evaluation of the effectiveness of antibiotic prophylaxis in children with a previous urinary tract infection

Conditions: Urinary Tract Infections

Summary: our hypothesis is that long-term antimicrobial prophylaxis does not reduce the recurrence of infection and the risk of appearance of kidney scars in children with a documented previous upper uti.

background upper urinary tract infections (uti) are common in children, especially when functional and anatomical abnormalities of the urinary tract co-exist, such as vesico-ureteral reflux (vur), urinary tract obstruction uropathy and bladder dysfunction. they are associated with the risk of long-term complications, including permanent renal damage (renal scarring), which occurs in 15% of cases. the objective of the diagnosis and medical treatment of uti in children is the prevention of such complications. medical treatment includes long-term antimicrobial prophylaxis to be continued for periods ranging from 6 months to 2 years. recent studies have revealed the emergence of therapy-induced resistance. a review of the literature has highlighted the lack of properly designed, large clinical trials, demonstrating the efficacy of long-term low-dose antimicrobial prophylaxis in terms of reduction in uti recurrence. methods and design the study is a controlled, randomised, open-label, 3-armed, parallel-group clinical trial comparing no prophylaxis (group 1) with prophylaxis with co-trimoxazole 15 mg/kg daily (group 2) and with amoxicillin + clavulanic acid 15 mg/kg daily (group 3) for 12 months. assuming that the incidence of recurrences is 20%, defining efficacy as an incidence of 10% per group and setting  error = 0.05 and power = 90%, 220 patients per group (i.e. a total of 660 patients) are required the study population will consist of children aged between 2 months and 6 years, with normal renal function (creatinine clearance  70 ml/min/1.73m2) and a first episode of documented uti, who presents at least one of the following: an acute pyelonephritic lesion at the dmsa scan and/or a vur at the baseline micturating cystography. patients will be followed-up for 12 months. urinalysis and urine cultures will be performed every month and clinical examinations after 6 and 12 months; both will be performed whenever uti is suspected. sonography, doppler sonography (optional) and dmsa scintigraphy will be performed at baseline and at the end of the study.

Eligibility criteria:
inclusion criteria: * age between 2 months and 6 years * creatinine clearance (calculated according to schwartz)  70 ml/min/1.73 m2 (for children in their first year of life, serum creatinine levels within normal range for age and sex) * first documented upper uti (diagnostic criteria in table 1) * imaging diagnostic work-up completed (table 2) with at least the presence of an acute lesion at the dmsa scan and or a primary non severe reflux ( 1st or 3rd degree) * informed consent of parents exclusion criteria: * patients with chronic renal insufficiency or  30% relative function of one kidney at dmsa scan * patients with urinary tract disorders, such as vesico-ureteral reflux due to complex malformations of the urinary tract, obstruction of the posterior urethra, ureterocele or single kidney, neurogenic bladder * patients with reflux  4th degree * patients with pyelonephritis that developed during prophylaxis instituted because of prenatal diagnosis of urinary tract dilatation  hypersensitivity to one of the two selected antimicrobial agents

Keywords: urinary tract infections children antibiotic prophylaxis renal scintigraphy vesico ureteral reflux