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• Antibiotic resistance in urinary tract isolates and risk of renal scarring.
  Michael Eisenhut
  Published on: 25 June 2003
• Clinically relevant data needed to inform prescribing decisions
  Andrew Riordan
  Published on: 2 June 2003

• Published on: 25 June 2003

  Antibiotic resistance in urinary tract isolates and risk of renal scarring.

  • Michael Eisenhut, Paediatric Registrar
  • Other Contributors:
    • Faye El Masri, Caroline A. Jones

  Dear Editor

  Lakhani and Gransden [1] stated in their article that in urinary tract infection the initial use of an antibiotic the urinary tract isolate is resistant to will through a delay in effective treatment lead to an increased risk of renal scarring. The authors concluded that nitrofurantoin should replace trimethoprim as the first line antibiotic for treatment of urinary tract infection (UTI) in childhood beca...

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  Dear Editor

  Lakhani and Gransden [1] stated in their article that in urinary tract infection the initial use of an antibiotic the urinary tract isolate is resistant to will through a delay in effective treatment lead to an increased risk of renal scarring. The authors concluded that nitrofurantoin should replace trimethoprim as the first line antibiotic for treatment of urinary tract infection (UTI) in childhood because of the high rate of trimethoprim resistance. We recently presented [2] data from a case control study investigating the influence of delay of treatment associated with trimethoprim resistant UTI on renal scarring. We compared 23 children with and 101 children without renal scarring after their first UTI. The prevalence of renal scarring in patients with trimethoprim resistant organism initially treated with trimethoprim was 3/18 (17%) and 20/106 (19%) in patients, treated with the appropriate antibiotic (p=1.0). In patients with trimethoprim resistant organism treated with trimethoprim as antibiotic of first choice the delay in effective treatment ( median and range) in patients with renal scarring was 4 days (1-5) and in patients without renal scarring 2 days (0-8) (p=0.46). Our conclusion is, that having a prompt response to microbiological sensitivity testing did not delay the effective treatment of a UTI significantly and did not increase the risk of renal scarring. This was supported by a recent review,[3] which concluded that in studies, in which therapy was not more delayed than a week, there was no effect of treatment delay on the risk of renal scarring. We therefore have not changed our policy using oral trimethoprim as antibiotic of first choice in treating UTI in patients beyond infancy, tolerating oral antibiotics and not affected by septicemia.

  References

  (1) Ladhani S, Gransden W. Increasing antibiotic resistance among urinary tract isolates. Arch Dis Child 2003;88:444-5.

  (2) Eisenhut M, El Masri F, Murphy P, Jones CA. Risk factors for renal scarring in children with urinary tract infection-a retrospective case control study. Arch Dis Child 2003; 88 (Suppl I): A72.

  (3) Jakobsson B, Jacobson SH, Hjaelmas K. Vesico-ureteric reflux and other risk factors for renal damage: identification of high-and low-risk children. Acta Paediatr Suppl 1999;431:31-9.

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  Conflict of Interest:
  None declared.

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• Published on: 2 June 2003

  Clinically relevant data needed to inform prescribing decisions

  • Andrew Riordan, Consultant Paediatrician

  Dear Editor

  Ladhani and Gransden are right to encourage other units to review local data on antibiotic resistance among urinary tract isolates. There is not adequate evidence to suggest one antibiotic is superior to others in presumptive therapy of urinary tract infection (UTI).[1] Local antibiotic susceptibility patterns should thus help make the antibiotic choice. However I have two major concerns about their con...

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  Dear Editor

  Ladhani and Gransden are right to encourage other units to review local data on antibiotic resistance among urinary tract isolates. There is not adequate evidence to suggest one antibiotic is superior to others in presumptive therapy of urinary tract infection (UTI).[1] Local antibiotic susceptibility patterns should thus help make the antibiotic choice. However I have two major concerns about their conclusions:

  1. They do not demonstrate the clinical significance of their data and
  2. Empiric use of nitrofurantoin is not justified by their data.

  1. Clinical relevance of resistant organisms. One study shows that the bacteriological cure rate in UTI is the same irrespective of whether the infecting bacteria were sensitive or resistant to the antibiotic given.[2] The clinical significance of antibiotic resistant urinary tract isolates thus needs to be shown.

  Like Ladhani and Gransden we were concerned that 17% of urinary tract isolates cultured in our hospital were trimethoprim resistant. We therefore reviewed the case notes of 21 children with trimethoprim resistant urinary tract isolates. Of these 21, eight were found not to have a urinary tract infection, despite having a bacterial culture of 105 colony-forming units of a single species per ml urine. Most of these were samples collected in urine bags. 85% of positive cultures of urine specimens obtained from a bag are false positive results.[1] We have now abandoned the use of urine bags. Of the 13 thought to have UTI, seven were on trimethoprim prophylaxis and had breakthrough infections. Only six children had clinically significant trimethoprim resistant urinary tract isolates and were not on trimethoprim prophylaxis; none developed renal scaring.

  Our data suggest antibiotic resistant urinary tract isolates in children occur mainly in false positive urine samples and those on antibiotic prophylaxis. Studies in adults have shown that trimethoprim resistance is independently associated with exposure to trimethoprim, antibiotics other than trimethoprim and prior UTI.[3,4] Ladhani and Gransden do not report if urine bags were used to collect specimens, nor how many antibiotic resistant urinary tract isolates were not genuine urine infections, nor which children were on prophylaxis or had had previous treatment for UTI.

  For the community isolates there is also a potential for bias. A recent New Zealand study concluded that “actual resistance rates are significantly less than those derived from routine pooled laboratory specimens, and when used in an intention to treat calculation to inform empiric prescribing, become even less significant”.[5] Many general practitioners (GPs) will not send a urine culture from a child with a suspected UTI. They may be more likely to send samples if the child fails to respond to empirical antibiotic treatment. This will thus falsely raise the proportion with antibiotic resistant isolates. GPs may also use urine bags leading to false positive results.

  2. Empiric use of nitrofurantoin. The suggestion that nitrofurantoin should be the first line empiric treatment for UTI in children should be reviewed. Children taking nitrofurantoin have significantly more adverse effects than those taking trimethoprim.[6] Nitrofurantoin needs to be taken 4 times a day, this is associated with lower adherence levels than regimens dosed once or twice daily.[7] Nitrofurantoin also costs about 60 times as much as trimethoprim or cefalexin.

  Unfortunately, no data is given on sensitivity to cefalexin. This antibiotic is commonly used for UTI, is cheap and has a very acceptable taste. This might be a better alternative should trimethoprim be inappropriate.

  Ladhani and Gransden have provided some useful data on antibiotic resistance. “While collection of these routine data is essential to provide early warning of emergent resistance, a truly representative rate should be determined to inform prescribing decisions if resistance appears to be increasing”.[5]

  Proper trials of empiric antibiotic treatment in children with UTI are required. Until these are done our experience shows that local audit of cases notes of children with antibiotic resistant urinary tract isolates is simple and helps provide data on which to base local antibiotic guidelines. I would encourage other units to do it.

  References

  (1) Downs SM. Technical Report: Urinary Tract Infections in Febrile Infants and Young Children. Pediatrics 1999;103(4).

  (2) Ferry S, Burman, LG, Holm SE. Clinical and bacteriological effects of therapy of urinary tract infection in primary health care: relation to in vitro sensitivity testing. Scandinavian Journal of Infectious Diseases 1988;20:535–44

  (3) Steinke DT, Seaton RA, Phillips G, MacDonald TM, Davey PG. Prior trimethoprim use and trimethoprim-resistant urinary tract infection: a nested case-control study with multivariate analysis for other risk factors. J Antimicrobial Chemotherapy 2001;47:781-787.

  (4) Sotto A, De Boever CM, Fabbro-Peray P, Gouby A, Sirot D, Jourdan J. Risk factors for antibiotic-resistant Escherichia coli isolated from hospitalized patients with urinary tract infections: a prospective study. J Clin Microbiol 2001;39:438-44.

  (5) Richards DA, Toop LJ, Chambers ST, Sutherland MG, Harris BH, Ikram RB, Jones MR, McGeoch GR, Peddie B. Antibiotic resistance in uncomplicated urinary tract infection: problems with interpreting cumulative resistance rates from local community laboratories. NZ Med J 2002;115:12-4.

  (6) Williams GJ, Lee A, Craig JC. Long-term antibiotics for preventing recurrent urinary tract infection in children. In: The Cochrane Library, Issue 4, 2001. Oxford: Update Software.

  (7) Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001;23:1296-310.

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  Conflict of Interest:
  None declared.

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