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

Urinary Tract Infections Clinical Trial

— TEMO-ESBL  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02681263
• Other study ID #: 38RC15.213
• Secondary ID: 2015-004178-14
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: April 2016
• Est. completion date: September 2018

Study information

• Verified date: June 2018
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: September 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Urinary Tract Infections

Intervention

Drug:
• Temocillin
Treatment duration with a minimum of 5 days administration of the study drug: Temocillin (Negaban®) 6g/day (2g/tid) and as monotherapy.

Locations

Country	Name	City	State
France	CH Ajaccio	Ajaccio
France	CH Annecy Genevois	Annecy
France	APHP - Avicenne Hospital	Bobigny
France	APHP - Beaujon Hospital	Clichy
France	CHU de Martinique	Fort De France
France	CHU de Grenoble	Grenoble
France	APHP - Bicêtre Hospital	Kremlin-Bicêtre
France	CHU de Lille	Lille
France	CHU de Nantes	Nantes
France	CHU de Nice	Nice
France	APHP - Bichat Hospital	Paris
France	APHP - Cochin Hospital	Paris
France	APHP - St Louis	Paris
France	CH de Perpignan	Perpignan
France	CHU de Pointe à Pitre	Pointe À Pitre
France	CHU de Poitiers	Poitiers
France	CHU de Rouen	Rouen
France	CHU de Saint Etienne	Saint Etienne
France	CHU de Tours	Tours

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	French National Network of Clinical Research in Infectious Diseases (RENARCI)

Country where clinical trial is conducted

France, 

References & Publications (5)

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 ß-lactamase-producing Enterobacteriaceae. J Antimicrob Chemother. 2011 Nov;66(11):2628-31. doi: 10.1093/jac/dkr317. Epub 2011 Aug 2. — View 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. Epub 2007 Dec 10. — View Citation

Fournier D, Chirouze C, Leroy J, Cholley P, Talon D, Plésiat 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. — View 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. — View Citation

Schulze B, Heilmann HD. Treatment of severe infections with temocillin. Clinical and bacteriological evaluation. Drugs. 1985;29 Suppl 5:207-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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