Clinical trial NCT03282006: Treating Pyelonephritis an Urosepsis With Pivmecillinam
Official title: The Efficacy and Safety of Pivmecillinam in Treating Bacteriemic Urosepsis Caused by E.Coli
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pyelonephritis
Urinary Tract Infections
Keywords: Pivmecillinam
Lead sponsor: Sykehuset i Vestfold HF
Sponsor class: OTHER
Collaborators: name: University of Oslo
First posted: 2017-09-13
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Clinical efficacy
timeFrame: Day 17
Secondary outcomes:
measure: C-reactive protein-level (CRP)
timeFrame: Day 17
measure: Readmission due to urinary tract infection (UTI)
timeFrame: Day 33
measure: Readmission - any cause
timeFrame: Day 33
measure: Adverse effects
timeFrame: Day 33
measure: Microbial efficacy
timeFrame: Day 17
Other outcomes:
Locations:
city: Tønsberg
country: Norway
facility: Vestfold Hospital Trust
state: Vestfold
Study officials:
affiliation: The Hospital of Vestfold
name: Tore Stenstad, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hansen BA, Grude N, Lindbaek 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.