Effect of oral fosfomycin as a step-down treatment for complicated urinary tract infections induced by ESBL-producing enterobacteriaceae

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

1. Male or Female, >18 years of age

2. Patients whose complicated urinary tract infection status is expected to require hospitalization and administration of parenteral antibiotics according to the judgment of the physician

3. Patients with definitive or suspected complicated urinary tract infection

- Patients with showing 2 or more symptoms or signs related to urinary tract infection of 1) and 2)

1) Chills, myalgia and febrile sense are present along with fever
; Fever observed and documented by the healthcare provider within 24 hours of screening (oral, tympanic, rectal temperature > 38°C)
2) dysuria, frequency, urgency, suprapubic pain or pelvic pain
3) there is evidence of pyuria or bacteriuria
- a. pyuria; Leukocyte esterase + or >8-10 WBC/HPF in urinalysis
- b. bacteriuria; Nitrite + or >1 organism/oil-immersion field in urinalysis
(Female) >105/mL, 2 consecutive times, clean catch midstream urine
(Male) >105/mL, 1 time, clean catch midstream urine
(Male, Female) >102-103/mL, 1 time (Catheter urine or urine within 48hr after catheter removal)
4) A person who has one or more of the following risk factors
- Anatomical or functional abnormalities of the genitourinary system
- Underlying diseases (diabetes, renal failure, polycystic nephropathy, kidney transplant, immunocompromised, etc.)
- Catheter-associated infection
- Infection by drug resistant strains
- male
- Previous history of pyelonephritis
- Repeated antibiotic administration history
- Nosocomial infection

4. Patients who performed urine culture test (+/- blood culture test) at the time of screening

5. Patients whose pregnancy was excluded at the time of screening
- male
- A woman with a negative urine human chorionic gonadotropin (hCG) test

6. Pateitns who was removed of implanted urinary devices (e.g., nephrostomy tubes, ureteric stents, etc.) within 24 hours of randomization or before or before randomization

7. Patients meeting all of the following randomization criteria
7-1) Urine culture test (+/- blood culture test) at the time of screening, Fosfomycin sensitivity (minimum inhibitory concentration [MIC] =32 mg/L, Europena Committe) within 3-7 days of starting empirical treatment on Antimicrobial Susceptibility [EUCAST] criteria) in patients with ESBL-producing enterobacteria
7-2) Patients who meet the criteria for improvement as a result of clinical/laboratory tests 3-7 days after starting empirical treatment

* Criteria for improvement of clinical/laboratory test results (at least 3 of the following must be satisfied including ?)
? Stable vital signs (systolic blood pressure=100, pulse<100)
? subsided fever
? Improvement or disappearance of symptoms related to urinary tract infection
? Improvement trend or normalization of leukocyte and C-reactive protein levels
? As a result of urine analysis, the improvement of pyuria or negative
- Leukocyte esterase negative or WBC per HPF decrease or negative
? As a result of urine analysis, the trend of improvement in bacteriuria or negative
- negative conversion of nitrite
- Or, strains less than 105/mL in the middle urine, less than 102/mL strains in the urine when Foley catheter is inserted)

Exclusion Criteria

1. Patients with uncomplicated urinary tract infection
2. Patients with recent urinary tract or intrapelvic trauma
3. Those who have undergone urinary tract surgery within 7 days of randomization or planned urinary tract surgery during the study period
(Except for surgery or stent insertion or nephrostomy to relieve obstruction before the end of treatment)
4. Patients with complications of complicated urinary tract infection (eg, renal abscess, emphysema pyelonephritis, etc.) requiring treatment period of 10 days or more
5. Patients with non-renal co-infection such as endocarditis, osteomyelitis, meningitis, or pneumonia diagnosed within 7 days prior to randomization
6. Pregnant or breastfeeding women
7. Patients with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 5 times the upper limit of normal or total bilirubin more than twice the upper limit of normal at the time of screening
8. Patients with previous history of severe hypersensitivity or allergic reaction to Fosfomycin
9. Patients who, in the judgment of the healthcare provider, do not expect or do not agree to comply with the study protocol
10. Patients with other contraindications for oral fosfomycin administration
- Patients with severe renal failure (creatinine clearance less than 10mL/min)
- Hemodialysis patients
- There is a genetic problem such as fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency, so intake of sucrose should be restricted. patient

Study & Design

Study Type: Interventional Study

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Clinical improvement of complex urinary tract infection

Secondary Outcome Measures

Name	Time	Method
Microbiological improvement in urine samples (including blood samples when accompanied by bacteremia);Percentage of readmissions or emergency room/outpatient visits due to symptoms or signs associated with UTI;Duration until readmission or emergency room/outpatient revisit due to symptoms or signs associated with UTI;Improvement of symptoms and signs related to urinary tract infection;Incidence rate of Clostridium difficile-associated diarrhea