Risk of Adverse Reactions and Cost-Effectiveness of Prophylactic Therapy Nonfatal adverse reactions, such as rash, diarrhea, and GI upset, occur commonly with the use of antimicrobials; however, only single-dose therapy is recommended for dental prophylaxis, and these common adverse reactions are usually not severe and are self-limited. Fatal anaphylactic reactions were estimated to occur in 15 to 25 individuals per 1 million patients who receive a dose of penicillin.92,93 Among patients with a prior penicillin use, 36% of fatalities from anaphylaxis occurred in those with a known allergy to penicillin compared with 64% of fatalities among those with no history of penicillin allergy.94 These calculations are at best rough estimates and may overestimate the true risk of death caused by fatal anaphylaxis from administration of a penicillin. They are based on retrospective reviews or surveys of patients or on healthcare providers recall of events. A prospective study is necessary to accurately determine the risk of fatal anaphy- laxis resulting from administration of a penicillin. For 50 years, the AHA has recommended a penicillin as the preferred choice for dental prophylaxis for IE. During these Wilson et al Prevention of Infective Endocarditis 1743 50 years, the Committee is unaware of any cases reported to the AHA of fatal anaphylaxis resulting from the administra- tion of a penicillin recommended in the AHA guidelines for IE prophylaxis. The Committee believes that a single dose of amoxicillin or ampicillin is safe and is the preferred prophy- lactic agent for individuals who do not have a history of type I hypersensitivity reaction to a penicillin, such as anaphy- laxis, urticaria, or angioedema. 