De‐labelling antibiotic allergy through five key questions

The selection of an antibiotic for treatment of bacterial infection should ideally be based on clinical findings, guideline recommendations, and microbiological test results. Meanwhile, up to 10% of the European and North American population report to be allergic to penicillin (1). Once a suspicion of allergy is made, treating physicians find themselves forced to administer alternative antibiotics, even if a β-lactam would be the antibiotic of choice.


De-labelling antibiotic allergy through five key questions
To the Editor, The selection of an antibiotic for treatment of bacterial infection should ideally be based on clinical findings, guideline recommendations and microbiological test results. Meanwhile, up to 10% of the European and North American population report to be allergic to penicillin. 1 Once a suspicion of allergy is made, treating physicians find themselves forced to administer an alternative antibiotic, even if a β-lactam would be the antibiotic of choice. As a result, suspected allergy to standard antibiotics commonly triggers the inappropriate use of broad-spectrum or reserve antibiotics and may thus catalyse the problem of microbial resistance.
In order to meet this important topic, allergists around the world need to ensure that documents attesting antibiotic allergy are only issued after thorough history and appropriate testing. If immediate allergy testing in case of an acute infection is not an option due to the lack of time or equipment, the risk of antibiotic allergy should be categorized as being high or low to determine whether the use of alternative antibiotics is really necessary. Several algorithms aiming to question pre-existing labels of antibiotic allergy have been published in recent years. [2][3][4] While the proposed algorithms accurately consider different reaction patterns by covering the frequent to the extremely rare, they tend to be complex, time-consuming and hardly suitable for everyday practice.
Patients attending our clinic between January 2017 and May 2019 underwent standardized questioning whenever a history of antibiotic allergy was given. If antibiotic therapy was necessary, the medication of first choice was administered even if an allergy to this antibiotic or corresponding class of antibiotics was reported-provided that allergy was considered unlikely according to our algorithm ( Figure 1). The antibiotic was administered in all cases under close medical supervision, either as part of inpatient treatment of an infection or in context of a controlled provocation after negative skin testing. During provocation testing in the outpatient clinic, patients were monitored until 4 hours after the last dose; they were advised to present for objective examination if any symptoms developed within the next days.
The evaluated algorithm is based on the assumption that antibiotic allergy most commonly triggers either an acute anaphylactic reaction within a few minutes of intake or infusion or an exanthematous skin rash beginning several hours to days later. 5,6 Question one ( Figure 1) aims to identify patients with a history of pharmacological side-effects or any complaints unrelated to antibiotic treatment.
This includes a history of urticaria or exanthem if the onset was more than two days or more than one week, respectively, after discontinuation of antibiotic treatment. The question is to be answered with "no" in cases who are unable to reliably discriminate urticaria from exanthem. An urticarial or exanthematous rash in childhood and adolescence is mostly caused by bacterial or viral infections, 7 while genuine allergy is rare (question two).
Question three was developed to discern IgE-mediated anaphy- Claims of allergy commonly hamper guideline-directed antibiotic therapy and trigger the use of alternative antibiotics, which may be less effective, have more side-effects and/or promote the development of microbial resistance. 8 Correction of unjustified allergy claims constitutes a pivotal element in the fight against increasing antibiotic resistance. 9 Targeted questioning according to the presented algorithm permits to remove the label of antibiotic F I G U R E 2 The algorithm was applied in 200 cases. A total of 124 patients tolerated the incriminated antibiotic without any reaction: 82 cases in form of a therapeutic administration because antibiotic treatment was urgently needed, 42 in a controlled provocation after negative skin testing allergy in the majority of cases. Though questionnaire-based de-labelling does not fully exclude a reaction upon re-exposure of the antibiotic in question, the risk of a severe reaction is considered to be low.
However, further validation studies are needed to evaluate the proposed algorithm, in populations including a substantial proportion of patients with confirmed antibiotic allergy, in order to determine its sensitivity and specificity.

CON CLUS ION
Guideline-directed anti-infectious therapy is commonly hampered by reports of antibiotic allergy. Standardized questioning permits the administration of first-line antibiotic treatment in a substantial proportion of cases by sorting out unjustified suspicions while reliably identifying potential high-risk patients.
Although the development of an algorithm to reduce unnecessary prescription of alternative antibiotics is likely to be feasible and safe, formal validation using a methodologically rigorous approach is required before such an algorithm may be implemented for routine application.

CO N FLI C T O F I NTE R E S T
The authors declare no conflict of interest.

AUTH O R CO NTR I B UTI O N S
AT initiated data evaluation. AR, KR, AT and JS analysed and inter- Axel Trautmann https://orcid.org/0000-0001-6751-7328