Treating Pyelonephritis an Urosepsis With Pivmecillinam (MePUr)

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

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.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections; Pyelonephritis
• Intervention / Treatment: Drug: pivmecillinam

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.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Vestfold
    • Tønsberg, Vestfold, Norway, 3103
      • Vestfold Hospital Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 110 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pivmecillinam; Patients treated with pivmecillinam	Drug: pivmecillinam; Oral treatment of bacteremic pyelonephritis following standard initial parenteral treatment; Other Names: Selexid, Penomax

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sykehuset i Vestfold HF
• Collaborators: University of Oslo
• Investigators: Principal Investigator: Tore Stenstad, MD, PhD, The Hospital of Vestfold

Publications and helpful links

General Publications

• Hansen BÅ, Grude N, Lindbæk M, Stenstad T. The efficacy of pivmecillinam in oral step-down treatment in hospitalised patients with E. coli bacteremic urinary tract infection; a single-arm, uncontrolled treatment study. BMC Infect Dis. 2022 May 19;22(1):478. doi: 10.1186/s12879-022-07463-7.

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2017
• Primary Completion (Actual): April 21, 2020
• Study Completion (Actual): April 21, 2020

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (Actual): September 13, 2017

Study Record Updates

• Last Update Posted (Actual): April 22, 2020
• Last Update Submitted That Met QC Criteria: April 21, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Pivmecillinam
• Additional Relevant MeSH Terms: Infections; Kidney Diseases; Urologic Diseases; Nephritis; Nephritis, Interstitial; Pyelitis; Urinary Tract Infections; Pyelonephritis; Anti-Infective Agents; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Renal Agents; Amdinocillin Pivoxil
• Other Study ID Numbers: 2016-000984-18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No