Treating Pyelonephritis an Urosepsis With Pivmecillinam

Overview

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.

Full Title of Study: “The Efficacy and Safety of Pivmecillinam in Treating Bacteriemic Urosepsis Caused by E.Coli”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 21, 2020

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.

Interventions

  • Drug: pivmecillinam
    • Oral treatment of bacteremic pyelonephritis following standard initial parenteral treatment

Arms, Groups and Cohorts

  • Experimental: Pivmecillinam
    • Patients treated with pivmecillinam

Clinical Trial Outcome Measures

Primary Measures

  • Clinical efficacy
    • Time Frame: Day 17
    • Defined as abscence of fever, no need for other antibiotics than prescribed and improvement of symptoms (self-reported improvement and EQ 5D VAS-scale).

Secondary Measures

  • C-reactive protein-level (CRP)
    • Time Frame: Day 17
    • Compare CRP-level on day 0 with day 17.
  • Readmission due to urinary tract infection (UTI)
    • Time Frame: Day 33
    • Check if participants are readmitted due to UTI.
  • Readmission – any cause
    • Time Frame: Day 33
    • Check if participants have been readmitted to hospital
  • Adverse effects
    • Time Frame: Day 33
    • Registrate frequency of rash/skin problems, abdominal pain, clostridium difficile associated diarrhea
  • Microbial efficacy
    • Time Frame: Day 17
    • Defined as <1.000 CFU E.coli in urine

Participating in This Clinical Trial

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 Eligibility: All

Minimum Age: 18 Years

Maximum Age: 110 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sykehuset i Vestfold HF
  • Collaborator
    • University of Oslo
  • Provider of Information About this Clinical Study
    • Principal Investigator: Tore Stenstad, MD, PhD – Sykehuset i Vestfold HF
  • Overall Official(s)
    • Tore Stenstad, MD, PhD, Principal Investigator, The Hospital of Vestfold

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