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Meta-Analysis
. 2014 Jul 28;2014(7):CD003772.
doi: 10.1002/14651858.CD003772.pub4.

Antibiotics for acute pyelonephritis in children

Yvonne Strohmeier  1 , Elisabeth M Hodson, Narelle S Willis, Angela C Webster, Jonathan C Craig
Affiliations
Meta-Analysis

Antibiotics for acute pyelonephritis in children

Yvonne Strohmeier et al. Cochrane Database Syst Rev. .

Abstract

Background: Urinary tract infection (UTI) is one of the most common bacterial infections in infants. The most severe form of UTI is acute pyelonephritis, which results in significant acute morbidity and may cause permanent kidney damage. There remains uncertainty regarding the optimum antibiotic regimen, route of administration and duration of treatment. This is an update of a review that was first published in 2003 and updated in 2005 and 2007.

Objectives: To evaluate the benefits and harms of antibiotics used to treat children with acute pyelonephritis. The aspects of therapy considered were 1) different antibiotics, 2) different dosing regimens of the same antibiotic, 3) different duration of treatment, and 4) different routes of administration.

Search methods: We searched the Cochrane Renal Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, reference lists of articles and conference proceedings without language restriction to 10 April 2014.

Selection criteria: Randomised and quasi-randomised controlled trials comparing different antibiotic agents, routes, frequencies or durations of therapy in children aged 0 to 18 years with proven UTI and acute pyelonephritis were selected.

Data collection and analysis: Four authors independently assessed study quality and extracted data. Statistical analyses were performed using the random-effects model and the results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous data with 95% confidence intervals (CI).

Main results: This updated review included 27 studies (4452 children). This update included evidence from three new studies, and following re-evaluation, a previously excluded study was included because it now met our inclusion criteria.Risk of bias was assessed as low for sequence generation (12 studies), allocation concealment (six studies), blinding of outcome assessors (17 studies), incomplete outcome reporting (19 studies) and selective outcome reporting (13 studies). No study was blinded for participants or investigators. The 27 included studies evaluated 12 different comparisons. No significant differences were found in duration of fever (2 studies, 808 children: MD 2.05 hours, 95% CI -0.84 to 4.94), persistent UTI at 72 hours after commencing therapy (2 studies, 542 children: RR 1.10, 95% CI 0.07 to 17.41) or persistent kidney damage at six to 12 months (4 studies, 943 children: RR 0.82, 95% CI 0.59 to 1.12) between oral antibiotic therapy (10 to 14 days) and intravenous (IV) therapy (3 days) followed by oral therapy (10 days). Similarly, no significant differences in persistent bacteriuria at the end of treatment (4 studies, 305 children: RR 0.78, 95% CI 0.24 to 2.55) or persistent kidney damage (4 studies, 726 children: RR 1.01, 95% CI 0.80 to 1.29) were found between IV therapy (three to four days) followed by oral therapy and IV therapy (seven to 14 days). No significant differences in efficacy were found between daily and thrice daily administration of aminoglycosides (1 study, 179 children, persistent clinical symptoms at three days: RR 1.98, 95% CI 0.37 to 10.53). Adverse events were mild and uncommon and rarely resulted in discontinuation of treatment.

Authors' conclusions: This updated review increases the body of evidence that oral antibiotics alone are as effective as a short course (three to four days) of IV antibiotics followed by oral therapy for a total treatment duration of 10 to 14 days for the treatment of acute pyelonephritis in children. When IV antibiotics are given, a short course (two to four days) of IV therapy followed by oral therapy is as effective as a longer course (seven to 10 days) of IV therapy. If IV therapy with aminoglycosides is chosen, single daily dosing is safe and effective. Insufficient data are available to extrapolate these findings to children aged less than one month of age or to children with dilating vesicoureteric reflux (grades III-V). Further studies are required to determine the optimal total duration of antibiotic therapy required for acute pyelonephritis.

PubMed Disclaimer

Conflict of interest statement

Yvonne Strohmeier: nothing to declare Elisabeth Hodson: nothing to declare Narelle Willis: nothing to declare Angela Webster: nothing to declare Jonathan Craig: nothing to declare

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Oral versus IV followed by oral (11 days) therapy, Outcome 1 Time to fever resolution.
1.2
1.2. Analysis
Comparison 1 Oral versus IV followed by oral (11 days) therapy, Outcome 2 Fever on Day 3.
1.3
1.3. Analysis
Comparison 1 Oral versus IV followed by oral (11 days) therapy, Outcome 3 Number with persistent UTI at 72 hours.
1.4
1.4. Analysis
Comparison 1 Oral versus IV followed by oral (11 days) therapy, Outcome 4 Inflammatory markers at 72 hours.
1.5
1.5. Analysis
Comparison 1 Oral versus IV followed by oral (11 days) therapy, Outcome 5 Recurrent UTI within 6 months.
1.6
1.6. Analysis
Comparison 1 Oral versus IV followed by oral (11 days) therapy, Outcome 6 Persistent kidney damage at 6‐12 months.
1.7
1.7. Analysis
Comparison 1 Oral versus IV followed by oral (11 days) therapy, Outcome 7 Proportion of kidney parenchyma with damage at 6 months.
1.8
1.8. Analysis
Comparison 1 Oral versus IV followed by oral (11 days) therapy, Outcome 8 Kidney damage at 6 months (post hoc subgroup analysis).
2.1
2.1. Analysis
Comparison 2 Short duration (3‐4 days) versus long duration (7‐14 days) IV therapy, Outcome 1 Persistent bacteriuria after treatment.
2.2
2.2. Analysis
Comparison 2 Short duration (3‐4 days) versus long duration (7‐14 days) IV therapy, Outcome 2 Recurrent UTI within 6 months.
2.3
2.3. Analysis
Comparison 2 Short duration (3‐4 days) versus long duration (7‐14 days) IV therapy, Outcome 3 Persistent kidney damage at 3‐6 months.
2.4
2.4. Analysis
Comparison 2 Short duration (3‐4 days) versus long duration (7‐14 days) IV therapy, Outcome 4 Persistent kidney damage at 3‐6 months (post hoc subgroup analysis).
2.5
2.5. Analysis
Comparison 2 Short duration (3‐4 days) versus long duration (7‐14 days) IV therapy, Outcome 5 Adverse effects.
3.1
3.1. Analysis
Comparison 3 Single dose parenteral therapy and oral therapy versus oral therapy alone, Outcome 1 Persistent bacteriuria at 48 hours.
3.2
3.2. Analysis
Comparison 3 Single dose parenteral therapy and oral therapy versus oral therapy alone, Outcome 2 Treatment failure after 48 hours of therapy.
3.3
3.3. Analysis
Comparison 3 Single dose parenteral therapy and oral therapy versus oral therapy alone, Outcome 3 Recurrent UTI within 1 month.
3.4
3.4. Analysis
Comparison 3 Single dose parenteral therapy and oral therapy versus oral therapy alone, Outcome 4 Adverse events.
4.1
4.1. Analysis
Comparison 4 Different dosing regimens of aminoglycosides (daily versus 8 hourly), Outcome 1 Persistent bacteriuria after 1‐3 days of treatment.
4.2
4.2. Analysis
Comparison 4 Different dosing regimens of aminoglycosides (daily versus 8 hourly), Outcome 2 Persistent symptoms at end of 3 days of IV therapy.
4.3
4.3. Analysis
Comparison 4 Different dosing regimens of aminoglycosides (daily versus 8 hourly), Outcome 3 Persistent bacteriuria at 1 week after treatment.
4.4
4.4. Analysis
Comparison 4 Different dosing regimens of aminoglycosides (daily versus 8 hourly), Outcome 4 Reinfection at 1 month after completing treatment.
4.5
4.5. Analysis
Comparison 4 Different dosing regimens of aminoglycosides (daily versus 8 hourly), Outcome 5 Hearing impairment following treatment.
4.6
4.6. Analysis
Comparison 4 Different dosing regimens of aminoglycosides (daily versus 8 hourly), Outcome 6 Increase in serum creatinine during treatment.
4.7
4.7. Analysis
Comparison 4 Different dosing regimens of aminoglycosides (daily versus 8 hourly), Outcome 7 Time to resolution of fever.
4.8
4.8. Analysis
Comparison 4 Different dosing regimens of aminoglycosides (daily versus 8 hourly), Outcome 8 Kidney parenchymal damage at 3 months.
5.1
5.1. Analysis
Comparison 5 Third generation cephalosporin versus other antibiotic, Outcome 1 Persistent bacteriuria.
5.2
5.2. Analysis
Comparison 5 Third generation cephalosporin versus other antibiotic, Outcome 2 Recurrent UTI after end of therapy.
5.3
5.3. Analysis
Comparison 5 Third generation cephalosporin versus other antibiotic, Outcome 3 Persistent symptoms after end of treatment.
5.4
5.4. Analysis
Comparison 5 Third generation cephalosporin versus other antibiotic, Outcome 4 Number with fever for more than 48 hours.
5.5
5.5. Analysis
Comparison 5 Third generation cephalosporin versus other antibiotic, Outcome 5 Recurrent bacteriuria at 4‐6 weeks.
5.6
5.6. Analysis
Comparison 5 Third generation cephalosporin versus other antibiotic, Outcome 6 Recurrent symptomatic UTI at 4‐6 weeks.
5.7
5.7. Analysis
Comparison 5 Third generation cephalosporin versus other antibiotic, Outcome 7 Gastrointestinal adverse events.
5.8
5.8. Analysis
Comparison 5 Third generation cephalosporin versus other antibiotic, Outcome 8 Number discontinuing treatment for adverse effect.
6.1
6.1. Analysis
Comparison 6 Cefepime versus ceftazidime, Outcome 1 Persistence or recurrence of initial pathogen.
6.2
6.2. Analysis
Comparison 6 Cefepime versus ceftazidime, Outcome 2 Infection with new pathogen at 4‐6 weeks.
6.3
6.3. Analysis
Comparison 6 Cefepime versus ceftazidime, Outcome 3 Unsatisfactory clinical response.
6.4
6.4. Analysis
Comparison 6 Cefepime versus ceftazidime, Outcome 4 Adverse effects.
7.1
7.1. Analysis
Comparison 7 Ceftriaxone versus cefotaxime, Outcome 1 Persistent bacteriuria at 48 hours.
7.2
7.2. Analysis
Comparison 7 Ceftriaxone versus cefotaxime, Outcome 2 Bacteriuria 10 days after end of treatment.
7.3
7.3. Analysis
Comparison 7 Ceftriaxone versus cefotaxime, Outcome 3 UTI at 1 month after therapy.
7.4
7.4. Analysis
Comparison 7 Ceftriaxone versus cefotaxime, Outcome 4 Adverse events.
8.1
8.1. Analysis
Comparison 8 Isepamicin versus amikacin, Outcome 1 Persistent bacteriuria.
9.1
9.1. Analysis
Comparison 9 10 days versus 42 days of oral sulfafurazole, Outcome 1 Recurrent UTI within 1 month after ceasing therapy.
9.2
9.2. Analysis
Comparison 9 10 days versus 42 days of oral sulfafurazole, Outcome 2 Recurrent UTI at 1‐12 months after completing therapy.
10.1
10.1. Analysis
Comparison 10 Single dose of parenteral antibiotic versus 7‐10 days oral therapy, Outcome 1 Persistent bacteriuria 1‐2 days after treatment.
10.2
10.2. Analysis
Comparison 10 Single dose of parenteral antibiotic versus 7‐10 days oral therapy, Outcome 2 UTI relapse or reinfection within 6 weeks.
11.1
11.1. Analysis
Comparison 11 3 weeks versus 2 weeks, Outcome 1 Persistence/recurrence of bacteriuria.
11.2
11.2. Analysis
Comparison 11 3 weeks versus 2 weeks, Outcome 2 Recurrence of clinical UTI.
12.1
12.1. Analysis
Comparison 12 Suppositories versus oral ampicillin, Outcome 1 Persistence of clinical symptoms.
12.2
12.2. Analysis
Comparison 12 Suppositories versus oral ampicillin, Outcome 2 Persistence of bacteriuria.
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

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Hoberman 1999 {published and unpublished data}
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Levtchenko 2001 {published data only}
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Marild 2009 {published data only}
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Noorbakhsh 2004 {published data only}
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References to studies excluded from this review

Adam 1982 {published data only}
    1. Adam D, Hager C, Dorn G, Bamberg P. A comparison of co‐trimazine once daily and co‐trimoxazole twice daily in treatment of urinary tract infections in children. Journal of Antimicrobial Chemotherapy 1982;10(5):453‐8. [MEDLINE: ] - PubMed
Avner 1983 {published data only}
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Belet 2004 {published data only}
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Bose 1974 {published data only}
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Clemente 1994 {published data only}
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Cox 1985 {published data only}
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Dagan 1992 {published data only}
    1. Dagan R, Einhorn M, Lang R, Pomeranz A, Wolach B, Miron D, et al. Once daily cefixime compared with twice daily trimethoprim/sulfamethoxazole for the treatment of urinary tract infection in infants and children. Pediatric Infectious Disease Journal 1992;11(3):198‐203. [MEDLINE: ] - PubMed
Ellerstein 1977 {published data only}
    1. Ellerstein NS, Sullivan TD, Baliah T, Neter E. Trimethoprim/sulfamethoxazole and ampicillin in the treatment of acute urinary tract infections in children: a double‐blind study. Pediatrics 1977;60(2):245‐7. [MEDLINE: ] - PubMed
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Fine 1985 {published data only}
    1. Fine JS, Jacobson MS. Single‐dose versus conventional therapy of urinary tract infections in female adolescents. Pediatrics 1985;75(5):916‐20. [MEDLINE: ] - PubMed
Francois 1995 {published data only}
    1. Francois P, Croizé J, Bost C, Wollschlager K. Comparative study of cefixime versus amoxycillin‐clavulanate for oral treatment of urinary tract infections in children [Étude comparant le céfixime à l'association amoxicilline‐acide clavulanique dans le traitement par voie orale des infections urinaires de l'enfant]. Archives de Pediatrie 1995;2(2):136‐42. [MEDLINE: ] - PubMed
Garin 2006 {published data only}
    1. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics 2006;117(3):626‐32. [MEDLINE: ] - PubMed
Ginsburg 1982 {published data only}
    1. Ginsburg CM, McCracken GH, Petruska M. Once‐daily cefadroxil versus twice‐daily cefaclor for treatment of acute urinary tract infections in children. Journal of Antimicrobial Chemotherapy 1982;10(Suppl B):53‐6. [MEDLINE: ] - PubMed
Godard 1980 {published data only}
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Gok 2001 {published data only}
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References to ongoing studies

NCT00724256 {published data only}
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Additional references

AAP 2011
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References to other published versions of this review

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