Temocillin Use in Complicated Urinary Tract Infections Due to Extended Spectrum Beta-Lactamases (ESBL)/AmpC Enterobacteriaceae

Study Overview
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Brief Summary
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This study is aimed at demonstrating the efficacy of temocillin in the treatment of complicated Urinary Tract Infection (UTI) due to confirmed Extended Spectrum Beta-Lactamases (ESBL) producing or AmpC hyperproducing Enterobacteriaceae in the United Kingdom.

Detailed Description
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The spectrum of activity together with the route of excretion of temocillin makes it a good candidate for the treatment of urinary tract infections. Several studies have shown very good clinical and microbiological activity in uncomplicated and complicated cystitis and pyelonephritis in adults and in pyelonephritis in children older than 2 months. However there is no specific study performed on Urinary Tract Infections due to broad spectrum ß-lactamases producing strains. In this context, this study is aimed at demonstrating the efficacy of temocillin in the treatment of complicated Urinary Tract Infection due to confirmed Extended Spectrum Beta-Lactamases (ESBL) producing or AmpC hyperproducing Enterobacteriaceae in the United Kingdom. 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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Temocillin Use in Complicated Urinary Tract Infections Due to Extended Spectrum Beta-Lactamases (ESBL) Producing and AmpC Hyperproducing Enterobacteriaceae in United Kingdom

Conditions
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Urinary Tract Infection

Intervention / Treatment
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* Drug: Temocillin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients presenting a complicated urinary tract infection due to a confirmed Extended Spectrum Beta-Lactamases (ESBL) producing or AmpC hyperproducing Enterobacteriaceae susceptible to temocillin requiring parenteral antimicrobial therapy. community or hospital acquired infecting bacteria. signed informed consent Exclusion Criteria: patients infected with a strain resistant to temocillin patients having received an active antimicrobial therapy during the 48h before the beginning of temocillin treatment except temocillin patients presenting another site of infection than urinary (except onset of bacteremia from urinary tract origin) due to Gram negative bacteria patients needing concomitant antimicrobial therapy with the exception of benzylpenicillin uncomplicated cystitis complete obstruction of the urinary tract prostatitis peri-nephretic or intrarenal abscesses renal transplant children (up to 18 years old) pregnancy or lactation chronically dialyzed patients immunocompromising therapy or illness known allergy to penicillin

Ages Eligible for Study
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Minimum Age: 21 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 group | Drug: Temocillin<br>* Antibiotic treatment<br>* Other names: Negaban;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiological cure | Eradication : < 10,000 Colony forming Unit/mL (CFU/mL) of the baseline pathogen Persistence : = 10,000 CFU/mL of the baseline pathogen Persistence with acquisition of resistance Superinfection : = 100,000 CFU/mL of another uropathogen during therapy New infection : = 100,000 CFU/mL of another uropathogen after therapy Relapse : eradication at end of treatment but = 10,000 CFU/mL of the baseline pathogen at follow up Relapse with acquisition of resistance | End of treatment (minimum 5 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical cure | Clinical status of the patient will be classified as cured (resolution of all clinical symptoms) improved failure (persistence of baseline clinical symptoms or emergence of new symptoms) | End of treatment (minimum 5 days) | 
| Development of resistance during treatment | Acquisition of resistance to temocillin during treatment on a microbiological point of view | End of treatment (minimum 5 days) | 
| Infection relapses monitored over 4-6 weeks | Relapse : eradication at end of treatment but = 10,000 CFU/mL of the baseline pathogen at follow up Relapse with acquisition of resistance | End of follow-up (up to 6 weeks) | 
| Monitoring of AE | Record of any untoward medical occurrence in a clinical trial patient administered temocillin and which does not necessarily have to have a causal relationship with the treatment. | From day 0 to up to 6 weeks | 
| ESBL & AmpC fecal carriage (optional) | All isolates of included patients will be kept frozen at -80°C and sent to the central laboratory for ESBL/AmpC confirmation and typing through molecular techniques. Pulse field gel electrophoresis will be performed on isolates from the same species for determination of clonality. | Start and end of treatment (minimum 5 days) | 
| Incidence of C. difficile infection | Clostridium difficile infection (CDI) is defined as recommended by the HPA Steering Group on Healthcare Associated Infection 35 : one episode of diarrhoea, defined either as stool loose enough to take the shape of a container used to sample it, or as Bristol Stool Chart types 5-7, which is not attributable to any other cause including medicines which occurs at the same time as a positive toxin assay (with or without a positive C. difficile culture) and/or endoscopic evidence of pseudomembranous colitis. | From day 0 to up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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UTI, ESBL, AmpC Enterobacteriaceae