Treating Pyelonephritis an Urosepsis With Pivmecillinam

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Pyelonephritis, Urinary Tract Infections

Intervention / Treatment
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* Drug: pivmecillinam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 110 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pivmecillinam<br>Patients treated with pivmecillinam | Drug: pivmecillinam<br>* Oral treatment of bacteremic pyelonephritis following standard initial parenteral treatment<br>* Other names: Selexid, Penomax;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pivmecillinam