Antibiotic allergy: a common problem in cystic fibrosis patients

Cystic fibrosis causes the production of viscous mucus and chronic bacterial colonization in the respiratory tract, causing recurrent lung infections. These require the administration of intravenous antibiotics at high doses, for a prolonged period of time. Therefore, adverse reactions to antibiotics are common in the cystic fibrosis population. Some reactions are predictable, while others are not (called unpredictable).

Predictable reactions are not allergic in nature (Table 1). This category includes:

• side effects: for example, the appearance of cutaneous hypersensitivity to the sun in a patient receiving ciprofloxacin;

• interactions: for example, the significant reduction in the elimination of alcohol in a patient treated with metronidazole, causing nausea, vomiting, palpitations and headaches when taken concurrently;

• toxic reactions: for example, the onset of a hearing disorder as a result of the use of aminoglycosides (tobramycin).

These reactions are well described in the documentation that accompanies the antibiotic. They can generally be avoided if the patient reads the sheet accompanying the medication and discusses it with his doctor or pharmacist.

Moreover, some reactions are unpredictable. The latter can be divided into two groups: pseudo-allergic reactions and allergic reactions. The first involve the direct release of chemical mediators involved in allergy, without the immune system being activated. The direct release of mediators is caused by exposure to agents that are generally recognized (iodine contrast during a radiological examination, opiates, non-steroidal anti-inflammatory drugs). The manifestations vary: rhinitis, asthma, urticaria, and low blood pressure. These pseudo-allergic reactions are infrequent. In patients who have already experienced such a reaction, premedication prior to exposure to the causative agent (e.g. prednisone and diphenhydramine) is generally effective.

True allergic reactions caused as a result of the administration of an antibiotic are three times more common in patients with cystic fibrosis than in the general population. Allergy rates reported in various studies range from 1.9 to 28%. However, piperacillin is consistently reported to be the antibiotic associated with the greatest risk of reaction, accounting for 33 to 50% of reported events. However, this statistic must be nuanced by the fact that piperacillin is one of the antibiotics most used during exacerbations. Intravenous administration is associated with a greater risk of
develop an allergy.

Allergic reactions occur as a result of the triggering of an immune system response caused by repeated exposure to a given antibiotic. They are grouped into four types:

• type I is linked to the development of antibodies (IgE) against the antibiotic: the reaction occurs rapidly after administration and includes urticaria, edema, asthma up to anaphylactic shock, potentially fatal if not treated;

• type IV is linked to the development of a group of white blood cells, the T cells, directed against the antibiotic: this reaction occurs later, generally by various types of skin damage;

• types II and III are rarely encountered during antibiotic allergies.

The diagnosis of drug allergy is mainly based on a detailed questionnaire. The elements sought are the name of the suspected drug, the indication for treatment, the symptoms during the reaction and their evolution, the presence of these symptoms before the reaction and the treatment of the reaction.

When an allergic reaction to an antibiotic is suspected, it is sometimes possible to do skin tests. During the scarification test, a drop of antibiotic is placed on the skin of the forearm and then the skin is scratched with a needle. During the intradermal test, a drop of antibiotic is injected under the first layer of the skin. A reaction of redness and swelling at the site is indicative of an allergy.

When the tests are negative on the skin or when it is not possible to perform skin tests, a provocation test is carried out. Different doses of antibiotics are administered fractionally: generally, we start with 1/100 of the dose, then 1/10 and finally a complete dose. The antibiotic is given orally or intravenously. This method makes it possible to verify the presence of type I allergy (IgE antibodies). Since it involves the risk of an anaphylactic reaction, it should always be done in a hospital setting under medical supervision. During a delayed reaction (type IV), a rash may occur in the days following the test. It must absolutely be reported to the allergist who carried out the test. New techniques are currently being studied for the investigation of these delayed reactions, such as patch tests.

When an allergic reaction is suspected, the first treatment is to stop taking the medication in question. Antihistamines will be given followed by corticosteroids and adrenaline depending on the severity of the underlying reaction.

If an allergy to an antibiotic is confirmed, strict avoidance of this medication by the entire family remains the best course of action. When the antibiotic in question is essential, desensitization may be used. To do this, the drug is administered at infinitesimal doses, generally 1/100,000 of the target dose, then the dose is gradually increased until the therapeutic dose is administered. This procedure lasts more than eight hours and should take place in intensive care, as it involves the risk of an allergic reaction. Desensitization provides temporary tolerance for the duration of treatment. As soon as treatment is stopped, the allergic condition returns to the level prior to desensitization. Further desensitization should be performed each time the antibiotic is to be administered.

In short, the most important element is to properly document the reactions that have occurred following the use of a particular antibiotic, both to prevent the onset of a predictable reaction and to avoid unduly depriving yourself of a beneficial therapeutic weapon.

Hugo Chapdelaine
MD, FRCPC Allergo-immunologist Notre-Dame Hospital

Hospital center
University of Montreal (CHUM)

Scientific review

Louis Paradis M.D., FRCPC Allergo-immunologist Hospital Center
academic
Sainte-Justine Notre Dame Hospital

Hospital center
University of Montreal (CHUM)

Montreal (Quebec) Canada

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