Efficacy of Temocillin in Urinary Tract Infection Due to ESBL Producing and AmpC Hyperproducing Enterobacteriaceae

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy of Temocillin in Urinary Tract Infection Due to ESBL Producing and AmpC Hyperproducing Enterobacteriaceae

Conditions
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Urinary Tract Infections

Intervention / Treatment
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* Drug: Temocillin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temocillin<br>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). | Drug: Temocillin<br>* Treatment duration with a minimum of 5 days administration of the study drug: Temocillin (Negaban®) 6g/day (2g/tid) and as monotherapy.<br>* Other names: NEGABAN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiological efficacy at Test of Cure in patients microbiologically evaluable | 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. | 7 days post end of Temocillin Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy in clinical evaluable group | 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). | 3 weeks for end of Temocillin Treatment | 
| Microbiological efficacy | 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 | 3 weeks for end of Temocillin Treatment | 
| Development of resistance to temocillin during 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. | 3 weeks for end of Temocillin Treatment |