Efficacy of 7 Days Versus 14 Days of Antibiotic Therapy for Acute Pyelonephritis in Kidney Transplant Recipients, a Multicentre Randomized Non-inferiority Trial. (SHORTCUT)

Assistance Publique - Hôpitaux de Paris

Status and phase

Enrolling

Phase 3

Conditions

Pyelonephritis Acute

Kidney Transplant Infection

Treatments

Drug: Usual antibiotic treatment

Drug: Short antibiotic treatment

Study type

Interventional

Funder types

Other

Identifiers

NCT05597540

APHP200020

Details and patient eligibility

About

Infections are a major cause of morbidity and mortality in solid organ transplant recipients. In kidney transplant recipients (KTR) urinary tract infection (UTI) represent 45-72% of all infections, and 30% of all hospitalizations for sepsis. Acute transplant pyelonephritis are the most common complications occurring in more than 20% of patients, mainly in the first year after transplantation. They are associated with an increased risk of acute kidney rejection and long-term kidney graft dysfunction. Gram-negative bacteria, mainly E. coli, account for more than 70% of UTI in KTR. As those infections are favoured by urinary tract modifications/defects and immunosuppression, they are often recurrent and necessitate repeated courses of antibiotics. Selective pressure due to antibiotic consumption, along with frequent hospital admissions and immunosuppression, are well known risk factors for the development of antibiotic resistant infections. Multidrug (MDR)- or extensively (XDR)- drug resistant Enterobacteriaceae including ESBL- or carbapenemase-producing organisms, are thus increasingly observed in transplant units and represent a global threat as very few new antibiotics are expected in the next decade.

One main strategy to limit antimicrobial resistance is to reduce the duration of antibiotic treatment. A 7 day-course is recommended for simple acute pyelonephritis (APN) treated with fluoroquinolones or parenteral B-lactams, prolonged up to 10 or 14 days in the presence of underlying disease at risk of complications. Most KT teams treat patients between 14-21 days as recommended by American guidelines. However, the need to extend treatment duration in immunosuppressed patients is a poorly defined concept and the optimal duration of treatment for APN in KTR is not known as these patients are excluded from most studies.

As there is an urgent need to reduce antibiotic consumption in this population at high risk of developing infections due to resistant pathogens, the hypothesis is that a 7 day-treatment is sufficient to cure APN with good clinical response after 48h of treatment in KTR and is as effective as 14 days.

Enrollment

470 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age >18 years KTR
APN defined by: fever (T°≥38°C) (with or without clinical signs and/or symptoms of UTI) and pyuria (≥10^4 white blood cells/mL or ≥10/mm3) and positive urine culture (uropathogen ≥10^3 CFU/mL susceptible to the empirically administrated antibiotic)
No confirmed or suspected febrile non urinary bacterial infection
No urologic/renal complication at baseline imaging (abscess, obstruction...)
Favourable early response to antibiotic treatment:48 to 60 hours after the first dose of antibiotic effective against the causative uropathogen) defined by: T°<38°C and improvement (or resolution) of signs and/or symptoms of urinary tract infection if present at diagnosis
Written informed consent

Exclusion criteria

Severe or complicated condition
- Any rapidly progressing disease or immediately life-threatening illness, including, but not limited to, septic shock, current or impeding respiratory failure, acute heart or liver failure
- Admission or stay in intensive care unit at baseline
- Obstruction of the urinary tract
- Renal, perinephric or prostatic abscess
Prior inclusion in this study
Current participation to another interventional study
Dual antibiotic therapy (prophylactic antibiotic such as cotrimoxazole allowed) (only 1 dose of aminoside is allowed before randomization)
First month post transplantation
Current indwelling catheter (including bladder catheter, ureteral stents, percutaneous nephrostomy tubes)
Neurogenic bladder
Enterocystoplasty
Immunodeficiency or immunosuppressive therapy not related to kidney transplantation including hematologic malignancy, cancer, asplenia, neutropenia<500 neutrophils/mm3
Pregnancy, breastfeeding
Hypersensitivity or previous severe adverse drug reaction to the antibiotic therapy
Unable or unwilling, in the judgment of the investigator, to comply with the protocol
Life expectancy<1 month
Patient under legal guardianship or without healthcare coverage
Homeless patient
Women with childbearing potential not using adequate contraception