have had
ampicillin rashes. Most patients with infectious mononucleosis develop a maculo-papular rash
when treated with ampicillin, and patients with other lymphoid disorders such as lymphatic
leukemia, and possibly those with HIV infection, also appear to be at higher risk. More serious
skin reactions may occur and erythema multiforme associated with ampicillin has occasionally been reported.