Clinical trial NCT02681263: Efficacy of Temocillin in Urinary Tract Infection Due to ESBL Producing and AmpC Hyperproducing Enterobacteriaceae
Official title: Efficacy of Temocillin in Urinary Tract Infection Due to ESBL Producing and AmpC Hyperproducing Enterobacteriaceae
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Urinary Tract Infections
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: French National Network of Clinical Research in Infectious Diseases (RENARCI)
First posted: 2016-02-12
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Microbiological efficacy at Test of Cure in patients microbiologically evaluable
timeFrame: 7 days post end of Temocillin Treatment
Secondary outcomes:
measure: Clinical efficacy in clinical evaluable group
timeFrame: 3 weeks for end of Temocillin Treatment
measure: Microbiological efficacy
timeFrame: 3 weeks for end of Temocillin Treatment
measure: Development of resistance to temocillin during treatment
timeFrame: 3 weeks for end of Temocillin Treatment
Other outcomes:
Locations:
city: Ajaccio
country: France
facility: CH Ajaccio
city: Annecy
country: France
facility: CH Annecy Genevois
city: Bobigny
country: France
facility: APHP - Avicenne Hospital
city: Clichy
country: France
facility: APHP - Beaujon Hospital
city: Fort De France
country: France
facility: CHU de Martinique
city: Grenoble
country: France
facility: CHU de Grenoble
city: Kremlin-Bicêtre
country: France
facility: APHP - Bicêtre Hospital
city: Lille
country: France
facility: CHU de Lille
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: CHU de Nice
city: Paris
country: France
facility: APHP - Bichat Hospital
city: Paris
country: France
facility: APHP - Cochin Hospital
city: Paris
country: France
facility: APHP - St Louis
city: Perpignan
country: France
facility: CH de Perpignan
city: Pointe À Pitre
country: France
facility: CHU de Pointe à Pitre
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rouen
country: France
facility: CHU de Rouen
city: Saint Etienne
country: France
facility: CHU de Saint Etienne
city: Tours
country: France
facility: CHU de Tours
Study officials:
affiliation: University Hospital, Grenoble
name: Jean Paul STAHL, PU-PH
role: STUDY_CHAIR
References:
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.
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.
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.
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.
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.