How do we know if we are allergic to antibiotics?

¿Cómo saber si somos alérgicos a los antibióticos?

Although there are few cases, allergic reactions to antibiotics can occur for many reasons, such as genetics or an excessive reaction of the immune system

Rash, swelling, breathing difficulties… Do you know someone who has suffered these symptoms after taking medicine?

Perhaps the first idea before going to the doctor is to think that it is an allergy.

However, we must be very cautious: actually, only between 6 and 10% of suspected cases are confirmed as an allergic reaction to the drug.

Allergic reactions are only those that are produced by a well-defined immune mechanism.

In all other cases, it may be other adverse reactions such as a side effect or an intolerance.

Beta-lactam antibiotics, such as penicillins and cephalosporins, are the second most consumed type of medicine in Spain.

These are responsible for most allergic reactions to medications.

Why is it important to confirm if we are allergic?

The answer is clear: for the health of the patient, who will know if he really should avoid this antibiotic or can take it when he needs it.

If, faced with a suspected allergy, it is not confirmed and the drug is avoided, most would do it unnecessarily.

In addition, the prescription of alternative antibiotics, usually more expensive and less safe, raises the cost of healthcare and can contribute to the development of resistance.

How does an allergy to antibiotics occur?

Allergic reactions to antibiotics are also known as hypersensitivity reactions.

They are an abnormal response that is produced by the interaction between the antibiotic and our immune system.

The most accepted mechanism to explain allergy to beta-lactam antibiotics is the “hapten hypothesis”.

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These drugs act as haptens, low molecular weight substances that cannot induce an immune response on their own, only after binding to proteins.

A portion of the structure formed after antibiotic-protein binding can now be recognized by components of the immune system.

This portion is called the “antigenic determinant” or “epitope” and is made up of a part of the protein bound to a structure derived from the parent drug.

Immediate allergic reactions to beta-lactams are those that appear within the first hour after taking the antibiotic.

The development of this type of reaction occurs in two stages.

The first, the sensitization stage, occurs the first time we are in contact with the antigen (antibiotic-protein conjugate).

Specific IgE-like antibodies have generated that bind to the surface of cells called mast cells and basophils.

In the second, the effector stage, the antigen binds to at least two nearby IgE and this leads to the release of molecules that promote inflammation. Then the allergy symptoms appear.

How to know if we are allergic or not?

Tests in vitro They are performed in the laboratory, using a small amount of the patient’s blood or serum.

The basophil activation test (BAT) detects the presence of IgE on the surface of basophils.

In recent years, the BAT is gaining strength for the diagnosis of allergy to antibiotics, however, should be used in combination with tests in vivoto to achieve good sensitivity (ability to detect allergic cases).

On the other hand, immunoassays are based on the detection of IgE in serum.

Currently, the radioallergosorbent test (RAST) is practically the only method in vitro with adequate sensitivity to detect the extremely small amount of IgE present in cases of allergy to antibiotics.

The patient’s serum is incubated with cellulose discs containing the antibiotic-protein conjugate implicated in the allergy.

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Subsequently, the patient’s IgE that recognizes the antigenic determinant is detected using a radioactively labeled secondary antibody.

Despite its sensitivity, some drawbacks of RAST are that it is a non-automated home method and the use of radioactivity.

Also, it cannot be used for beta-lactams like clavulanic acid.

Tests in vitro are performed in the laboratory, using a small amount of blood or serum from the patient.

The basophil activation test (BAT) detects the presence of IgE on the surface of basophils.

In recent years, the BAT is gaining strength for the diagnosis of allergy to antibiotics, however, it must be used in combination with in vivo tests to achieve good sensitivity (ability to detect allergic cases).

On the other hand, immunoassays are based on the detection of IgE in serum.

Currently, the radioallergosorbent test (RAST) is practically the only method in vitro with adequate sensitivity to detect the extremely small amount of IgE present in cases of allergy to antibiotics.

The patient’s serum is incubated with cellulose discs containing the antibiotic-protein conjugate implicated in the allergy.

Subsequently, the patient’s IgE that recognizes the antigenic determinant is detected using a radioactively labeled secondary antibody.

Despite your sensitivity, some drawbacks of RAST are that it is a non-automated home method and the use of radioactivity.

Also, it cannot be used for beta-lactams like clavulanic acid.

Chemistry to the rescue

The lack of sensitivity of the immunoassays is due to the fact that the antibiotic-protein conjugate used does not correspond to the one formed. in vivo.

In this way, the IgE of patients do not recognize it and its presence cannot be detected in serum.

Therefore, knowing the structure derived from the antibiotic that is part of the antigenic determinant is of vital importance to advance in the development of effective in vitro tests.

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Chemistry is a great help for the identification and characterization of the antigenic determinants of beta-lactam antibiotics.

The amino groups of the lysines present in proteins react with the carbonyl group of the beta-lactam ring, which opens.

In the case of penicillins such as amoxicillin and benzylpenicillin, this open protein-bound structure is stable and is known to be involved in an allergy to these drugs.

However, other beta-lactams such as cephalosporins or clavulanic acid have somewhat more complex chemistry.

This has long prevented the identification of the exact antigenic determinants involved in the allergic reaction to these drugs.

Recently, they have taken carried out several studies based on chemical approximations to improve the diagnosis in vitro of allergy to beta-lactam antibiotics.

On the one hand, synthetic antigenic determinants for cefaclor and clavulanic acid have been prepared in the laboratory.

Their subsequent immunological evaluation has shown that they are recognized in vitro by IgE from patients allergic to these antibiotics.

This means that they are similar structures that causing the allergic response in vivo.

On the other hand, with the objective of replacing radioactivity with fluorescence in immunoassays, a molecule has been designed that allows the fluorescent signal to be increased and could be used for the labeling of secondary antibodies.

In addition to these studies, a trend A very interesting future is the automated, sensitive, rapid, and simultaneous detection of allergy to various beta-lactam antibiotics.

The research carried out by chemists and allergists, if it continues on the right track, can contribute to the fact that in the future all cases of allergy to beta-lactam antibiotics can be confirmed by a quick and safe diagnosis.

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