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Serum Concentration of CEFOxitin Used for Antibiotic Prophylaxis in Obese Patients Undergoing BARiatric Surgery

Not Applicable
Completed
Conditions
Obese
Antibiotic Prophylaxis
Bariatric Surgery Candidate
Interventions
Drug: Serum dosage of antibiotic prophylaxis CEFOXITIN
Registration Number
NCT03306290
Lead Sponsor
Central Hospital, Nancy, France
Brief Summary

Obesity is a pandemic problem in modern societies. Bariatric surgery (gastric by-pass and sleeve gastrectomy) has emerged as an efficient treatment to reduce morbidity and mortality related to obesity. Obesity and bariatric surgery are known to be risk factors of surgical site infections (SSI). The occurrence of SSI increases health cost and the duration of hospitalization. However, an appropriate antibiotic prophylaxis has been shown to reduce SSI. As recommended by several national societies, the antibiotic prophylaxis dose should be increased in the severely obese population. However, this recommendation lies on a low level of evidence. Besides, great disparities regarding obese patient antibiotic prophylaxis exist between countries and adequate doses are still not clearly defined. In France, for instance, the intravenous second generation cephalosporin CEFOXITIN is used for antibiotic prophylaxis in bariatric surgery at the initial loading dose of 4g (2-fold that of non-obese population) at the beginning of surgery.

Obese patients have increased risk of under-dosage due to modification of their pharmacokinetics (fat/lean mass, distribution volume, renal clearance, etc.). Only few studies, all investigating a low amount of patients, evaluated the appropriateness of intraoperative antibiotic prophylaxis dosage of different betalactam and cephalosporin in the obese population. This population was more likely to be under-dosed.

The aim of this study is to analyse the appropriateness of the reference dose of intravenous Cefoxitin used as antibiotic prophylaxis in severely obese patients undergoing bariatric surgery. This will be a 2-year prospective monocentric study held in the University Hospital of Nancy, France. A large group of obese patients (\~300) will be included. Serial serum concentration measurements of Cefoxitin will be performed before, during, and at skin closure of the bariatric surgery. This study will give insights in pharmacokinetics of the antibiotic prophylaxis in the obese population and will help to determine the initial dosage and the optimal method for antibiotic prophylaxis administration.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
200
Inclusion Criteria
  • Age ≥ 18 years-old,
  • Severely obese patient with a BMI ≥ 35 kg.m-2,
  • Scheduled bariatric surgery: gastric by-pass or sleeve gastrectomy,
  • Affiliated to social security,
  • The patient is able to consent to clinical research and has received all information on the study design/protocol,
  • Signed/written informed consent
Exclusion Criteria
  • Refuse to consent to the study or the patient is unable to consent,
  • Allergy/Anaphylaxis to beta-lactam (ß-lactam) antibiotics either proven or suspected,
  • Pregnancy,
  • Persons deprived of their liberty by judicial or administrative decision,
  • Urgent or emergent surgery.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Bariatric surgery candidateSerum dosage of antibiotic prophylaxis CEFOXITINPatients included in this study belong to this arm and put up with intervention "Serum dosage of antibiotic prophylaxis CEFOXITIN"
Primary Outcome Measures
NameTimeMethod
Serum concentration of Cefoxitin at the beginning and end of the surgery with one extra measurement at halfway surgerybaseline

Blood samples will be put at low temperature for transportation and then analysed by chromatographic method

Secondary Outcome Measures
NameTimeMethod
Pharmacokinetic parameters: drug clearancebaseline

These parameters will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.

o Clearance: Cl=k x Vd

Pharmacokinetic parameter: volume of distributionbaseline

This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.

o Volume of distribution: D0/C0

Pharmacokinetic parameter: half-lifebaseline

This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.

o Half-life: t1/2=ln2/k

Pharmacokinetic parameter: elimination ratebaseline

This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.

o Elimination rate: k=(LnC0-LnC2)/(t2-t0)

Incidence of deep incisional surgical site infection (SSI) at 30 daysup to 30 days after surgery

Deep incisional SSI at 30 days defined by:

date of event for infection occurs within 30 days after the operative procedure AND involves deep soft tissues of the incision (e.g., fascial and muscle layers) AND patient has at least one of the following:

1. purulent drainage from the deep incision,

2. a deep incision that spontaneously dehisces, or is deliberately opened or aspirated by a surgeon, attending physician or other designee and organism is identified by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment (e.g., not Active Surveillance Culture/Testing (ASC/AST) or culture or non-culture based microbiologic testing method is not performed AND patient has at least one of the following signs or symptoms: fever (\>38°C); localized pain or tenderness.

3. an abscess or other evidence of infection involving the deep incision that is detected on gross anatomical or histopathologic exam, or imaging test.

Identification of factors that may be associated with the risk of under-dosagebaseline

effect of type of surgery on cefoxitine concentration

Pharmacokinetic parameter: area under curve,baseline

This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.

o Area under curve: AUC=C0/k

Incidence of superficial incisional surgical site infection (SSI) at 30 daysup to 30 days after surgery

o Superficial incisional SSI: at 30 days defined by:

Date of event for infection occurs within 30 days after any operative procedure AND involves only skin and subcutaneous tissue of the incision AND the patient has at least one of the following:

1. purulent drainage from the superficial incision,

2. organisms identified from an aseptically-obtained specimen,

3. from the superficial incision or subcutaneous tissue by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment (e.g., not Active Surveillance Culture/Testing (ASC/AST),

4. superficial incision that is deliberately opened by a surgeon, attending physician or other designee and culture or non-culture based testing is not performed AND patient has at least one of the following signs or symptoms: pain or tenderness;localized swelling; erythema; or heat,

5. diagnosis of a superficial incisional SSI by the surgeon or attending physician or other designee.

Incidence of organ/space surgical site infection (SSI) at 30 daysup to 30 days after surgery

Organ/Space SSI at 30 days defined by:

Date of event for infection occurs within 30 after the operative procedure AND infection involves any part of the body deeper than the fascial/muscle layers, that is opened or manipulated during the operative procedure AND patient has at least one of the following:

1. purulent drainage from a drain that is placed into the organ/space

2. organisms are identified from an fluid or tissue in the organ/space by a culture or non-culture based microbiologic testing method

3. an abscess or other evidence of infection involving the organ/space that is detected on gross anatomical or histopathologic exam, or imaging test evidence suggestive of infection AND meets at least one criterion for a specific organ/space infection site listed: intraabdominal infection, not specified elsewhere including gallbladder, bile ducts, liver, spleen, pancreas, peritoneum, subphrenic or subdiaphragmatic space

Trial Locations

Locations (1)

Central Hospital

🇫🇷

Vandoeuvre les Nancy, France

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