Longer treatment with intravenous antibiotics does not decrease rate of renal scarring in children with pyelonephritis

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• Bouissou F, Munzer C, Decramer S, Roussel B, Novo R, Morin D, et al., on behalf of the French Society of Nuclear Medicine and Molecular Imaging. Prospective, randomized trial comparing short and long intravenous antibiotic treatment of acute pyelonephritis in children: dimercaptosuccinic acid scintigraphic evaluation at 9 months. Pediatrics 2008;121:e553-60
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Bouissou F, Munzer C, Decramer S, Roussel B, Novo R, Morin D, et al., on behalf of the French Society of Nuclear Medicine and Molecular Imaging. Prospective, randomized trial comparing short and long intravenous antibiotic treatment of acute pyelonephritis in children: dimercaptosuccinic acid scintigraphic evaluation at 9 months. Pediatrics 2008;121:e553-60 

Question Among children with pyelonephritis, is there a difference in the incidence of renal scarring at 6 to 9 months in those treated with 3 days versus 8 days of ceftriaxone?

Design Prospective, randomized, multicenter trial.

Setting Multiple hospitals in France.

Participants A total of 548 children were randomized; 48 were secondarily excluded, and 117 were lost to follow-up, leaving a cohort of 383 children (median age = 15 months) with a first episode of acute pyelonephritis.

Intervention All patients received 2 days of netilmicin (7 mg/kg) and then 3 days of ceftriaxone (50 mg/kg). They were then randomized to either 5 days of oral antibiotics (short intravenous treatment, n = 205) or 5 days of intravenous ceftriaxone (long intravenous treatment, n = 178).

Outcomes Incidence of renal scarring on 99m technetium-dimercaptosuccinic acid scintigraphy scanning at 6 to 9 months of follow-up.

Main Results At inclusion, median duration of fever was 43 hours, and median C-reactive protein level was 122 mg/L. A total of 37% (143 of 383) of patients had vesicoureteral reflux grades 1 to 3. Patient characteristics at inclusion were similar in both groups, except for a significantly higher proportion of girls in the short intravenous treatment group. The frequency of renal scars at scintigraphy was similar in both groups. Multivariate analysis demonstrated that renal scars were significantly associated with increased renal height at initial ultrasound scanning and with the presence of grade 3 vesicoureteral reflux.

Conclusions The incidence of renal scars was similar in patients who received 3 days compared with 8 days of intravenous ceftriaxone. Increased renal height at initial ultrasound examination and grade 3 vesicoureteral reflux were significant risk factors for renal scars.

Commentary This study randomizes children alleged to be having their first episode of presumed acute pyelonephritis (age range 3 months to 16 years) to receive either short-term intravenous antibiotics (3 days followed by a nonstandardized oral regimen for an additional 5 days) versus long-term intravenous antibiotics (8 days of ceftriaxone). By including children up to 16 years of age, there is a substantial risk that some of these subjects have had previous, perhaps unrecognized, episodes of urinary tract infection or acute pyelonephritis. Furthermore, their measure of presumed acute pyelonephritis is a febrile urinary tract infection with an elevated C-reactive protein. Although these are reasonable clinical criteria for acute pyelonephritis, a baseline 99m technetium-dimercaptosuccinic acid scintigraphy scan, which might have demonstrated parenchymal involvement or evidence of preexisting scars, was not performed. The protocol allowed urine collection either by bag (unfortunately) or by clean catch. Accordingly, some patients may not have had a bona fide urinary tract infection. Surprisingly, the authors chose to treat patients parenterally with 2 drugs, although there is little justification for adding any drug to an advanced generation cephalosporin, which is quite comprehensive in its activity against Gram-negative urinary tract pathogens. There is a very substantial drop out rate (nearly 25%), which prompts concern that patients who may not have done well discontinued participation prematurely. Furthermore, they excluded children deemed to be severely ill. This does not seem reasonable, because all children in the study received at least 3 days of parenteral therapy, and none received placebo. Ultimately, they showed that the incidence of renal scars was comparable in both groups of children. These results are similar to those reported in a younger and sicker group of patients when intravenous cefotaxime was compared with an entirely oral course of treatment with cefixime.¹ Accordingly, the investigation by Bouissou et al strongly supports abbreviated courses of parenteral antimicrobials in children with acute pyelonephritis.

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Reference 

1. Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, Majd M, et al. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics. 1999;104:127–129
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