Pyelonephritis, Urinary Tract Infections
Conditions
Keywords
Pivmecillinam
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.
Interventions
DRUGpivmecillinam
Oral treatment of bacteremic pyelonephritis following standard initial parenteral treatment
Sponsors
University of Oslo
Sykehuset i Vestfold HF
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical efficacy | 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
| Measure | Time frame | Description |
|---|---|---|
| C-reactive protein-level (CRP) | Day 17 | Compare CRP-level on day 0 with day 17. |
| Readmission due to urinary tract infection (UTI) | Day 33 | Check if participants are readmitted due to UTI. |
| Readmission - any cause | Day 33 | Check if participants have been readmitted to hospital |
| Adverse effects | Day 33 | Registrate frequency of rash/skin problems, abdominal pain, clostridium difficile associated diarrhea |
| Microbial efficacy | Day 17 | Defined as \<1.000 CFU E.coli in urine |
Countries
Norway
Outcome results
None listed