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Risk of Hemolytic Uremic Syndrome After Antibiotic Treatment of Escherichia coli O157:H7 Enteritis:  A Meta-analysis

Nasia Safdar, MD; Adnan Said, MD; Ronald E. Gangnon, PhD; Dennis G. Maki, MD
JAMA. 2002;288(8):996-1001. doi:10.1001/jama.288.8.996.
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Published online

Context The use of antibiotics for treatment of Escherichia coli O157:H7 infection has become controversial since a recent small study found that it may increase the risk of hemolytic uremic syndrome (HUS). However, other larger studies have reported a protective effect or no association.

Objective To determine whether antibiotic therapy for E coli O157:H7 enteritis increases the risk of HUS.

Data Sources PubMed and MEDLINE computer searches were performed for studies published from January 1983 to February 2001 using the key words hemolytic uremic syndrome, risk factor, antibiotics, and Escherichia coli O157:H7. Reference lists of relevant publications were reviewed, and 12 experts in the field were contacted to identify additional reports. No language restrictions were applied to the search.

Study Selection Studies were included if they reported a series of patients with documented E coli O157:H7 enteritis, some of whom developed HUS; had clear definitions of HUS; and had adequate data delineating the relationship between antibiotic therapy and the occurrence of HUS. Nine of the 26 identified studies fulfilled these criteria.

Data Extraction Two authors (N.S. and A.S.) independently reviewed each report identified by the searches and recorded predetermined information relevant to the inclusion criteria. A pooled odds ratio was calculated using a fixed-effects model, with assessment of heterogeneity among the studies.

Data Synthesis The pooled odds ratio was 1.15 (95% confidence interval, 0.79-1.68), indicating that there does not appear to be an increased risk of HUS with antibiotic treatment of E coli O157:H7 enteritis. Incomplete reporting of data in individual studies precluded adjustment for severity of illness.

Conclusion Our meta-analysis did not show a higher risk of HUS associated with antibiotic administration. A randomized trial of adequate power, with multiple distinct strains of E coli O157:H7 represented, is needed to conclusively determine whether antibiotic treatment of E coli O157:H7 enteritis increases the risk of HUS.

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Figure 1. Relationship Between Antibiotic Therapy for Escherichia coli O157:H7 Enteritis and Risk of Hemolytic Uremic Syndrome
Graphic Jump Location
An odds ratio (OR) of greater than 1.0 (ln OR >0) suggests that antibiotic therapy is associated with an increased risk of hemolytic uremic syndrome, and an OR of less than 1.0 (ln OR <0) suggests a decreased risk. CI indicates confidence interval. Sizes of data markers are proportional to sample sizes of the studies.
Figure 2. Funnel Plot of Estimated Ln ORs From 9 Studies
Graphic Jump Location
Solid vertical line represents pooled estimated log odds ratio (OR) across the studies. Dotted lines represent 2 SE bounds around the pooled estimate. Studies are represented by their reference numbers.

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