Keywords: -Fosfomycin -Urinary Tract Infection -Enterobacteriaceae -Antibiotic therapy
Conditions
Interventions
Treatment in the study arm consists of oral fosfomycin 3000mg every 24 hours.
Treatment in the standard of care arm consist of oral ciprofloxacin 500mg twice daily.
Both study and control arms will
Sponsors
University Medical Center, Utrecht
Eligibility
Inclusion criteria
Inclusion criteria: Hospitalised Competent women (≥18 years), able to give informed consent AF-UTI as presumptive diagnosis and primary reason for hospitalisation* Adequate intravenous antibiotic therapy for ≥48 - ≤120 hours** Candidate for safe iv to oral switch as judged by the attending physician Urine (≥10^4 CFU/ml) OR blood culture: Escherichia coli , ciprofloxacin S AND fosfomycin S*** * Acute Febrile Urinary Tract Infections (AF-UTI) are UTI with at least one of the forthcoming systemic signs or symptoms: fever or low temperature (≥38.0 C ͦ or <36 C ͦ), rigors, delirium, hemodynamic instability as a result of sepsis requiring intravenous fluids, increase in CRP (≥30mg/L) or leucocytes (≥12*109/L) AND at least one of the following local symptoms: lower abdominal pain, low back pain, flank pain or costo-vertebral angle pain or tenderness on physical examination, any of the following symptoms of UTI (dysuria, urinary urgency, urinary frequency, suprapubic/pelvic discomfort, macroscopic hematuria, new urinary incontinence or worsening of pre-existing incontinence). Local symptoms are not required if urine and blood culture yield phenotypically identical E.coli and UTI is the presumed source of infection according to the treating physician. The local study investigator determines the presumptive diagnosis as the primary reason for hospitalization with consultation of the attending physician. **Amoxicillin+/-clavulanic acid / 2nd or 3rd cephalosporin/ aminoglycoside/ carbapenem/ fluoroquinolones/ trimethoprim-sulfamethoxazole OR a combination AND in vitro susceptibility of the causative E.coli to at least one of the used agents *** If a participating microbiological laboratory only processes urine cultures ≥ 105 CFU/ml, only these will be included. If an urine or blood culture results in another non-E.coli bacteria that requires antibiotic treatment, the patient should be excluded. A patient is not eligible if non-E.coli-type Enterobacteriaceae are present in urine culture (≥103 CFU/ml) or blood culture.
Exclusion criteria
Exclusion criteria: Pregnant or nursing women Glomerular filtration rate < 30 ml/min/1,73 m2 or renal replacement therapy Concomitant systemic antibacterial treatment for another reason than AF-UTI including concomitant prophylactic antibacterial therapy # Ascertained or presumptive hypersensitivity to the active compounds and/or any excipient of the products or to any quinole Participation to any trial with an investigational product involved in the 30 days before the screening visit Every other laboratory result, clinical condition, disease or treatment that, in investigator’s opinion, make the subject non suitable for the study Specific comorbidity or diagnosis## Contraindications/interactions for any of the active compounds or medication ### Patients with inadequate understanding of the study risks or its requirements or unwilling to plan a follow-up visit # If prophylactic antibiotic therapy for UTI could not be paused during study therapy, the patient should be excluded ## Renal transplant patients, polycystic kidney disease, neutropenia (<500 /μl), paraplegia, urostomy, ileal loops, suspicion/presence of renal abscess, suspicion of septic metastatic foci/endocarditis, long-term urinary catheter (placed ≥24 hours before admission), e.g. double-J catheter, indwelling, nephrostomy catheter, suprapubic catheter. ### Concurrent use of Tizanidin, Clozapin or Theophyllin. If pausing or conversion of this medicine disadvantages the participant, she will be excluded. Patients with a history of tendon disease/disorder related to quinolone treatment. Patients with known risk factors for prolongation of the QT interval. Glucose-6-phosphate dehydrogenase deficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the cumulative incidence of survival and clinical cure (resolution of symptoms) 6-10 days post-treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints of the study include: 1. The cumulative incidence of microbiological cure 6-10 days post-treatment 2. The cumulative incidence of survival AND clinical cure (resolution of symptoms) AND microbiological cure 6-10 days post-treatment 3. The cumulative incidence of acquired fosfomycin resistance, ciprofloxacin resistance or ESBL-producing bacteria in urine culture 6-10 days post-treatment 4. The cumulative incidence of survival and clinical cure (resolution of symptoms) 30-35 days post-treatment 5. The cumulative incidence of mortality for any reason or related to UTI or study medicines within 30-35 days post-treatment 6. The cumulative incidence of ICU admissions for any reason or related to UTI or study medicines within 30-35 days post-treatment 7. The cumulative incidence of readmissions for any reason or related to UTI or study medicines within 30-35 days post-treatment 8. The cumulative incidence of relapses within 30-35 days post-treatment 9. The cumulative incidence of reinfections within 30-35 days post-treatment 10.The cumulative incidence of additional antibiotic use for UTI within 30-35 days post-treatment 11. The cumulative incidence of early discontinuation of study medicines because of adverse events OR because of loss of complaints 12. Total days of hospitalisation and Intensive Care Unit stay within 30-35 days post-treatment 13. The cumulative incidence of absenteeism within 30-35 days post-treatment 14. The cumulative incidence of study protocol related and unrelated adverse events, within 30-35 days post-treatment 15. Patient characteristics associated with the primary or secondary outcomes in both study arms (Charlson comorbidity index, Diabetes Mellitus y/n, indwelling catheter y/n, age </≥ 65 years, treatment restrictions at admission y/n, treatment restrictions at randomisation y/n, renal stones y/n) 16. Disease related characteristics associated with the primary or secondary outcome | — |
Contacts
Public ContactT. ten Doesschate
PO Box 85500, S.06.6.101
Outcome results
None listed