Impact of Three Probabilistic Antibiotic Therapy on Digestive Microbiota and Colonization With Multi-resistant Bacteria

N/ANot Yet RecruitingNCT07058415

Centre Hospitalier Universitaire de Nice75 enrolled

Overview

In the event of suspected osteoarticular material infection (OAMI), broad-spectrum probabilistic antibiotic therapy is recommended immediately after revision surgery. There are no efficacy data to suggest that any particular to favour any particular molecule. However, the choice may depend on the impact on the microbiota and on Enterobacteriaceae colonization with multi-resistant Enterobacteriaceae. Our aim is to evaluate three different strategies efepime+daptomycin C+D, piperacillin-tazobactam+daptomycin (PT+D) and ceftobiprole (CFB).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Osteoarticular Material Infection

Interventions

Stool sample 1

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years * Indication for prosthetic revision (PTG, PUC, PTH or hip hemiarthroplasty, PTE) or internal osteosynthesis with suspicion of IOAM following the opinion of a Réunion de concertation Pluridisciplinaire (RCP) on complex osteoarticular infections * Normal CPK level according to laboratory standard * Social security affiliation * Signature of informed consent * Negative pregnancy test for women of childbearing age. Exclusion Criteria: * Antibiotic therapy in the 3 months prior to inclusion * Clinical or radiological signs making HAI highly probable: scar discharge and/or peri-scar cellulitis fistula or abscess, bacteremia * positive bacterial culture from joint puncture or biopsy prior to revision * Chronic inflammatory bowel disease. * Previous surgical resection of small intestine or colon. * Hypersensitivity to daptomycin or any of its excipients. * Hypersensitivity to cefepime or any of its excipients or to other beta-lactamins. * Hypersensitivity to piperacillin+tazobactam or to any of the excipients or to other beta-lactamines. * Hypersensitivity to ceftobiprole or to any of the excipients or to other beta-lactamines. * Renal insufficiency with GFR \< 50ml/min/1.73 m2 (CKD-EPI). * Treatment with bosentan. * Treatment with probenecid. * Pre-existing seizure disorder. * Contraindication to L-arginine, acidosis, hyperkalemia that cannot be corrected. * Treatment with HMG-CoA reductase inhibitors. * Treatment with statins (pitavastin, pravastatin, rosuvastatin) or glyburide. * Patients in a medical emergency. * Pregnant or breast-feeding women. * Patient participating in another ongoing trial. * Mental state rendering the patient incapable of understanding this research. * Patient deprived of liberty by administrative or judicial decision.

Locations (4)

Ch Antibes

Antibes, France

Ch Cannes

Cannes, France

Ch Grasse

Grasse, France

CHU de NICE

Nice, France

Outcomes

Primary Outcomes

Compare changes in gut microbiota biodiversity between Day1 and Day5 between populations treated with C+D, PT+D and CFB in suspected Osteoarticular infection on equipment

using targeted metagenomics (16S rDNA)

Time frame: At Day 5 after starting treatment

Secondary Outcomes

Compare the evolution between Day1/end of treatment+28 Days and between Day 5/end of treatment+28D of microbiota biodiversity of each patient population treated with different antibiotics for suspected Osteoarticular infection on equipment

Simpson index,

Time frame: Up to 4 months

Compare the rate of acquisition of multidrug-resistant extended-spectrum beta-lactamase-producing intestinal Enterobacteria between antibiotic strategies on samples at Day5 and DX+28 in patients with no multidrug-resistant Enterobacteria at Day1.

Stool culture on a selective medium at Day1, Day5 and Day X+28

Time frame: Up to 4 months

Compare the rate of acquisition of carbapenemase-producing intestinal multi-resistant Enterobacteriaceae (EPC) between antibiotic strategies on samples taken at D5 and DX+28 in patients with no multi-resistant Enterobacteria at D1.

The appearance of EPC-type multi-resistant Enterobacteriaceae will be determined by stool culture on a selective medium selective medium (mSuperCARBA, MAST diagnostic) at D1, D5 and DX+28.

Time frame: Up to 4 months

Comparison of the rate of inadequacy of probabilistic strategies in the event of retained infection.

Inadequacy of one of the three probabilistic strategies will be defined by a documented infection with a bacterium resistant to both antibiotics in the case of dual therapy, or to ceftobiprole in the case of monotherapy.

Time frame: Up to 4 months

Compare the evolution between J5/JX+28 of microbiota biodiversity of patients receiving no antibiotic treatment for infection and patients in whom an infection is detected, with antibiotic treatment prescribed for 6 to 12 weeks.

Shannon index

Time frame: Up to 4 months

Piélou equitability index

Time frame: Up to 4 months

Impact of Three Probabilistic Antibiotic Therapy on Digestive Microbiota and Colonization With Multi-resistant Bacteria

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts