Drug Challenges Without Prior Skin Testing

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.