Clinical trial NCT05308849: Peritoneal Diffusion and Efficacy of Antibiotic Therapy in Pediatric Peritonitis
Official title: Peritoneal Diffusion and Efficacy of Antibiotic Therapy in Pediatric Peritonitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Peritonitis
Appendicitis
Children, Only
Antibiotic Toxicity
Keywords: Children Peritonitis
Antibiotic diffusion
Pharmacocinetic study
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
Collaborators: name: PAPE Elise
First posted: 2022-04-04
Enrollment: 41
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This is a pilote monocentric prospective study about pediatric peritonitis and antibiotics pharmacokinetic and pharmacodynamic. The investigators will include 41 patients between 3 and 17 years-old during 2 years in the University Hospital of Nancy.

The aim of this study is to determine if the beta-lactam dosages in children recommended by the guidelines for management of intra-abdominal infections permitted the achievement of adequatly serum and peritoneal concentrations in the medical and surgical management of peritonitis.

The investigators will collected serum and peritoneal fluid samples at 3 different times: peritoneal incision, end of surgery, 2 days and 5 days after surgery in order to compare the concentrations and the minimal inhibitor concentration of bacteria.

The hypothesis is that of a serum and peritoneal antibiotic under dosage.

Detailed description: Pediatric population with localized or generalized appendicular peritonitis with surgical management at the Nancy University Hospital.

Patients are usually taken in emergency at the Pediatric Emergency Department (Children's Hospital, CHRU Nancy). The diagnosis of peritonitis is then made or confirmed by clinical examination and paraclinical tests (biology and imaging).

Written informed consent is obtained from one of the parental authority holders, allowing inclusion in the study. An information document adapted to the child's understanding will also be sent to him/her. The child's non-opposition will be sought if he/she is old enough to understand. The information will be given jointly to the child and to the legal guardians present at the patient's bed at the time of diagnosis of peritonitis. The reflection period will correspond to the interval between this information and the management in the operating room. This may vary depending on the occupation of the operating room.

The diagnosis of appendicular peritonitis is made by the surgeon (routine care). The child is included.

Antibiotic therapy is started IV according to the protocol in force at the CHRU (routine care):

- Cefotaxime (200 mg/kg/d, 4 IV administrations) + Metronidazole (20-30 mg/kg/d, 3 IV administrations)+/-Gentamicin (3-8 mg/kg/d IV)

Specific biological samples and collections are taken for the research:

* A blood sample (1mL) (S0) after injection of the antibiotic and before appendicular section, non-invasive because performed on peripheral venous route.
* A blood sample (1mL) (S1) at the end of the operation, either when the peripheral venous route is placed if possible (non-invasive), otherwise at the periphery (invasive).
* If a drainage of the peritoneal cavity is in place, a non-invasive collection of peritoneal fluid (5 mL) on the drain will be performed (P1) at D2.
* If generalized peritonitis, an additional blood collection (1mL) at D5 (S2) during the biological check-up (routine care). If an abdominal drainage is still in place, a non-invasive collection of peritoneal fluid (5mL) on drain will be performed (P2). At D5, the patients are under appropriate antibiotic therapy.

Specifically for research, betalactam assays are performed on S0, S1, S2, P0, P1 and P2 once all samples have been sent to Pharmacology.

Bacteriological analyses are performed on P0 (routine care), P1 and P2 in real time.

The following specific data will be collected: time of first antibiotic administration, time of sampling (S0, S1 and P0), time of surgery start. Data concerning antibiotic therapy (dosage, frequency of administration) will be collected during the entire hospitalization period as well as the time of the other samples if applicable (S2, P1 and P2).

Clinical and biological data are collected, including the visit at 4-6 weeks after discharge. (In routine care, a visit at 1 month post-op is performed). The investigator looks for AEs or SAEs. At the end of this post-operative visit, the patient is discharged from the study.

The volume of blood collected in the framework of the research is estimated at 3mL, i.e. less than 2.5% of the total blood volume over the inclusion period. The maximum total volume collected is 24 mL (6 mL for research, 18 mL for care, i.e. 3 samples of CBC, blood ionogram and CRP).

Blood and peritoneal samples :

The 3 blood samples as well as the 2 (possibly 3) peritoneal samples will be taken by a nurse and will be placed in a specific bag. Each sampling time will be clearly identified on the sample and a traceability form will be completed and sent to the Pharmacology and Toxicology laboratory.

Eligibility criteria: Inclusion Criteria:

* diagnosis of intra-abdominal infection : localized or generalized peritonitis secondary to appendix

Exclusion Criteria:

* betalactams allergy
* peritonitis with other etiology than appendix
* antibiotic treatment longer than 24h

Primary outcomes:
measure: antibiotic concentration
timeFrame: Peritoneal incision, end of surgery, Day+5 after surgery if systemic peritonitis,
measure: antibiotic concentration
timeFrame: During surgery, Day+2 after surgery if drain peritonal, Day+5 after surgery if systemic peritonitis,
Secondary outcomes:
measure: Determine elimination rate constant Kel
timeFrame: Statistical analysis after 2 years of inclusion
measure: Determine estimated initial concentrationf C0
timeFrame: Statistical analysis after 2 years of inclusion
measure: Determine Area Under the Curve AUC.
timeFrame: Statistical analysis after 2 years of inclusion
measure: Determine Half-life
timeFrame: Statistical analysis after 2 years of inclusion
measure: Determine distribution volume
timeFrame: Statistical analysis after 2 years of inclusion
measure: Determine Clearance or betalactams in children
timeFrame: Statistical analysis after 2 years of inclusion
measure: Evaluate the relationship between serum and peritoneal concentrations of beta-lactam
timeFrame: Statistical analysis after 2 years of inclusion
measure: Proportion of different bacteria
timeFrame: Statistical analysis after 2 years of inclusion
measure: Proportion of sensitive and resistant germs to betalactam antibiotics
timeFrame: Statistical analysis after 2 years of inclusion
measure: Description of minimal inhibition concentration for bacterias
timeFrame: Statistical analysis after 2 years of inclusion
measure: Factors associated with an antibiotic under-dosage
timeFrame: Statistical analysis after 2 years of inclusion
measure: Factors associated with an antibiotic overdose
timeFrame: Statistical analysis after 2 years of inclusion
measure: Evaluation of duration of hospitalization
timeFrame: Statistical analysis after 2 years of inclusion
measure: Mean delay for apyrexia
timeFrame: Statistical analysis after 2 years of inclusion
measure: Clinical complications
timeFrame: Statistical analysis after 2 years of inclusion
Other outcomes:
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