Source: Smith KE, Wilker PR, Reiter PL, et al. Antibiotic treatment of Escherichia coli O157 infection and the risk of hemolytic uremic syndrome, Minnesota. Pediatr Infect Dis J. 2012;31(1):37-41; doi:10.1097/INF.0b013e31823096a8. See AAP Grand Rounds commentary by Dr. Robert Tolan, Jr. (subscription required).
PICO
Question: Among Minnesota residents <20 years old with Escherichia coli O157 infection, does antibiotic treatment increase the risk of progression to hemolytic uremic syndrome?
Question type: Intervention
Study design: Age-matched, case-control comparison
A primary care practitioner called me recently to ask about a 3 year old child with bloody diarrhea and a stool culture positive for Shiga toxin, the presumptive cause of hemolytic uremic syndrome (HUS). He wanted to know risks and benefits of antibiotic treatment in this situation. This study from the Minnesota Department of Health adds to our understanding of management issues, but it's by no means the last word on the subject.
This is not a typical case-control study; both groups consisted of children with E. coli O157 infection, and the comparison groups were actually those who received antibiotics versus those who did not. So, the authors (or perhaps the journal editors) have designated it a "case-case" comparison study. They found that HUS patients were more likely to have received bactericidal antibiotics within the first three days of diarrhea.
In the hierarchy of study design, which is simply a rating that points to the likelihood of the study results subsequently being shown to be wrong, case-control studies rank below randomized controlled trials. Prior cohort or case-control studies have found conflicting results for antibiotic treatment association with HUS.
At the moment, we must deal with less than optimal data on which to base a decision to use antibiotic treatment for a child with diarrhea caused by a Shiga toxin-producing organism. The tough decision, as mentioned by Dr. Tolan in his commentary, is that initially these cases resemble shigellosis, where early antibiotic treatment might be beneficial and at least could limit duration of contagion.
My inclination now is to withhold therapy for most cases, because of this study and others that tend to support the hypothesis that antibiotic treatment could result in increased toxin release and therefore contribute to HUS development. However, I won't be surprised if I'm proven wrong in the future.
Sunday, May 13, 2012
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The issue of the empiric administration of antimicrobials to persons with bloody (invasive)or STEC diarrhea is fervently debated in the infectious disease community. It is very important to note the wide confidence intervals in the analyses. Furthermore, although bactericidal and beta-lactam antibiotics appeared to have been consumed by persons who developed HUS, we cannot generalize these findings to all antimicrobials. It is worth noting the March 2012 JAMA article (JAMA, March 14, 2012—Vol 307, No. 10) by German authors who did not note a predisposition to HUS in persons who received azithromycin as a prophylaxis against meningitis in persons receiving an immunomodulating agent. Furthermore, stool shedding of the STEC (E. coli 0104) was decreased in those receiving azithromycin. As clinicians, we must be cautious not to generalize the results found for specific antimicrobials to all agents and should remain aware that in certain situations, empiric antimicrobial treatment may be indicated.
ReplyDeleteDr. Shane (for those of you who don't know, she is a pediatric infectious disease physician and research at Emory University) makes a very important point here, that not all antibiotics are created equally. This is certainly true in the study by Smith, et al. The JAMA study Dr. Shane refers to came about from the unusual outbreak of HUS associated with a novel E. coli strain, serotype O104:H4, likely associated with contaminated sprouts. It was basically an observational study, with some patients receiving a monoclonal antibody, eculizumab, that blocks terminal complement pathway activation. It's hard to know how to translate this to patients who might develop HUS but do not receive eculizumab.
ReplyDeleteThe JAMA article, as well as the detective stories about the German outbreak (see NEJM 2011; 365:1763-70 and 1771-80) make for interesting reading.