Antibiotic Resistance in Pediatric E. coli Urinary Tract Infections
Abstract & Commentary
Synopsis: Risk factors for antimicrobial resistance among E. coli UTIs were identified in a population of children seen at a tertiary care center in Ontario over a two-year period. Increasing resistance of E. coli to common, inexpensive, and well-tolerated antibiotics was noted and their use as prophylactic agents should be re-examined.
Source: Allen UD, et al. Risk factors for resistance to "first-line" antimicrobials among urinary tract isolates of Es-cherichia coli in children. CMAJ 1999;160:1436-1440.
Allen and colleagues studied 1636 consecutive Escherichia coli isolates from 967 children with urinary tract isolates (UTI) at a children’s hospital in Canada over a two-year period (1992-1994). Their goal was to determine the prevalence of resistance to commonly used antibiotics for treatment of UTI and to identify risk factors associated with this resistance. Risk factors were identified using a case-control study in which 274 children with E. coli resistant to trimethoprim-sulfamethoxazole (Tmp-Smx) were matched with children with Tmp-Smx-sensitive isolates.
There was a disturbingly high prevalence of resistance among E. coli isolates to ampicillin (45%) and Tmp-Smx (31%) and to both ampicillin and Tmp-Smx (22%). As expected, resistance to nitrofurantoin (2%), gentamicin (3%), and cefotaxime (0.1%) was much less. Approximately 1.7% of the isolates were resistant to both ampicillin and gentamicin, which, as Allen et al point out, may begin to have implications in the choice of empiric antibiotic therapy for neonatal sepsis in their population.
Risk factors for antibiotic resistance included: 1) antibiotic treatment for more than four weeks in the preceding six months (OR*14); 2) the presence of urinary tract abnormalities including vesicoureteral reflux (OR 4); 3) hospitalization within the past year (OR 2-4); 4) the presence of a malignant disease (OR 5); 5) antibiotic prophylaxis for immunodeficiency (OR 15); and 6) older age, since children younger than 2 years were three times less likely to be infected with resistant organisms. The incidence of pyelonephritis was not greater in the Tmp-Smx-resistant group.
Allen et al conclude that the role of commonly used, inexpensive antibiotics such as ampicillin and Tmp-Smx in the outpatient treatment and prevention of urinary tract infections requires re-examination, particularly in children who have recently received antibiotic therapy.
Comment by Thomas L. Kennedy, MD, FAAP
We are all concerned about the growing problem of antimicrobial resistance spurred on by the extensive use, and sometimes overuse, of antibiotics. Knowing the magnitude of the problem for a given locale can be helpful in the choice of antibiotics. Additionally, however, identifying other risk factors can assist not only in the selection of antibiotics, but also in the development of strategies to avoid antibiotic use in certain populations if possible. For years, we have worried that the administration of "first-line" drugs such as amoxicillin for prophylaxis might lead to resistance as a result of antimicrobial pressure. The finding that four or more weeks of antibiotic use in the preceding six-month period is associated with resistance appears to support that concern. The other risk factors listed above are not surprising and make sense: things such as being in the hospital, having an immuno-deficiency, or being younger and not having been treated with many courses of antibiotics. The absence of an association with pyelonephritis is somewhat surprising because, at least simplistically, one often equates more aggressive with more resistant organisms.
The findings in this study suggest that the use of nitrofurantoin, which has a low rate of resistance by E. coli, continues to be a good choice for urinary tract prophylaxis. It is, after all, safe, effective, and inexpensive. Unfortunately, it is not a favorite, either for parents or children, in terms of taste and acceptability, but you can’t have everything. Other approaches, such as alternating antibiotics, may also demonstrate effectiveness and should be studied further. (Dr. Kennedy is Associate Clinical Professor of Pediatrics, Yale University School of Medicine.)
*(OR = odds ratio, or the odds of having the risk factor if the condition [e.g., Tmp-Smx resistance] is present divided by the odds of having the risk factor if the condition is not present.)
16. Risk factors for Tmp/Smx antibiotic resistance of cultured E. coli include all of the following except:
a. age older than 6 years.
b. antibiotic treatment for more than four weeks in the preceding six months.
c. a history of pyelonephritis.
d. grade 4 vesico-ureteral reflux.
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