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Efficacy of Temocillin in Urinary Tract Infection Due to ESBL Producing and AmpC Hyperproducing Enterobacteriaceae (TEMO-ESBL)

Primary Purpose

Urinary Tract Infections

Status
Unknown status
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Temocillin
Sponsored by
University Hospital, Grenoble
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urinary Tract Infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CH Ajaccio
  • CH Annecy Genevois
  • APHP - Avicenne Hospital
  • APHP - Beaujon Hospital
  • CHU de Martinique
  • CHU de Grenoble
  • APHP - Bicêtre Hospital
  • CHU de Lille
  • CHU de Nantes
  • CHU de Nice
  • APHP - Bichat Hospital
  • APHP - Cochin Hospital
  • APHP - St Louis
  • CH de Perpignan
  • CHU de Pointe à Pitre
  • CHU de Poitiers
  • CHU de Rouen
  • CHU de Saint Etienne
  • CHU de Tours

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temocillin

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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
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.

Full Information

First Posted
November 27, 2015
Last Updated
June 1, 2018
Sponsor
University Hospital, Grenoble
Collaborators
French National Network of Clinical Research in Infectious Diseases (RENARCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02681263
Brief Title
Efficacy of Temocillin in Urinary Tract Infection Due to ESBL Producing and AmpC Hyperproducing Enterobacteriaceae
Acronym
TEMO-ESBL
Official Title
Efficacy of Temocillin in Urinary Tract Infection Due to ESBL Producing and AmpC Hyperproducing Enterobacteriaceae
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Unknown status
Study Start Date
April 2016 (Actual)
Primary Completion Date
April 2018 (Actual)
Study Completion Date
September 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Grenoble
Collaborators
French National Network of Clinical Research in Infectious Diseases (RENARCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Tract Infections

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temocillin
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Temocillin
Other Intervention Name(s)
NEGABAN
Intervention Description
Treatment duration with a minimum of 5 days administration of the study drug: Temocillin (Negaban®) 6g/day (2g/tid) and as monotherapy.
Primary Outcome Measure Information:
Title
Microbiological efficacy at Test of Cure in patients microbiologically evaluable
Description
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.
Time Frame
7 days post end of Temocillin Treatment
Secondary Outcome Measure Information:
Title
Clinical efficacy in clinical evaluable group
Description
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).
Time Frame
3 weeks for end of Temocillin Treatment
Title
Microbiological efficacy
Description
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
Time Frame
3 weeks for end of Temocillin Treatment
Title
Development of resistance to temocillin during treatment
Description
The acquisition of resistance will be monitored in the central laboratory and is defined as an increase in MIC of at least 4 dilutions.
Time Frame
3 weeks for end of Temocillin Treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean Paul STAHL, PU-PH
Organizational Affiliation
University Hospital, Grenoble
Official's Role
Study Chair
Facility Information:
Facility Name
CH Ajaccio
City
Ajaccio
Country
France
Facility Name
CH Annecy Genevois
City
Annecy
Country
France
Facility Name
APHP - Avicenne Hospital
City
Bobigny
Country
France
Facility Name
APHP - Beaujon Hospital
City
Clichy
Country
France
Facility Name
CHU de Martinique
City
Fort De France
Country
France
Facility Name
CHU de Grenoble
City
Grenoble
Country
France
Facility Name
APHP - Bicêtre Hospital
City
Kremlin-Bicêtre
Country
France
Facility Name
CHU de Lille
City
Lille
Country
France
Facility Name
CHU de Nantes
City
Nantes
Country
France
Facility Name
CHU de Nice
City
Nice
Country
France
Facility Name
APHP - Bichat Hospital
City
Paris
Country
France
Facility Name
APHP - Cochin Hospital
City
Paris
Country
France
Facility Name
APHP - St Louis
City
Paris
Country
France
Facility Name
CH de Perpignan
City
Perpignan
Country
France
Facility Name
CHU de Pointe à Pitre
City
Pointe À Pitre
Country
France
Facility Name
CHU de Poitiers
City
Poitiers
Country
France
Facility Name
CHU de Rouen
City
Rouen
Country
France
Facility Name
CHU de Saint Etienne
City
Saint Etienne
Country
France
Facility Name
CHU de Tours
City
Tours
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
25433006
Citation
Laterre PF, Wittebole X, Van de Velde S, Muller AE, Mouton JW, Carryn S, Tulkens PM, Dugernier T. Temocillin (6 g daily) in critically ill patients: continuous infusion versus three times daily administration. J Antimicrob Chemother. 2015 Mar;70(3):891-8. doi: 10.1093/jac/dku465. Epub 2014 Nov 27.
Results Reference
background
PubMed Identifier
21810837
Citation
Balakrishnan I, Awad-El-Kariem FM, Aali A, Kumari P, Mulla R, Tan B, Brudney D, Ladenheim D, Ghazy A, Khan I, Virgincar N, Iyer S, Carryn S, Van de Velde S. Temocillin use in England: clinical and microbiological efficacies in infections caused by extended-spectrum and/or derepressed AmpC beta-lactamase-producing Enterobacteriaceae. J Antimicrob Chemother. 2011 Nov;66(11):2628-31. doi: 10.1093/jac/dkr317. Epub 2011 Aug 2.
Results Reference
background
PubMed Identifier
23433608
Citation
Fournier D, Chirouze C, Leroy J, Cholley P, Talon D, Plesiat P, Bertrand X. Alternatives to carbapenems in ESBL-producing Escherichia coli infections. Med Mal Infect. 2013 Feb;43(2):62-6. doi: 10.1016/j.medmal.2013.01.006. Epub 2013 Feb 19.
Results Reference
background
PubMed Identifier
4029026
Citation
Schulze B, Heilmann HD. Treatment of severe infections with temocillin. Clinical and bacteriological evaluation. Drugs. 1985;29 Suppl 5:207-9. doi: 10.2165/00003495-198500295-00046.
Results Reference
background
PubMed Identifier
18070831
Citation
De Jongh R, Hens R, Basma V, Mouton JW, Tulkens PM, Carryn S. Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection. J Antimicrob Chemother. 2008 Feb;61(2):382-8. doi: 10.1093/jac/dkm467. Epub 2007 Dec 10.
Results Reference
background

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

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