Treating Pyelonephritis an Urosepsis With Pivmecillinam

The Efficacy and Safety of Pivmecillinam in Treating Bacteriemic Urosepsis Caused by E.Coli

Sponsors

Lead Sponsor: Sykehuset i Vestfold HF

Collaborator: University of Oslo

Source Sykehuset i Vestfold HF
Brief Summary

Febrile urinary tract infections and urosepsis are common and potentially serious infections that require effective antimicrobial treatment. The duration of parenteral treatment depends on oral alternatives. These alternatives are few and due to antimicrobial resistance, quinolones are "standard of care". The increased use of quinolones is concerning because of its negative ecological aspects and it is confirmed an increasing incidence of resistant E.coli to quinolones in Norwegian isolates. Pivmecillinam is an antibiotic with high susceptibility to E.coli but the evidence for treating febrile urinary tract infections is insufficient. This trial will investigate the efficacy and safety of pivmecillinam in treating pyelonephritis and urosepsis caused by E.coli. The hypothesis is that urosepsis can safely be treated with pivmecillinam when it is given after 2-3 days with empirical i.v. antibiotics.

Detailed Description

This trial will be conducted at Vestfold Hospital, Norway, and is a prospective observational study with intention to treat. Participants will be consecutively included among hospitalized patients suffering from urosepsis - see eligibility criteria. After 3 days with parenteral antibiotics, when clinical improvement and absence of fever/leukocytosis is confirmed, the participants will start on pivmecillinam 400mg four times daily and be discharged. Pivmecillinam is to be taken for one week. The participants will be contacted by phone on day 4, 10 and 33 (days after admission). On day 17 (test of cure, TOC) they will meet for physical examination. They will report symptom score (standardized schema) on day 0, and 17. Urine samples will be collected on day 10 and 17. Blood samples on day 17. All data will be stored anonymously. The trial will be monitored by extern resources.

Overall Status Completed
Start Date September 29, 2017
Completion Date April 21, 2020
Primary Completion Date April 21, 2020
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Clinical efficacy Day 17
Secondary Outcome
Measure Time Frame
C-reactive protein-level (CRP) Day 17
Readmission due to urinary tract infection (UTI) Day 33
Readmission - any cause Day 33
Adverse effects Day 33
Microbial efficacy Day 17
Enrollment 53
Condition
Intervention

Intervention Type: Drug

Intervention Name: pivmecillinam

Description: Oral treatment of bacteremic pyelonephritis following standard initial parenteral treatment

Arm Group Label: Pivmecillinam

Other Name: Selexid, Penomax

Eligibility

Criteria:

Inclusion Criteria: - E.coli in blood culture - AND identical isolate in urine sample (>= 1.000 CFU) OR relevant clinical signs of UTI Exclusion Criteria: - Bacterial infection origin from another organ (e.g. pneumonia) - Severe sepsis with multiorgan failure - Perinephritic abscess - Pyonephrosis requiring drainage - Allergy to pivmecillinam - E.coli isolate resistant to pivmecillinam - Pregnancy/breastfeeding - Severe neutropenia - Prostatitis - Severe kidney failure (eGFR<15 ml/min) - Using valproate

Gender: All

Minimum Age: 18 Years

Maximum Age: 110 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Tore Stenstad, MD, PhD Principal Investigator The Hospital of Vestfold
Location
Facility: Vestfold Hospital Trust
Location Countries

Norway

Verification Date

April 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Sykehuset i Vestfold HF

Investigator Full Name: Tore Stenstad

Investigator Title: MD, PhD

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Pivmecillinam

Type: Experimental

Description: Patients treated with pivmecillinam

Acronym MePUr
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov