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

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.

Inclusion Criteria:Age >18 years KTRAPN defined by: fever (T°≥38°C) (with or without clinical signs and/or symptoms of UTI) and pyuria (≥10.4 white blood cells/mL) and positive urine culture (single uropathogen ≥10.3 CFU/mL susceptible to the empirically administrated antibiotic)No confirmed or suspected febrile non urinary bacterial infectionNo urologic/renal complication at baseline imaging (abscess, obstruction...)Early response after 48h of antibiotic treatment defined by: T°<38°C and improvement or complete resolution of any symptoms and/or signs of UTI if present at baseline 48 to 60 hours after the first administration of effective antibiotic.Written informed consentExclusion Criteria:Severe or complicated conditionsAny rapidly progressing disease or immediately life-threatening illness, including, but not limited to, septic shock, current or impeding respiratory failure, acute heart or liver failureAdmission or stay in intensive care unit at baselineObstruction of the urinary tractRenal, perinephric or prostatic abscessDual antibiotic therapy (prophylactic antibiotic such as cotrimoxazole allowed) (only 1 dose of aminoside is allowed before randomization)First month post transplantationCurrent indwelling catheter (including bladder catheter, ureteral stents, percutaneous nephrostomy tubes)Prior inclusion in this studycurrent participation to another interventional studyNeurogenic bladderEnterocystoplastyImmunodeficiency or immunosuppressive therapy not related to kidney transplantation including hematologic malignancy, cancer, asplenia, neutropenia<500 PNN/mm3Pregnancy, breastfeedingHypersensitivity or previous severe adverse drug reaction to the antibiotic therapyUnable or unwilling, in the judgment of the investigator, to comply with the protocolLife expectancy<1 monthPatient under legal guardianship or without healthcare coverageHomeless patient