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Longer treatment with intravenous antibiotics does not decrease rate of renal scarring in children with pyelonephritis
CURRENT BEST EVIDENCE
Clinical Research Abstracts for Pediatricians EDITOR’S NOTE: Journals reviewed for this issue: Archives of Disease in Childhood, Archives of Pediatrics and Adolescent Medicine, British Medical Journal, Journal of the American Medical Association, Journal of Pediatrics, The Lancet, New England Journal of Medicine, Pediatric Infectious Diseases Journal, and Pediatrics. Gurpreet K. Rana, BSc, MLIS, Taubman Medical Library, University of Michigan, contributed to the review and selection of this month’s abstracts. —John G. Frohna, MD, MPH
Longer treatment with intravenous antibiotics does not decrease rate of renal scarring in children with pyelonephritis 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 Clinical Research Abstracts for Pediatricians
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 shortterm 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 ex439
cluded 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. Ellen R. Wald, MD University of Wisconsin American Family Children’s Hospital Madison, Wisconsin
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;104:127-9.
Delayed introduction of solids does not decrease the incidence of asthma or allergic rhinitis Zutavern A, Brockow I, Schaaf B, von Berg A, Diez U, Borte M, et al., LISA Study Group. Timing of solid food introduction in relation to eczema, asthma, allergic rhinitis, and food and inhalant sensitization at the age of 6 years: results from the prospective birth cohort study LISA. Pediatrics 2008; 121:e44-52. Question Does a delayed introduction of solids (past 4 or 6 months) protect against the development of eczema, asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years? Design Prospective cohort study. Data from were analyzed at
6 years of age. Multivariate logistic regression analyses were performed for all children and for children without skin or allergic symptoms within the first 6 months of life to take into account reverse causality. Setting Germany. Participants A total of 2073 children in the ongoing LISA birth cohort study. Intervention Questionnaires were completed by the parents
at birth and when the children were 0.5, 1, 1.5, 2, 4, and 6 years of age. At age 2 and 6 years, children also underwent blood collection and physical examination. Outcomes Physician diagnoses of eczema, asthma, and allergic rhinitis (collected through parent report and medical records). Main Results A delayed introduction of solids (past 4 or 6 months) was not associated with decreased odds for asthma, allergic rhinitis, or sensitization against food or inhalant al-
440
lergens at 6 years of age. On the contrary, food sensitization was more frequent in children who were introduced to solids later. The relationship between the timing of solid food introduction and eczema was not clear. There was no protective effect of a late introduction of solids or a less diverse diet within the first 4 months of life. However, in children without early skin or allergic symptoms, eczema was significantly more frequent in children who received a more diverse diet within the first 4 months. Conclusions There is no evidence that delayed introduction of solids beyond 4 or 6 months prevents asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years. For eczema, the results were conflicting, and a protective effect of a delayed introduction of solids cannot be excluded. A true protective effect of a delayed introduction of solids on food sensitization seems unlikely. Commentary “When should I start feeding my baby solids?” This is a question pediatricians and family physicians confront regularly— especially given the rising incidence of allergy in children and the suspicion that infant dietary practices play a role. However, most evidence behind the recommendations for the timing of solid food introduction for infants has been conflicting and of limited quality. Against this backdrop, the analysis of the LISA birth cohort contributes high-quality evidence of the relationship between infant feeding and allergic disease in the largest birth cohort studied to date. In this study, the authors examined whether delayed introduction of solid foods (⬎4 or ⬎6 months) prevents the development of allergic disease. Conducting research on infant feeding poses a number of challenges. First, there is the potential for parent recall bias and the use of imprecise definitions to classify disease. The authors overcame these issues by obtaining prospective feeding histories, collecting disease reports from parents and physicians, and conducting the analysis at 6 years of age—when asthma and allergic rhinitis are easier to diagnose. Second, there is the challenge of reverse causality that occurs when parents of infants with early allergy symptoms delay introduction of solids. This results in a false association between late feeding and allergic symptoms. To address this bias, the authors stratified their analyses by report of early allergy symptoms but still found no relationship between delayed introduction of solids and development of asthma, allergic rhinitis, and food or inhalant sensitization. However, the results for eczema were conflicting, a finding that will likely influence physicians’ recommendations for infants with eczema or a positive family history. Overall, this is a well-conducted study that provides useful evidence on infant feeding practices for pediatric practitioners and parents.
Beth Tarini, MD, MS University of Michigan Ann Arbor, Michigan
The Journal of Pediatrics • September 2008
Clinical Research Abstracts for Pediatricians EDITOR’S NOTE: Journals reviewed for this issue: Archives of Disease in Childhood, Archives of Pediatrics and Adolescent Medicine, British Medical Journal, Journal of the American Medical Association, Journal of Pediatrics, The Lancet, New England Journal of Medicine, Pediatric Infectious Diseases Journal, and Pediatrics. Gurpreet K. Rana, BSc, MLIS, Taubman Medical Library, University of Michigan, contributed to the review and selection of this month’s abstracts. —John G. Frohna, MD, MPH
Longer treatment with intravenous antibiotics does not decrease rate of renal scarring in children with pyelonephritis 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 Clinical Research Abstracts for Pediatricians
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 shortterm 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 ex439
cluded 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. Ellen R. Wald, MD University of Wisconsin American Family Children’s Hospital Madison, Wisconsin
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;104:127-9.
Delayed introduction of solids does not decrease the incidence of asthma or allergic rhinitis Zutavern A, Brockow I, Schaaf B, von Berg A, Diez U, Borte M, et al., LISA Study Group. Timing of solid food introduction in relation to eczema, asthma, allergic rhinitis, and food and inhalant sensitization at the age of 6 years: results from the prospective birth cohort study LISA. Pediatrics 2008; 121:e44-52. Question Does a delayed introduction of solids (past 4 or 6 months) protect against the development of eczema, asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years? Design Prospective cohort study. Data from were analyzed at
6 years of age. Multivariate logistic regression analyses were performed for all children and for children without skin or allergic symptoms within the first 6 months of life to take into account reverse causality. Setting Germany. Participants A total of 2073 children in the ongoing LISA birth cohort study. Intervention Questionnaires were completed by the parents
at birth and when the children were 0.5, 1, 1.5, 2, 4, and 6 years of age. At age 2 and 6 years, children also underwent blood collection and physical examination. Outcomes Physician diagnoses of eczema, asthma, and allergic rhinitis (collected through parent report and medical records). Main Results A delayed introduction of solids (past 4 or 6 months) was not associated with decreased odds for asthma, allergic rhinitis, or sensitization against food or inhalant al-
440
lergens at 6 years of age. On the contrary, food sensitization was more frequent in children who were introduced to solids later. The relationship between the timing of solid food introduction and eczema was not clear. There was no protective effect of a late introduction of solids or a less diverse diet within the first 4 months of life. However, in children without early skin or allergic symptoms, eczema was significantly more frequent in children who received a more diverse diet within the first 4 months. Conclusions There is no evidence that delayed introduction of solids beyond 4 or 6 months prevents asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years. For eczema, the results were conflicting, and a protective effect of a delayed introduction of solids cannot be excluded. A true protective effect of a delayed introduction of solids on food sensitization seems unlikely. Commentary “When should I start feeding my baby solids?” This is a question pediatricians and family physicians confront regularly— especially given the rising incidence of allergy in children and the suspicion that infant dietary practices play a role. However, most evidence behind the recommendations for the timing of solid food introduction for infants has been conflicting and of limited quality. Against this backdrop, the analysis of the LISA birth cohort contributes high-quality evidence of the relationship between infant feeding and allergic disease in the largest birth cohort studied to date. In this study, the authors examined whether delayed introduction of solid foods (⬎4 or ⬎6 months) prevents the development of allergic disease. Conducting research on infant feeding poses a number of challenges. First, there is the potential for parent recall bias and the use of imprecise definitions to classify disease. The authors overcame these issues by obtaining prospective feeding histories, collecting disease reports from parents and physicians, and conducting the analysis at 6 years of age—when asthma and allergic rhinitis are easier to diagnose. Second, there is the challenge of reverse causality that occurs when parents of infants with early allergy symptoms delay introduction of solids. This results in a false association between late feeding and allergic symptoms. To address this bias, the authors stratified their analyses by report of early allergy symptoms but still found no relationship between delayed introduction of solids and development of asthma, allergic rhinitis, and food or inhalant sensitization. However, the results for eczema were conflicting, a finding that will likely influence physicians’ recommendations for infants with eczema or a positive family history. Overall, this is a well-conducted study that provides useful evidence on infant feeding practices for pediatric practitioners and parents.
Beth Tarini, MD, MS University of Michigan Ann Arbor, Michigan
The Journal of Pediatrics • September 2008