Acquisition of Resistant Enterobacteria During Oral Drug Challenge for Betalactams in Children
- Conditions
- Betalactams Hypersensitivity
- Interventions
- Other: Swab
- Registration Number
- NCT04062344
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Short oral drug provocation test Swab Minors performing a short (1-4 days) drug provocation test Prolonged oral drug provocation test Swab Minors performing a prolonged (5-8 days)drug provocation test
- Primary Outcome Measures
Name Time Method Acquisition of at least one strain of extended-spectrum betalactamase-producing enterobacteria 24 months 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.
- Secondary Outcome Measures
Name Time Method Acquisition of at least one strain of third generation cephalosporin-resistant gram-negative bacteria 24 months Bacteriological culture with gram-negative bacteria-specific agar supplemented with third-generation cephalosporins.
Bacterial colonies will be identified by mass spectrometry (Matrix Assisted Laser Desorption Ionization technique - Time of Flight, MALDI-TOF).
Antibiogram.Metagenomic analysis of intestinal microbiota 24 months Metagenomic analysis will be performed by high-throughout sequencing using next-generation high-throughout DNA sequencing technologies.
Trial Locations
- Locations (1)
Hôpital Necker-Enfants Malades
🇫🇷Paris, France