Acquisition of Resistant Enterobacteria During Oral Drug Challenge for Betalactams in Children

NCT ID: NCT04062344

Last Updated: 2024-10-30

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-03-23
• Study Completion Date: 2025-03-31

Brief Summary

Direct drug provocation testing, without prior skin or in vitro testing, is the reference standard for confirming the diagnosis of drug hypersensitivity reactions in children reporting mild and delayed-onset reactions. However, optimal protocol(s) have not been standardized. Although a 2-days' provocation testing protocol is effective, increasing its duration (up to 14 days) may improve its diagnosis performance without increasing the risk of severe reactions. However, a prolonged provocation testing could increase the risk of emergence of bacterial resistances in the digestive flora. Longer duration could be associated with the emergence of extended-spectrum betalactamase producing enterobacteria. However, this point has never been confirmed.

The study will include children (0-18 years); referring for histories of mild and delayed-onset reactions to betalactams. drug provocation testing will be performed with the suspected BLs in our department, as in clinical practice. Two groups of patients will be compared: a group performing short provocation testing (arbitrary defined as lasting 1 to 4 days) and a group with prolonged drug provocation testing (arbitrary defined as lasting 5-8 days). A rectal swab will be collected for each patient before the provocation testing, a second one at the end of the provocation testing. Each sample will be analyzed to detect the presence extended-spectrum betalactamase -producing enterobacteria.

Detailed Description

Drug hypersentivity in children is suspected in up to 10% of parents. However, drug hypersensitivity is rarely confirmed: its prevalence in children is estimated to be less than 0.5%. The most frequently suspected drugs are betalactams such as amoxicillin and oral cephalosporins (cefpodoxime, cefixime, cefuroxime). Most reported drug hypersensitivity reactions to betalactams in children are mild and delayed-onset, typically starting more than one hour after the first dose. These reactions often include urticaria, maculo-papular rashes, and/or edema. Amoxicillin is indicated as a first-line therapy in the majority of common infections in children. Suspicion of betalactams hypersensitivity is associated with the prescription of alternate antibiotics often less effective and that may increase the risk of bacterial resistance, morbidity and health costs. Therefore it is necessary to confirm or exclude a true betalactams hypersensitivity.

Direct drug provocation testing without prior skin or in vitro testing, is the reference standard for confirming the diagnosis of drug hypersensitivity reactions in children reporting mild and delayed-onset reactions. However, optimal protocol(s) have not been standardized. Although a 2-days' drug provocation testing protocol is effective, increasing its duration (up to 14 days) may improve its diagnosis performance without increasing the risk of severe reactions. However, a prolonged drug provocation testing could increase the risk of emergence of bacterial resistances in the digestive flora. Longer duration could be associated with the emergence of extended-spectrum betalactamase producing enterobacteria. However, this point has never been confirmed.

The aim of this study is to determine whether the risk of emergence of ESBL-producing bacteria in the digestive flora is higher in case of prolonged drug provocation testing.

Our hypothesis is that the acquisition rate of extended-spectrum betalactamase -producing enterobacteria will be higher in prolonged drug provocation testing.

As previously published, in the Pediatric Pulmonology and Allergy Department of the Necker Hospital, we perform direct drug provocation testing with the culprit drug in children with histories of mild delayed-onset reactions. Drug provocation testing is prolonged at home at normal therapeutic doses. The duration of the drug provocation testing is 1-2 days more than the chronology of the index reactions, with a maximum of eight days.

The study will include children (0-18 years), referring for histories of mild and delayed-onset reactions to betalactams. drug provocation testing will be performed with the suspected betalactam in our department, as in clinical practice. Two groups of patients will be compared: a group performing short drug provocation testing (arbitrary defined as lasting 1 to 4 days) and a group with prolonged drug provocation testing (arbitrary defined as lasting 5-8 days). A rectal swab will be collected for each patient before the drug provocation testing, a second one at the end of the drug provocation testing. Each sample will be analyzed to detect the presence extended-spectrum betalactamase -producing enterobacteria.

Conditions

Betalactams Hypersensitivity

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Short oral drug provocation test

Minors performing a short (1-4 days) drug provocation test

Swab

Intervention Type: OTHER

Rectal swab before and after the drug provocation testing

Prolonged oral drug provocation test

Minors performing a prolonged (5-8 days)drug provocation test

Swab

Intervention Type: OTHER

Rectal swab before and after the drug provocation testing

Interventions

Swab

Rectal swab before and after the drug provocation testing

Intervention Type: OTHER

Other Intervention Names

Rectal swab

Eligibility Criteria

Inclusion Criteria

• Minors aged 0 to 18
• Consultation in Necker for an oral drug provocation test to explore mild (urticaria, edema, maculo-papulous exanthema) delayed-onset reaction (1 hour after initiation of treatment) to betalactams (amoxicillin +/-clavulanic acid, cefpodoxime, cefixime, cefuroxime)

Exclusion Criteria

• Minors with potentially severe delayed-onset reactions (painful skin lesions, atypical target lesions, erosions of mucosa, centro facial oedema, purpuric infiltrated papules) or severe (Lyell/Stevens Johnson Syndrome, fixed drug eruption, acute generalized exanthematous pustulosis, skin rash with systemic and hypereosinophilic disorders)
• Antibiotic treatment within the past month before the drug provocation test
• Travel abroad within the past 6 months before the drug provocation test
• Cardio-respiratory failure, renal failure, hepatic impairment or any other severe chronic pathology

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guillaume Lezmi, Doctor (PHU)

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Necker-Enfants Malades

Paris, Paris, France

Site Status: RECRUITING

Countries

France

Central Contacts

Guillaume Lezmi, Doctor (PHU)

Role: CONTACT

guillaume.lezmi@aphp.fr

+33 1 44 49 48 38

Hélène Morel

Role: CONTACT

helene.morel@aphp.fr

+ 33 1 71 19 63 46

Facility Contacts

Guillaume Lezmi, Doctor (PHU)

Role: primary

guillaume.lezmi@aphp.fr

+33 1 44 49 48 38

Hélène Morel

Role: backup

helene.morel@aphp.fr

+33 1 71 19 63 46

Other Identifiers

2019-A00755-52

Identifier Type: OTHER

Identifier Source: secondary_id

APHP190252

Identifier Type: -

Identifier Source: org_study_id