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

NCT04062344 | Completed

• 2 other identifiers: APHP1902522019-A00755-52
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Betalactams Hypersensitivity

Keywords

Betalactams hypersensitivity; Children; Drug provocation testing; Bacterial resistances

Outcome Measures

Primary Outcomes (1)

• Acquisition of at least one strain of extended-spectrum betalactamase-producing enterobacteria

  Bacteriological culture with gram-negative bacteria-specific agar. Bacterial colonies will be identified by mass spectrometry (Matrix Assisted Laser Desorption Ionization technique - Time of Flight, MALDI-TOF). Antibiogram.

  24 months

Secondary Outcomes (2)

• Acquisition of at least one strain of third generation cephalosporin-resistant gram-negative bacteria

  24 months

• Metagenomic analysis of intestinal microbiota

  24 months

Study Arms (2)

Short oral drug provocation test

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

Other: Swab

Prolonged oral drug provocation test

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

Other: Swab

Interventions

Swab OTHER

Rectal swab before and after the drug provocation testing

Also known as: Rectal swab

Prolonged oral drug provocation test; Short oral drug provocation test

Eligibility Criteria

• Age: 0 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Minors in consultation at Necker Hospital

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• URC-CIC Paris Descartes Necker Cochin: collaborator
• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Necker-Enfants Malades

Paris, Paris, 75015, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Faeces

Study Officials

• Guillaume Lezmi, Doctor (PHU)

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 20, 2019
• Study Start: March 23, 2021
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

FR (1)