The investigators are conducting a prospective study to determine the safety and outcomes of placebo-controlled graded drug challenges without prior skin testing in patients with a low-risk history of antibiotic hypersensitivity reaction based on history alone. The investigators hypothesize that the rate of reaction to graded drug challenges without prior skin testing in patients with a low-risk history of drug hypersensitivity reaction based on history alone will not be meaningfully more than the rate of reaction to placebo. The investigators hypothesize that the rate of adverse reactions to drug challenges without prior skin testing will not be meaningfully more than the rate of adverse reactions with prior skin testing as was observed in the investigators' historical clinic cohort.

Graded drug challenges are the gold standard to exclude an immediate hypersensitivity reaction in patients with a low likelihood of drug allergy and are considered standard of care. Patients who tolerate a graded challenge are deemed to not be allergic to the drug and are not at increased risk for future reactions compared with the general population. Prior studies of graded challenges in appropriately selected patients have demonstrated low reaction rates with symptoms that were mainly mild and subjective in nature. The investigators are conducting a prospective study to determine the safety and outcomes of placebo-controlled graded drug challenges without prior skin testing in patients with a low-risk history of antibiotic hypersensitivity reaction based on history alone. Skin testing requires a separate visit and is, therefore, more time-consuming and costly than performing a graded challenge without skin testing. The investigators believe that they can determine if patients are at low-risk to react to an antibiotic based on a detailed history and, therefore, do not require skin testing prior to a challenge. Given the majority of symptoms to graded drug challenges reported in prior studies were mild and subjective, the investigators hypothesize that the rate of reaction to graded drug challenges without prior skin testing in patients with a low-risk history of drug hypersensitivity reaction based on history alone will not be meaningfully more than the rate of reaction to placebo. The investigators hypothesize that the rate of adverse reactions to drug challenges without prior skin testing will be not meaningfully more than the rate of adverse reactions with prior skin testing as was observed in the investigators' historical clinic cohort. All patients age 7 years or older with a history of a non-life-threatening reaction to an antibiotic are eligible to participate in a placebo-controlled graded drug challenge. The challenge is comprised of placebo followed by 30 minutes of observation, 1/10th of the treatment dose of the antibiotic the patient reported a reaction followed by 30 minutes of observation, and the full dose of the antibiotic followed by 1 hour of observation. All patients will be contacted via telephone within one month of a negative challenge to determine whether they experienced a delayed reaction. All patients will also be contacted via telephone within one year of a negative challenge to determine if they have safely taken the challenge drug.

Inclusion Criteria:

• All patients seven years of age or older who have a low-risk, non-life-threatening history of adverse reaction to an antibiotic.

Exclusion Criteria:

• Patients under the age of seven.
• Pregnant patients.
• Patients with a history of a drug reaction that is high-risk and life-threatening including life-threatening angioedema, bronchospasm, or anaphylactic shock or a history of severe non-IgE-mediated reactions including serum sickness, Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, hepatitis, hemolytic anemia, DRESS, skin and/or oral blisters, hypersensitivity vasculitis, pneumonitis, or pulmonary fibrosis.
• Patients who have taken antihistamines within 3 days of the drug challenge.

We do not plan to make IPD available to other researchers.