A recent study used direct oral testing to determine whether reactions to antibiotics are actually allergic

Antibiotics – mainly penicillin and cephalosporin – are often used to treat infections in children, such as ear infections and pneumonia. Up to 10 per cent of children present with rashes while on these antibiotics and are often labelled as allergic, with no appropriate diagnostic strategy.

This results in the use of broader spectrum alternative antibiotics that may be associated with adverse events, development of resistant bacteria and more costs. In reality, the majority of these children are not truly allergic, reveals a new study published in The Journal of Allergy and Clinical Immunology: In Practice (JACI: IP).

Researchers from the Montreal Children’s Hospital (MCH) and the Research Institute of the McGill University Health Centre (RI-MUHC) conducted a study assessing the use of direct graded oral challenges (direct oral testing) to diagnose true cephalosporin allergy. Patients received initially 10 per cent of the treatment dose, then 90 per cent after 20 minutes, and reactions were monitored for one week post-challenge.

The study involved 136 pediatric patients aged 0-18 years who had presented with non-severe skin limited reaction (hives/rash) while treated with cephalosporin in the last ten years. The majority (more than 90 per cent) tolerated well a direct oral challenge. Reactions that occurred during the challenge were all mild and limited to the skin.

Making the right diagnosis

This is the first study to apply direct oral challenges to all children presenting with suspected cephalosporin allergy.

In the end, only 9.6 per cent were actually allergic to the antibiotic. Some 5.1 per cent had an immediate reaction (within one hour) and 4.4 per cent, a delayed reaction (between one and eight hours).

Dr. Moshe Ben-Shoshan, specialist in pediatric allergy and immunology at the MCH, scientist with the Infectious Diseases and Immunity in Global Health Program at the RI-MUHC and lead author of the study
Dr. Moshe Ben-Shoshan, specialist in pediatric allergy and immunology at the MCH, scientist with the Infectious Diseases and Immunity in Global Health Program at the RI-MUHC and lead author of the study

“We have demonstrated that direct graded oral challenges are safe and effective for diagnosing pediatric cases who report non-severe, skin-limited, blister-free symptoms while treated with cephalosporin,” says study lead author Dr. Moshe Ben-Shoshan, a specialist in pediatric allergy and immunology at the MCH and a scientist with the Infectious Diseases and Immunity in Global Health Program at the RI-MUHC.

More than half of the families whose children had a negative oral test agreed to be contacted again within five years (63 out of 123 children). Of these, 50.8 per cent used antibiotics again, and only three children reported mild adverse reactions. Two of these had received amoxicillin (from the penicillin family) and one had received cephalosporin.

Children with food allergies and those with a longer time lapse between the initial reaction and the oral test were more likely to react during the challenge, according to the study.

Efficiency gains and cost savings

Alternative drugs given to patients with suspected allergy to amoxicillin and cephalosporin, such as macrolides, quinolones and vancomycin, are more expensive and are associated with adverse events, the development of antibiotic resistant bacteria and prolonged hospital admission.

The study establishes that a direct graded oral challenge, without performing prior skin tests, is safe and appropriate in cases of non-severe skin reactions. Hence, it will promote optimal and cost-effective use of antibiotics in children with bacterial infections.

The authors gratefully acknowledge funding from the Canadian Institutes of Health Research.

About the study

The study Assessing Pediatric Cephalosporin Allergic Reactions Through Direct Graded Oral Challenges was conducted by Carly Sillcox, Sofianne Gabrielli, Andrew O’Keefe, Christine McCusker, Elissa M. Abrams, Thomas Eiwegger, Adelle Atkinson, Vy Kim, Ana-Maria Copaescu and Moshe Ben-Shoshan.

This study was selected as a “practice changer” article by the JACI: IP editors for the American Academy of Allergy, Asthma & Immunology.