Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial

Abstract

Objective To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis. Design Multicentre, randomised controlled, open labelled, parallel group, non-inferiority trial. Setting 28 paediatric units in north east Italy. Participants 502 children aged 1 month to <7 years with clinical pyelonephritis. Intervention Oral co-amoxiclav (50 mg/kg/day in three doses for 10 days) or parenteral ceftriaxone (50 mg/kg/ day in a single parenteral dose) for three days, followed by oral co-amoxiclav (50 mg/kg/day in three divided doses for seven days). Main outcomes measures Primary outcome was the rate of renal scarring. Secondary measures of efficacy were time to defervescence (<37°C), reduction in inflammatory indices, and percentage with sterile urine after 72 hours. An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid (DMSA) scintigraphy within 10 days after study entry. Results Intention to treat analysis showed no significant differences between oral (n=244) and parenteral (n=258) treatment, both in the primary outcome (scarring scintigraphy at 12 months 27/197 (13.7%) v 36/203 (17.7%), difference in risk −4%, 95% confidence interval −11.1% to 3.1%) and secondary outcomes (time to defervescence 36.9 hours (SD 19.7) v 34.3 hours (SD 20), mean difference 2.6 (−0.9 to 6.0); white cell count 9.8×10 9 /l (SD 3.5) v 9.5×10 9 /l (SD 3.1), mean difference 0.3 (−0.3 to 0.9); percentage with sterile urine 185/186 v 203/204, risk difference −0.05% (−1.5% to 1.4%)). Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry.Conclusions Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children.

Randomised trial of oral versus sequential intravenous/oral cephalosporins in children with pyelonephritis

“…The proportions of renal scarring in patients (oral group: 26%; intravenous/oral group: 46%) were comparable with previous scintigraphy investigations that documented renal scarring in 29-60% of children after acute pyelonephritis [5,15,16,21,24,30,31,35]. These results indicate that mere oral ceftibuten therapy is as efficacious as parenteral therapy, i.e.…”

“…a 10-fold higher range, indicating more pronounced inflammation, which, in turn, may explain the higher rate of renal scarring. Also, Montini et al [21] reported an initial CRP concentration nine-fold above the upper normal value, with a similar range of scarring in children. Nevertheless, by bag urine collection, they may have included children with false-positive urine cultures, as urine collected by catheter was not a prerequisite for inclusion as in our study and the study by Hoberman et al [14].…”

“…In the study by Montini et al [21], amoxicillin/clavulanic acid was given for 10 days to 135 children aged 1 month to 7 years. Renal scarring developed in 26/96 patients (28%), with lesions on acutephase scintigraphy comparable to the 26% found among children with oral treatment in our study and in earlier studies [5,15,16,24,30,35].…”

“…pyelonephritis). Up to two thirds of children with acute pyelonephritis show a lesion (defect) on technetium99m-labelled dimercaptosuccinic acid (DMSA) scintigraphy during the acute phase [5,14,21,25]. Only these children develop post-infectious renal scarring and the incidence is 29-60% [5,15,21,24,30,35].…”

“…Thus, oral antimicrobial therapy of acute pyelonephritis appeared to be a safe option, particularly for children older than 6 months of age. Indeed, the results from two prior prospective trials suggested that acute pyelonephritis in children could be treated with oral antibiotics [14,21]. Two additional aspects need consideration.…”