Randomised trial of oral versus sequential intravenous/oral cephalosporins in children with pyelonephritis (original) (raw)

Abstract

The hypothesis was tested that oral antibiotic treatment in children with acute pyelonephritis and scintigraphy-documented lesions is equally as efficacious as sequential intravenous/oral therapy with respect to the incidence of renal scarring. A randomised multi-centre trial was conducted in 365 children aged 6 months to 16 years with bacterial growth in cultures from urine collected by catheter. The children were assigned to receive either oral ceftibuten (9 mg/kg once daily) for 14 days or intravenous ceftriaxone (50 mg/kg once daily) for 3 days followed by oral ceftibuten for 11 days. Only patients with lesions detected on acute-phase dimercaptosuccinic acid (DMSA) scintigraphy underwent follow-up scintigraphy. Efficacy was evaluated by the rate of renal scarring after 6 months on follow-up scintigraphy. Of 219 children with lesions on acute-phase scintigraphy, 152 completed the study; 80 (72 females, median age 2.2 years) were given ceftibuten and 72 (62 females, median age 1.6 years) were given ceftriaxone/ceftibuten. Patients in the intravenous/oral group had significantly higher C-reactive protein (CRP) concentrations at baseline and larger lesion(s) on acute-phase scintigraphy. Follow-up scintigraphy showed renal scarring in 21/80 children treated with ceftibuten and 33/72 with ceftriaxone/ceftibuten (p = 0.01). However, after adjustment for the confounding variables (CRP and size of acute-phase lesion), no significant difference was observed for renal scarring between the two groups (p = 0.2). Renal scarring correlated with the extent of the acute-phase lesion (r = 0.60, p < 0.0001) and the grade of vesico-ureteric reflux (r = 0.31, p = 0.03), and was more frequent in refluxing renal units (p = 0.04). The majority of patients, i.e. 44 in the oral group and 47 in the intravenous/oral group, were managed as out-patients. Side effects were not observed. From this study, we can conclude that once-daily oral ceftibuten for 14 days yielded comparable results to sequential ceftriaxone/ceftibuten treatment in children aged 6 months to 16 years with DMSA-documented acute pyelonephritis and it allowed out-patient management in the majority of these children.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Abbreviations

CRP:

C-reactive protein

DMSA:

Dimercaptosuccinic acid

VUR:

Vesico-ureteric reflux

References

  1. American Academy of Pediatrics, Committee on Quality Improvement, Subcommittee on Urinary Tract Infection (1999) Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics 103:843–852
    Google Scholar
  2. Bachur R, Caputo GL (1995) Bacteremia and meningitis among infants with urinary tract infections. Pediatr Emerg Care 11:280–284
    Article PubMed CAS Google Scholar
  3. Banfi A, Gabriele G, Hill-Juarez JM, Kaufman A, Moens E, group amotcutiis (1993) Multinational comparative trial of ceftibuten and trimethoprim-sulfamethoxazole in the treatment of children with complicated or recurrent urinary tract infections. Pediatr Infect Dis J 12:S84–S91
    Google Scholar
  4. Barr WH, Affrime M, Lin CC, Batra V (1995) Pharmacokinetics of ceftibuten in children. Pediatr Infect Dis J 14:S93–S101
    PubMed CAS Google Scholar
  5. Benador D, Neuhaus TJ, Papazyan JP, Willi UV, Engel-Bicik I, Nadal D, Slosman D, Mermillod B, Girardin E (2001) Randomised controlled trial of three day versus 10 day intravenous antibiotics in acute pyelonephritis: effect on renal scarring. Arch Dis Child 84:241–246
    Article PubMed CAS Google Scholar
  6. Bloomfield P, Hodson EM, Craig JC (2003) Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev:CD003772
  7. Crain EF, Gershel JC (1990) Urinary tract infections in febrile infants younger than 8 weeks of age. Pediatrics 86:363–367
    PubMed CAS Google Scholar
  8. de La Vaissière B, Castello B, Quinet B, Cohen R, Grimprel E (2006) Management of acute pyelonephritis in patients older than 3 months: survey conducted in 39 paediatric emergency departments of the Ile de France Region in 2004. Arch Pediatr 13:245–250
    Article Google Scholar
  9. Ditchfield MR, Grimwood K, Cook DJ, Powell HR, Sloane R, Gulati S, De Campo JF (2004) Persistent renal cortical scintigram defects in children 2 years after urinary tract infection. Pediatr Radiol 34:465–471
    Article PubMed Google Scholar
  10. Goldraich NP, Goldraich IH (1995) Update on dimercaptosuccinic acid renal scanning in children with urinary tract infection. Pediatr Nephrol 9:221–226
    Article PubMed CAS Google Scholar
  11. Goldraich NP, Ramos OL, Goldraich IH (1989) Urography versus DMSA scan in children with vesicoureteric reflux. Pediatr Nephrol 3:1–5
    Article PubMed CAS Google Scholar
  12. González E, Papazyan JP, Girardin E (2005) Impact of vesicoureteral reflux on the size of renal lesions after an episode of acute pyelonephritis. J Urol 173:571–574; Discussion 574–575
    Article PubMed Google Scholar
  13. Group SPN (2001) Treatment of urinary tract infections in children. Paediatrica 12:16–21
    Google Scholar
  14. Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, Majd M, Kearney DH, Reynolds EA, Ruley J, Janosky JE (1999) Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics 104:79–86
    Article PubMed CAS Google Scholar
  15. Jakobsson B, Berg U, Svensson L (1994) Renal scarring after acute pyelonephritis. Arch Dis Child 70:111–115
    Article PubMed CAS Google Scholar
  16. Jakobsson B, Svensson L (1997) Transient pyelonephritic changes on 99mTechnetium-dimercaptosuccinic acid scan for at least five months after infection. Acta Paediatr 86:803–807
    Article PubMed CAS Google Scholar
  17. Jones RN (1995) Ceftibuten: a review of antimicrobial activity, spectrum and other microbiologic features. Pediatr Infect Dis J 14:S77–83
    Article PubMed CAS Google Scholar
  18. Kavanagh EC, Ryan S, Awan A, McCourbrey S, O’Connor R, Donoghue V (2005) Can MRI replace DMSA in the detection of renal parenchymal defects in children with urinary tract infections? Pediatr Radiol 35:275–281
    Article PubMed Google Scholar
  19. Klepser ME, Marangos MN, Patel KB, Nicolau DP, Quintiliani R, Nightingale CH (1995) Clinical pharmacokinetics of newer cephalosporins. Clin Pharmacokinet 28:361–384
    Article PubMed CAS Google Scholar
  20. Lahdes-Vasama T, Niskanen K, Rönnholm K (2006) Outcome of kidneys in patients treated for vesicoureteral reflux (VUR) during childhood. Nephrol Dial Transplant 21:2491–2497
    Article PubMed Google Scholar
  21. Montini G, Toffolo A, Zucchetta P, Dall’Amico R, Gobber D, Calderan A, Maschio F, Pavanello L, Molinari PP, Scorrano D, Zanchetta S, Cassar W, Brisotto P, Corsini A, Sartori S, Da Dalt L, Murer L, Zacchello G (2007) Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial. BMJ 335:386
    Article PubMed CAS Google Scholar
  22. Moorthy I, Easty M, McHugh K, Ridout D, Biassoni L, Gordon I (2005) The presence of vesicoureteric reflux does not identify a population at risk for renal scarring following a first urinary tract infection. Arch Dis Child 90:733–736
    Article PubMed CAS Google Scholar
  23. Neu HC (1995) Ceftibuten: minimal inhibitory concentrations, postantibiotic effect and beta-lactamase stability—a rationale for dosing programs. Pediatr Infect Dis J 14:S88–S92
    Article PubMed CAS Google Scholar
  24. Orellana P, Baquedano P, Rangarajan V, Zhao JH, Eng ND, Fettich J, Chaiwatanarat T, Sonmezoglu K, Kumar D, Park YH, Samuel AM, Sixt R, Bhatnagar V, Padhy AK (2004) Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux. Results of a coordinated research project. Pediatr Nephrol 19:1122–1126
    Article PubMed Google Scholar
  25. Pitetti RD, Choi S (2002) Utility of blood cultures in febrile children with UTI. Am J Emerg Med 20:271–274
    Article PubMed Google Scholar
  26. Polito C, Rambaldi PF, Signoriello G, Mansi L, La Manna A (2006) Permanent renal parenchymal defects after febrile UTI are closely associated with vesicoureteric reflux. Pediatr Nephrol 21:521–526
    Article PubMed Google Scholar
  27. Prère MF, Licznar P, Decramer S, Fayet O (2004) E. coli from urinary tract infections and acute pyelonephritis of children: 1% of strains are resistant to a subset of third generation cephalosporins. Pathol Biol (Paris) 52:497–500
    Google Scholar
  28. Reidenberg BE (1995) Worldwide safety experience with ceftibuten pediatric suspension. Pediatr Infect Dis J 14:S130–S133
    Article PubMed CAS Google Scholar
  29. Rushton HG, Majd M (1992) Dimercaptosuccinic acid renal scintigraphy for the evaluation of pyelonephritis and scarring: a review of experimental and clinical studies. J Urol 148:1726–1732
    PubMed CAS Google Scholar
  30. Stokland E, Hellström M, Jacobsson B, Jodal U, Sixt R (1996) Renal damage one year after first urinary tract infection: role of dimercaptosuccinic acid scintigraphy. J Pediatr 129:815–820
    Article PubMed CAS Google Scholar
  31. Vilaichone A, Watana D, Chaiwatanarat T (2001) Oral ceftibuten switch therapy for acute pyelonephritis in children. J Med Assoc Thai 84(Suppl 1):S61–S67
    PubMed Google Scholar
  32. Wennerström M, Hansson S, Hedner T, Himmelmann A, Jodal U (2000) Ambulatory blood pressure 16–26 years after the first urinary tract infection in childhood. J Hypertens 18:485–491
    Article PubMed Google Scholar
  33. Wennerström M, Hansson S, Jodal U, Sixt R, Stokland E (2000) Renal function 16 to 26 years after the first urinary tract infection in childhood. Arch Pediatr Adolesc Med 154:339–345
    PubMed Google Scholar
  34. Wiseman LR, Balfour JA (1994) Ceftibuten. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs 47:784–808
    Article PubMed CAS Google Scholar
  35. Zaki M, Badawi M, Al Mutari G, Ramadan D, Adul Rahman M (2005) Acute pyelonephritis and renal scarring in Kuwaiti children: a follow-up study using 99mTc DMSA renal scintigraphy. Pediatr Nephrol 20:1116–1119
    Article PubMed Google Scholar

Download references

Author information

Authors and Affiliations

  1. Department of Nephrology, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland
    Thomas J. Neuhaus
  2. Department of General Paediatrics, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland
    Thomas J. Neuhaus & Sergio Stocker
  3. Department of Infectious Diseases, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland
    Christoph Berger, Katja Buechner & David Nadal
  4. Department of Radiology, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland
    Ulrich Willi
  5. Child Development Center, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland
    Luciano Molinari
  6. Department of Nephrology, University Children’s Hospital Geneva, 1211, Geneva 14, Switzerland
    Paloma Parvex, Alain Gervaix & Eric Girardin
  7. Department of Paediatrics, Cantonal Hospital Winterthur, 8400, Winterthur, Switzerland
    Gian Bischoff & Urs Hunziker
  8. Department of Paediatrics, City Hospital Zurich-Triemli, 8063, Zurich, Switzerland
    Philippe Goetschel
  9. Department of Nuclear Medicine, University Hospital Zurich, 8091, Zurich, Switzerland
    Daniela Husarik
  10. Department of Nephrology, University Children’s Hospital Basle, 4005, Basle, Switzerland
    Christoph Rudin

Authors

  1. Thomas J. Neuhaus
    You can also search for this author inPubMed Google Scholar
  2. Christoph Berger
    You can also search for this author inPubMed Google Scholar
  3. Katja Buechner
    You can also search for this author inPubMed Google Scholar
  4. Paloma Parvex
    You can also search for this author inPubMed Google Scholar
  5. Gian Bischoff
    You can also search for this author inPubMed Google Scholar
  6. Philippe Goetschel
    You can also search for this author inPubMed Google Scholar
  7. Daniela Husarik
    You can also search for this author inPubMed Google Scholar
  8. Ulrich Willi
    You can also search for this author inPubMed Google Scholar
  9. Luciano Molinari
    You can also search for this author inPubMed Google Scholar
  10. Christoph Rudin
    You can also search for this author inPubMed Google Scholar
  11. Alain Gervaix
    You can also search for this author inPubMed Google Scholar
  12. Urs Hunziker
    You can also search for this author inPubMed Google Scholar
  13. Sergio Stocker
    You can also search for this author inPubMed Google Scholar
  14. Eric Girardin
    You can also search for this author inPubMed Google Scholar
  15. David Nadal
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toDavid Nadal.

Additional information

TJN, CB and KB contributed equally to this work. EG and DN share senior authorship.

Trial number: Register of the Swiss national agency for therapeutic products (Swissmedic).Reference number: IKS 2001S03204

Rights and permissions

About this article

Cite this article

Neuhaus, T.J., Berger, C., Buechner, K. et al. Randomised trial of oral versus sequential intravenous/oral cephalosporins in children with pyelonephritis.Eur J Pediatr 167, 1037–1047 (2008). https://doi.org/10.1007/s00431-007-0638-1

Download citation

Keywords