The incidence of renal scarring did not differ significantly in children with acute pyelonephritis and scintigraphy-documented acute lesions who were treated with oral antibiotics, compared with those treated with sequential intravenous and oral antibiotics in a prospective multicenter trial.
Although the trial wasn’t statistically powered to demonstrate noninferiority of oral treatment, compared with sequential intravenous/oral treatment, the findings confirm those of prior studies and support the use of oral antibiotics for primary acute pyelonephritis (APN) in this population, Dr. Nathalie Bocquet of Assistance Publique-Hôpitaux de Paris and her colleagues reported Jan. 30 in Pediatrics.
In 85 children randomized to receive treatment with oral antibiotics and in 86 randomized to receive sequential treatment with intravenous and oral antibiotics, the incidence of renal scarring based on per protocol analysis was 30.8% and 27.3%, respectively, the investigators said (Pediatrics 2012;129:e269-75).
Participants were infants and children aged 1-36 months who presented with a first case of febrile urinary tract infection (UTI) between August 2004 and April 2008 and who were found to have renal involvement based on serum procalcitonin measurement. All had normal ultrasound findings prenatally, no known uropathy, and no suspected uropathy after ultrasound examination at study inclusion. Dimercaptosuccinic acid (DMSA) scintigraphy was performed within 8 days of inclusion, and those found to have acute lesions underwent follow-up and scintigraphy 6-8 months later.
Treatment for those in the oral antibiotics group included 10 days of cefixime, consisting of an initial double dose of 8 mg/kg administered in the emergency department, followed by 4 mg/kg twice daily. Those in the sequential treatment group received 50 mg/kg of IV ceftriaxone for 4 days followed by oral cefixime at a dose of 4 mg/kg twice daily for 6 days.
After the initial 10-day treatment, antibiotic prophylaxis with co-trimoxazole or another antibiotic adapted to prevent bacterial resistance was continued for up to 1 month until voiding cystography (VCG) could be performed; prophylaxis was discontinued if the VCG findings were normal.
"The frequencies of renal scarring in our treatment groups are comparable with those of previous trials, which reported renal scarring frequencies of 15%-20% and 45%-60%," the investigators noted.
Because high serum procalcitonin concentrations have been shown in prior studies to correlate with acute renal defects on DMSA scintigraphy, they used serum procalcitonin to identify children at high risk for renal involvement.
"Because one of our inclusion criteria was a PCT [procalcitonin] greater than or equal to 0.5 ng/mL, 85.4% of the patients in our study had positive acute phase scintigraphies," they said, noting that in the prior studies, the rates ranged from 60.5% to 63.3%.
"Consistent with what has been previously reported, we found that serum PCT concentrations were significantly higher in children who developed scars than in those who had acute abnormalities but no definitive damage. For this reason, monitoring PCT levels in children afflicted with APN could help to identify those at risk for renal complications even in the absence of a suspected or documented uropathy," they said.
Additionally, they noted that all pathogens isolated in this study were Escherichia coli, which is usually the main pathogen isolated in UTI.
"Antimicrobial treatment with cefixime is a safe choice as long as the likelihood of infection with an E. coli strain that is resistant to third-generation cephalosporins remains low," they said, adding: "Our results support the use of a completely oral cefixime treatment for initial episodes of APN involving a gram-negative bacteria strain in infants and children aged 1 month to 3 years who are without urological abnormalities and without clinical hemodynamic impairment."
This approach to treatment can be proposed for children with serum PCT concentrations greater than 0.5 ng/mL who are at high risk for renal involvement, as well as for those with lower PCT concentrations, despite their low risk for acute renal involvement, they said.
"Oral treatment can facilitate outpatient management of young children with APN because it reduces cost, familial disruption, and nosocomial disease exposure," they concluded.
This study was supported by the Ministry of Health, the Direction de la Recherche Clinique, and the Unit of Clinical Research in Hospital Necker. Only one of the study authors, Dr. Vincent Gajdos, had disclosures to report: He has received consulting fees from GlaxoSmithKline.