Duration of Antibiotic Therapy in the Treatment of Severe Postoperative Peritonitis Admitted in ICU

Study Overview
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Brief Summary
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The investigators purpose is to demonstrate that a short antibiotic therapy (8 days) for postoperative peritonitis brings an increased number of antibiotic-free days over a 28 days period when compared to conventional (15 days) treatment.

Detailed Description
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This is a prospective randomized study involving 25 centers. Our goal is to demonstrate in the course of postoperative peritonitis that a short antibiotic therapy (8 days) compared to conventional antibiotic treatment (15 days) decreases the duration of exposure to antibiotics over a 28 days period . Patients admitted in ICU, operated for postoperative peritonitis and receiving an adequate antibiotic therapy will be identified and after informed consent is obtained will be randomized to receive a short course of antibiotic therapy (8 days) or a long course of antibiotic therapy (15 days). The primary endpoint is the number of antibiotic-free days at D28 after inclusion (analysis of superiority) . Secondary endpoints include mortality at D45 after inclusion (analysis of equivalence), the occurrence of relapse of infection, success rate of clinically and microbiologically evaluable patients, and emergence of multidrug resistant microorganisms in clinical isolates or hygiene samples. Patient data through day 45 following the initial intervention or until hospital discharge will be tracked.

Official Title
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Comparison of Two Durations of Antibiotic Therapy in the Treatment of Severe Postoperative Peritonitis Admitted in Intensive Care Unit: a Randomised Multicentre Study

Conditions
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Postoperative Peritonitis

Intervention / Treatment
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* Other: Duration of antibiotic therapy limited to 8 days


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The eligible patients have to fulfill all the following criteria patients admitted in intensive care unit in the 24 hours following surgery for postoperative intra-abdominal infection (defined as gross pus or purulent effusion within the peritoneal cavity or in one or several collections). Postoperative infection will be defined as an infection observed in a delay of 60 days following a procedure (endoscopy, surgery (abdominal, urologic, gynecologic or vascular surgery or any surgery performed in the peritoneal or retroperitoneal space) or interventional radiology) having peroperative microbiologic samples collected receiving an empiric antibiotic therapy initiated within the first 24 hours after completion of surgery with a written informed consent from the patient or the relative or the legal representative or with an emergency consent Non-inclusion criteria : Patients with one of the following criteria are eligible for the study : age<18 pregnancy Duration of stay following inclusion <72 hours neutropenia (PMN<500/mm3) due to chemotherapy or hematological disease AIDS stage C Immunosuppressive therapy or prolonged steroid therapy (≥0.5 mg/kg/d of prednisone or equivalent >1 month Bowel perforation following endoscopy treated in a delay <6 hours after injury Uterine perforation following a surgical procedure treated in a delay <6 hours after injury Moribund patient (SAPS II score >65 within 12 hours preceding inclusion) Limitation of treatment previously decided Surgery considered as non curative by the surgeon Patient included in another clinical trial evaluating an antimicrobial agent Secondary exclusion criteria: Among the eligible patients, those who have one of the following criteria will be excluded Negative culture of the peritoneal fluid Peritoneal culture exclusively fungal Inadequate empiric antibiotic therapy (not targeting all the microorganisms cultured from peritoneal or blood cultures) within 24 hours after surgery Death between D1 and D8

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 8 day-antibiotherapy<br>Duration of antibiotic therapy limited to 8 days: Antibiotics received for up to 8 days following surgery for postoperative peritonitis in patients hospitalised in intensive care unit | Other: Duration of antibiotic therapy limited to 8 days<br>* Initiation of adequate empiric antibiotics for postoperative peritonitis within 24 hours after surgery and up to 8 days. At randomisation performed on day 8, the patients assigned to the 8-day group (short-course group) stop their treatment<br>|
| No Intervention: 15 day-antibiotherapy<br>Antibiotics received for up to15 days following surgery for postoperative peritonitis in patients hospitalised in intensive care unit corresponding to usual practice and recommendations | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of antibiotic-free days at D28 after inclusion | The number of antibiotic-free days at D28 after inclusion (analysis of superiority) | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at D45 after inclusion | Mortality at D45 after inclusion (analysis of equivalence) | 45 days | 
| Duration of ICU and hospital stay | Duration of ICU and hospital stay | 45 days | 
| Changes in SOFA score | Changes in SOFA score | 8 days | 
| Number of days alive without organ failure | Number of days alive without organ failure | 28 days | 
| Failure rate for clinically evaluable patients | Failure rate for clinically evaluable patients | 28 days | 
| Failure rate for microbiologically evaluable patients | Failure rate for microbiologically evaluable patients | 28 days | 
| Rate of relapse within 45 days | Rate of relapse within 45 days | 45 days | 
| Emergence of multidrug resistant microorganisms in clinical isolates and hygiene samples | Emergence of multidrug resistant microorganisms in clinical isolates and hygiene samples | ICU discharge | 
| Total cost of antibiotic agents | Total cost of antibiotic agents | 28 days | 
| Evolution of procalcitonin plasma concentration | Evolution of procalcitonin plasma concentration | 15 days | 
| Rate of death within 45 days in specific subpopulations (elderly patients >80 years ; morbidly obese patients BMI>25kg/m2 ; severe infection with SAPSII score >40 ;peritoneal infection involving pseudomonas or enterococci ; bacteriemic infections) | Rate of death within 45 days in specific subpopulations (elderly patients >80 years ; morbidly obese patients BMI>25kg/m2 ; severe infection with SAPSII score >40 ;peritoneal infection involving pseudomonas or enterococci ; bacteriemic infections) | 45 days | 
| Total cost of hospital stay and evaluation of costs and resources impact for the hospital administration | Total cost of hospital stay and evaluation of costs and resources impact for the hospital administration | Hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative peritonitis, Intra-abdominal infection, Surgery, Laparotomy, Nosocomial infection, Antibiotic therapy, Duration of treatment, Multidrug resistant bacteria