Efficacy of Temocillin in Urinary Tract Infection Due to ESBL Producing and AmpC Hyperproducing Enterobacteriaceae
- Registration Number
- NCT02681263
- Lead Sponsor
- University Hospital, Grenoble
- Brief Summary
The present study aims at demonstrating the efficacy of temocillin in the treatment of UTI requiring parenteral therapy due to a confirmed ESBL producing or AmpC hyperproducing Enterobacteriaceae, resistant to quinolones and Bactrim® in France. In addition, this study will describe and support the use of high dose (6g/day) of temocillin which could be of interest for the treatment urinary tract infection due to multi-resistant bacteria having high MIC (up to 32 mg/L). The investigators will also evaluate the tolerance of the drug by monitoring the adverse event and the incidence of eventual Clostridium difficile associated infection.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 25
- Age of at least 18 year old
- Patient benefits from social security
- Signed informed consent
- A urinary tract infection due to a confirmed ESBL producing strain (detected by the use of a rapid diagnostic test applied on the urine) requiring parenteral antimicrobial therapy
- Hospitalized patient
- For women able to procreate: Use of an acceptable method of birth control throughout the study. Acceptable methods of birth control are: oral contraceptives, intrauterine device (IUD), diaphragm with spermicide and condom. (All forms of hormonal contraception are acceptable
- Patient infected with a bacteria which is not an ESBL-producing or AmpC hyperproducing Enterobacteriaceae
- Patients infected with a strain sensible to both fluoroquinolones and trimethoprim/sulfamethoxazole
- Patients infected with a strain resistant to temocillin
- Hospital-acquired urinary tract infection (defined as a urinary infection that occurred at least 48h post admission in the hospital)
- Patients has received any dose of active antimicrobial therapy (an antibiotic to which the infecting bacterium is susceptible) in the last 48h (prior to enrolment) except ≤ 2 dose of gentamicin.
- Patients presenting another site of infection than urinary (except onset of bacteraemia from urinary tract origin) due to Gram negative bacteria.
- Patients needing concomitant antimicrobial therapy.
- Septic shock
- Children (up to 18 years old)
- Women who is pregnant, breastfeeding, or expecting to conceive at any time during the study (pregnancy test will be conducted for woman without menopause)
- Patients with any kind of urinary/bladder catheter (JJ ureteral probe, ...)
- Hypersensitivity to the active substance, to penicillins or to any other type of beta-lactam agent
- Chronically dialyzed patients
- Patients having a creatinine clearance < 30 mL/min
- Complete obstruction of the urinary tract
- Perinephretic or intrarenal abscesses
- Tutorship or curatorship patient
- Patient unable to give his consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Temocillin Temocillin Treatment duration with a minimum of 5 days administration of the study drug: Temocillin (Negaban®) 6g/day (2g/tid) and as monotherapy. Total antibiotic treatment between 10 and 14 days according to local guidelines (up to 21 days in immunosuppressed patients).
- Primary Outcome Measures
Name Time Method Microbiological efficacy at Test of Cure in patients microbiologically evaluable 7 days post end of Temocillin Treatment The microbiological efficacy will be assessed by quantitative urine culture and defined as follows:
* Eradication : \< 10\^3 CFU/mL of the baseline pathogen
* Persistence : ≥ 10\^3 CFU/ml of the baseline pathogen
* Superinfection : ≥ 10\^5 CFU/ml of another uropathogen during therapy
* New infection : ≥ 10\^5 CFU/ml of another uropathogen after therapy
* Relapse : eradication at TOC but ≥ 10\^3 CFU/mL of the baseline pathogen at FU Overall microbiological response will be determined as "unfavorable" if persistence or superinfection or new infection or relapse.
- Secondary Outcome Measures
Name Time Method Clinical efficacy in clinical evaluable group 3 weeks for end of Temocillin Treatment Each patient's response will be categorized as cure (resolution of all clinical symptoms), improvement (normalization of body temperature but persistence of either urinary syndrome or flank pain) or failure (persistence of baseline clinical symptoms or emergence of new symptoms related to UTI).
Development of resistance to temocillin during treatment 3 weeks for end of Temocillin Treatment The acquisition of resistance will be monitored in the central laboratory and is defined as an increase in MIC of at least 4 dilutions.
Microbiological efficacy 3 weeks for end of Temocillin Treatment The microbiological efficacy will be assessed by quantitative urine culture and defined as follows:
* Eradication : \< 10\^3 CFU/mL of the baseline pathogen
* Persistence : ≥ 10\^3 CFU/ml of the baseline pathogen
* Superinfection : ≥ 10\^5 CFU/ml of another uropathogen during therapy
* New infection : ≥ 10\^5 CFU/ml of another uropathogen after therapy
* Relapse : eradication at TOC but ≥ 10\^3 CFU/mL of the baseline pathogen at FU
Trial Locations
- Locations (19)
APHP - Avicenne Hospital
🇫🇷Bobigny, France
APHP - Bicêtre Hospital
🇫🇷Kremlin-Bicêtre, France
APHP - St Louis
🇫🇷Paris, France
APHP - Bichat Hospital
🇫🇷Paris, France
CHU de Rouen
🇫🇷Rouen, France
CHU de Saint Etienne
🇫🇷Saint Etienne, France
APHP - Beaujon Hospital
🇫🇷Clichy, France
CHU de Martinique
🇫🇷Fort De France, France
CH de Perpignan
🇫🇷Perpignan, France
CHU de Nice
🇫🇷Nice, France
CH Ajaccio
🇫🇷Ajaccio, France
CH Annecy Genevois
🇫🇷Annecy, France
CHU de Pointe à Pitre
🇫🇷Pointe À Pitre, France
CHU de Poitiers
🇫🇷Poitiers, France
CHU de Tours
🇫🇷Tours, France
APHP - Cochin Hospital
🇫🇷Paris, France
CHU de Grenoble
🇫🇷Grenoble, France
CHU de Lille
🇫🇷Lille, France
CHU de Nantes
🇫🇷Nantes, France