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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 7 day-duration antibiotic treatment | Experimental |
| |
| 14 day-duration antibiotic treatment | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Short antibiotic treatment | Drug | 7 day-duration antibiotic treatment. The choice of antibiotic treatment is left to the medical team in charge of the patient. |
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| Measure | Description | Time Frame |
|---|---|---|
| Clinical cure day 30 | Clinical cure and no additional antibiotic treatment since the end of antibiotic treatment up to the main evaluation at day 30. Clinical cure is defined as fever <38°C and no symptoms of Urinary Tract Infection (UTI). | at day 30 |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical cure day 90 | Clinical cure and no additional antibiotic treatment since the end of antibiotic treatment up to the main evaluation at day 90. Clinical cure is defined as fever <38°C and no symptoms of Urinary Tract Infection (UTI). | at day 90 |
| Clinical cure day 180 |
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Inclusion Criteria:
Exclusion Criteria:
Severe or complicated condition
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
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Matthieu Lafaurie, MD | Contact | 142494117 | +33 | matthieu.lafaurie@aphp.fr |
| Jérôme Lambert, Pr | Contact | 142499742 | +33 | jerome.lambert@u-paris.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Bordeaux | Not yet recruiting | Bordeaux | France |
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Randomized double blind trial
| Usual antibiotic treatment | Drug | 14 day-duration antibiotic treatment. The choice of antibiotic treatment is left to the medical team in charge of the patient. |
|
Clinical cure and no additional antibiotic treatment since the end of antibiotic treatment up to the main evaluation at day 180. Clinical cure is defined as fever <38°C and no symptoms of Urinary Tract Infection (UTI). |
| at day 180 |
| Microbiological cure day 30 | Microbiological cure is defined as a sterile urine or uropathogene ≤ 10.3 CFU/mL in urine culture | at day 30 |
| Microbiological cure day 90 | Microbiological cure is defined as a sterile urine or uropathogene ≤ 10.3 CFU/mL in urine culture | at day 90 |
| Microbiological cure day 180 | Microbiological cure is defined as a sterile urine or uropathogene ≤ 10.3 CFU/mL in urine culture | at day 180 |
| Incidence of relapse/recurrence day 30 | Relapse or recurrence of the Urinary Tract Infection | at day 30 |
| Incidence of relapse/recurrence day 90 | Relapse or recurrence of the Urinary Tract Infection | at day 90 |
| Incidence of adverse event | Incidence of adverse events imputable to antibiotic treatment | at day 180 |
| Kidney function | Evaluated by MDRD or CKD MDRD : Modification of Diet in Renal Disease (MDRD) Study equation. Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P. Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol 2005;16(3):763-73. CKD-EPI (Chronic Kidney Disease EPIdemiology collaboration, Levey, 2009) A New Equation to Estimate Glomerular Filtration Rate. Andrew S. Levey, MD; Lesley A. Stevens, MD, MS; Christopher H. Schmid, PhD; Yaping (Lucy) Zhang, MS; Alejandro F. Castro III, MPH; Harold I. Feldman, MD, MSCE; John W. Kusek, PhD; Paul Eggers, PhD; Frederick Van Lente, PhD; Tom Greene, PhD; and Josef Coresh, MD, PhD, MHS, for the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). Annals of Internal Medicine 2009;150(9):604-613 | at day 90 |
| Kidney function | Evaluated by MDRD or CKD MDRD : Modification of Diet in Renal Disease (MDRD) Study equation. Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P. Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol 2005;16(3):763-73. CKD-EPI (Chronic Kidney Disease EPIdemiology collaboration, Levey, 2009) A New Equation to Estimate Glomerular Filtration Rate. Andrew S. Levey, MD; Lesley A. Stevens, MD, MS; Christopher H. Schmid, PhD; Yaping (Lucy) Zhang, MS; Alejandro F. Castro III, MPH; Harold I. Feldman, MD, MSCE; John W. Kusek, PhD; Paul Eggers, PhD; Frederick Van Lente, PhD; Tom Greene, PhD; and Josef Coresh, MD, PhD, MHS, for the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). Annals of Internal Medicine 2009;150(9):604-613 | at day 180 |
| Hospital length of stay | Hospitalisation length stay defined by the delay between the date of inclusion and the date of hospital discharge | Up to day 180 |
| Antibiotic consumption | Antibiotic consumption (indication, dose and duration) throughout the follow-up will be recorded. | Up to day 180 |
| Rectal carriage | Rectal carriage of antibiotic resistant Enterobacteriaceae | at inclusion |
| Rectal carriage | Rectal carriage of antibiotic resistant Enterobacteriaceae | at day 30 |
| Hôpital Foch | Not yet recruiting | Boulogne-Billancourt | France |
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| CHU Mondor | Recruiting | Créteil | France |
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| CHU Lyon | Not yet recruiting | Lyon | France |
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| CHU Nantes | Recruiting | Nantes | France |
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| CHU Kremlin-Bicêtre | Not yet recruiting | Paris | France |
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| CHU Necker | Recruiting | Paris | France |
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| CHU Saint Louis | Recruiting | Paris | France |
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| CHU Toulouse | Not yet recruiting | Toulouse | France |
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