Oral Antibiotics for Pyelonephritis in Children
Abstract & Commentary
By Hal B. Jenson, MD, FAAP, Chief Academic Officer, Baystate Health; Professor of Pediatrics and Dean of the Western Campus of Tufts University School of Medicine. Dr. Jenson is on the speaker's bureau for Merck.
This article originally appeared in the September 2007 issue of Infectious Disease Alert. It was edited by Stan Deresinski, MD, and peer reviewed by Connie Price, MD.
Synopsis: Treatment of the first episode of pyelonephritis in children with oral antibiotics alone for 10 days is not inferior to parenteral therapy for 3 days followed by oral therapy for 7 days.
Source: Montini G, et al. Antibiotic treatment for pyelonephritis in children: Multicentre randomised controlled non-inferiority trial. BMJ. 2007 July 4 [Epub ahead of print].
A multicenter, non-inferiority, open-labeled, randomized, controlled trial of oral amoxicillin-clavulanate (50 mg/kg/day divided 3 times a day for 10 days) compared to initial parenteral treatment with ceftriaxone (50 mg/kg/day as a single daily dose for 3 days) followed by oral amoxicillin-clavulanate (for 7 days) for children < 6 years of age with acute pyelonephritis and no anatomic urogenital tract abnormalities was conducted from 2000 to 2004 among 502 children one month to 7 years of age in 28 primary care practices in northern Italy. Escherichia coli was the pathogen in 436/462 (94.4%) of urine cultures. Antimicrobial resistance was 25/407 (6%) to amoxicillin-clavulanate and 3/343 (< 1%) to ceftriaxone. Ultrasonography and DMSA scintigraphy were planned no later than 10 days after initiation of antibiotic treatment.
The primary outcome measurement was renal scarring at 12 months, which was similar for both oral treatment only (27/197 [13.7%]) vs initial parenteral treatment (36/203 [17.7%]), risk difference -4% (95% CI, 11.1% to 3.1%). Renal scarring was also similar among the 278 children with pyelonephritis that was confirmed by DMSA scintigraphy (26/96 [27.8%] vs 33/100 [33%]). There were no significant differences between the 2 groups for secondary outcomes of: time to defervescence (36.9 hours [SD 19.7 hours] vs 34.3 hours [SD 20 hours], mean difference 2.6 hours [ 0.9 to 6.0 hours]); white cell count (9.8x109/L [SD 3.5 x109/L] vs 9.5x109/L [SD 3.1x109/L], mean difference 0.3x109/L [ 0.3 to 0.9x109/L]); and sterile urine after 3 days (185/186 vs 203/204, risk difference 0.05% [95% CI, 1.5% to 1.4%]). One patient in each group had a positive urine culture after 3 days; each had E. coli cultured initially and Pseudomonas aeruginosa cultured on the second urine sample. The duration of hospitalization was similar in both groups (5.17 days vs 5.05 days); by study design all children were hospitalized for a minimum of 3 days.
Acute pyelonephritis in young children is a serious concern because of the risk for sepsis, and especially the risk of sequelae of renal scarring, which is thought to be partially preventable by prompt, adequate treatment of acute infections. The recommendations for initial treatment of uncomplicated first urinary tract infections include broad guidelines that permit both parenteral and oral regimens, according to the judgment of the physician. Pediatricians have traditionally considered pyelonephritis, or upper tract infection, as more serious and requiring initial parenteral therapy, while oral therapy is considered sufficient for cystitis, or lower tract disease. However, there are no reliable, routinely available methods to clinically distinguish between upper and lower tract infections, and pediatricians frequently presume the presence of upper tract disease and initiate parenteral therapy.
Numerous studies of various parenteral antibiotic regimens have shown effectiveness for treatment of urinary tract infections in children. Only one previous study, among children < 2 years of age, compared exclusive oral treatment with initial parenteral antibiotics, and showed no difference in renal scarring (9.8% of children treated orally vs 7.2% of children treated intravenously; mean extent of scarring of approximately 8% in both groups) between the 2 groups at 6 months. This new study shows that the first urinary tract infection in children < 6 years of age without urogenital tract abnormalities may be effectively treated with an exclusive regimen of oral amoxicillin-clavulanate for 10 days. This has the obvious advantages of ease of administration and also, as outpatient therapy, the potential to reduce healthcare costs without adversely affecting outcome. Adherence to an oral antibiotic regimen at home is critical.