Oral Antibiotic Challenge

Graded challenge (test dosing) - Graded challenge, also known as test dosing, refers to cautious administration of a drug to a patient for testing. Graded challenge does NOT modify the allergic response to the drug. Therefore, patients who tolerate a drug during graded challenge prove that they are NOT allergic. Graded challenge also poses minimal risk of resensitization.

In the absence of antibiotic skin testing, graded challenge is appropriate when the patient's likelihood of being allergic is low. Examples include the following:

Patients who had a non-life threatening reaction to an antibiotic more than 10 years ago and have not been subsequently re-exposed.

Patients with very questionable reaction histories, although if the reaction has any features indicative of an IgE-mediated allergy, the more conservative approach to administering antibiotics is via rapid desensitization.

Patients with well documented histories of a late-onset red rash.

In contrast, patients with histories of severe non-IgE-mediated reactions (such as SJS or TEN) are NOT candidates for graded challenge because even small doses of the drug may induce severe progressive reactions.

Most graded challenges can safely be carried out in an office without intravenous access, but with preparedness to treat potential allergic reactions including anaphylaxis. The pace of the challenge and degree of caution exercised depends on the likelihood the patient may be allergic, the patient's medical stability, and the physician's experience and comfort level with the procedure.

Patients should not be pretreated with antihistamines or glucocorticoids because these agents may mask early signs of an allergic reaction. Treatment with beta-adrenergic-blocking medications should be withheld for 24 hours before challenge if feasible, as these medications can interfere with treatment of anaphylaxis, should a reaction occur. Patients with asthma, chronic obstructive lung disease or other pulmonary diseases should be optimally controlled prior to undergoing challenge.

Generally, the starting dose is usually 1/100 or 1/10 of the full dose. Ten-fold increasing doses are administered every 30 to 60 minutes until the full therapeutic dose is reached. As an example, a penicillin graded challenge could be performed as follows, with doses prepared from a standard oral suspension diluted 10-fold and then 100-fold:

Penicillin V: 5 mg, 50 mg, and 500 mg given orally at 60 minute intervals

Graded challenges can require experience to interpret properly. A minority of patients develop non-specific symptoms during the procedure, which can mimic symptoms of true allergy. Most commonly these include mouth tingling, itchng throat and lip discomfort, headache, rapid heart bear, and nausea. These may be anxiety related, and spending time with the patient explaining the safety of challenge procedures in advance may help to reduce the incidence of these nonspecific reactions.

If the patient develops convincing symptoms during or shortly after the graded challenge (within a few hours of receiving the full dose), no further antibiotics should be given and symptoms should be treated appropriately. These patients should be diagnosed with IgE-mediated antibiotic allergy and if they require a antibiotic subsequently, it should be administered via a formal desensitization.

Patients with a negative challenge may still develop delayed reactions to the drug in question, but these should not be serious. This happens in a small percentage of patients treated with a full therapeutic course of antibiotic after a negative challenge, and usually involves a red rash. In patients who have experienced multiple drug reactions, there may be some value in administering a non-sedating antihistamine during treatment with antibiotics.