Disturbance of the Intestinal Microbiota by Temocillin vs Cefotaxime in Treatment of Febrile Urinary Tract Infections

A Randomized, Controlled, Multicentre Trial of Collateral Damage on the Intestinal Microbiota Inferred by Temocillin Versus Cefotaxime in Patients Receiving Empirical Treatment for Febrile Urinary Tract Infections

Sponsors

Lead Sponsor: Håkan Hanberger

Source Public Health Agency of Sweden
Brief Summary

This study will evaluate the ecological impact on the intestinal microbiota and compare the safety and efficacy of temocillin compared to cefotaxime, in empiric treatment of febrile UTI. Half of participants will receive temocillin and the other half will receive cefotaxime.

Detailed Description

Temocillin is a narrow spectrum antibiotic with activity against gram negative bacteria inclusive many ESBL producing bacteria. Temocillin is approved and marketed in a few European countries since the 1980´s but not in Sweden. The aim of the study is to find an ecological favorable alternative to cephalosporins in the treatment of this common indication. The hypothesis is that treatment with temocillin causes less disturbances on the intestinal microbiota while at least comparable efficacy. The study will be performed as an open prospective multicentre study with two parallel groups comparing 2 g temocillin three times daily with 1-2 g cefotaxim three times daily for 7-10 days in male and female adult patients with febrile urinary tract infection.

Overall Status Completed
Start Date 2016-05-20
Completion Date 2019-08-01
Primary Completion Date 2019-08-01
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of patients with emergence of any of the two following events: Colonisation or infection with C. difficile and/or with Enterobacteriaceae resistant to 3rd generation cephalosporins. Measured in cultures from faecal samples. Within 12 hours after the last dose of study drug.
Secondary Outcome
Measure Time Frame
Number of patients with clinical cure in each treatment group. 7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
Number of patients with early clinical response. Within 12 hours after the 9th dose of study drug.
Bacteriological cure per patient and per pathogen measured as negative urine Culture <1000 CFU/ml. 7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
Early bacteriological response measured as negative urine Culture <1000 CFU/ml. Within 12 hours after the 9th dose of study drug.
Rate of patients with diarrhea (≥ 3 loose stools per day) From the first dose of study drug until 7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
Enrollment 157
Condition
Intervention

Intervention Type: Drug

Intervention Name: Temocillin

Description: Total antibiotic treatment 7-10 days, of which at least 72 hours (9 doses) initial temocillin administration. In case of bacteraemia at baseline the total antibiotic treatment can be extended up to 14 days.

Arm Group Label: Temocillin

Other Name: Negaban

Intervention Type: Drug

Intervention Name: Cefotaxime

Description: Total antibiotic treatment 7-10 days, of which at least 72 hours (9 doses) initial cefotaxime administration. In case of bacteraemia at baseline the total antibiotic treatment can be extended up to 14 days.

Arm Group Label: Cefotaxime

Other Name: Claforan

Eligibility

Criteria:

Inclusion Criteria: - Males and females ≥ 18 years of age with suspected or confirmed febrile UTI, fulfilling at least one of the following signs and symptoms: - Flank pain or suprapubic pain, Tenderness over the kidney on physical examination, Urinary symptoms such as dysuria, urinary frequency or urinary urgency - Fever ≥ 38.0°C (highest temperature recorded at home or at the hospital) - Positive urinalysis tests (U-Nitrit and/or U-LPK) - Have a pre-treatment baseline urinary culture obtained - Require iv antibacterial treatment of the presumed infection - Fertile women: Agree to practice highly effective anti-contraceptive methods from study-start to TOC - Signed informed consent Exclusion Criteria: - Have a documented history of hypersensitivity or allergic reaction to any beta-lactam - Pregnant or nursing women - Receipt of any prior potentially therapeutic antibacterial agent within 1 month before randomisation and sampling for urine and faecal cultures. Exceptions will prior treatment with pivmecillinam or nitrofurantoin. - Known chronic renal insufficiency (creatinine clearance < 10 mL/min at screening as estimated by Cockcroft-Gault), or receiving intermittent haemodialysis or peritoneal dialysis - Known colonization with ESBL - Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the subject or the quality of study data.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Håkan Hanberger, Professor Principal Investigator University Hospital, Linkoeping
Location
Facility:
Karolinska University Hospital | Solna, Stockholm, 171 76, Sweden
Helsingborg Hospital | Helsingborg, 251 87, Sweden
Centralsjukhuset Kristianstad | Kristianstad, 291 85, Sweden
Linköping University Hospital | Linköping, 581 85, Sweden
Skåne University Hospital | Lund, 221 85, Sweden
Vrinnevisjukhuset i Norrköping | Norrköping, 601 82, Sweden
Capio S:t Görans hospital | Stockholm, 112 81, Sweden
Sundsvall Hospital | Sundsvall, 856 43, Sweden
University Hospital of Umeå | Umeå, 901 85, Sweden
Västmanlands sjukhus i Västerås | Västerås, 721 89, Sweden
Örebro University Hospital | Örebro, 701 85, Sweden
Östersund Hospital | Östersund, 83131, Sweden
Location Countries

Sweden

Verification Date

2019-09-01

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Public Health Agency of Sweden

Investigator Full Name: Håkan Hanberger

Investigator Title: Professor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Temocillin

Type: Experimental

Description: Temocillin powder for solution för injection/infusion, per day 6 g (2 g three times per day). Treatment length 7-10 days of which at least 3 days administration with the study drug.

Label: Cefotaxime

Type: Active Comparator

Description: Cefotaxime powder for solution för injection/infusion, per day 3-6 g (1-2 g three times per day). Treatment length 7-10 days of which at least 3 days administration with the study drug.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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