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Review
. 2016 May 15;62(10):1251-1258.
doi: 10.1093/cid/ciw099. Epub 2016 Feb 24.

Shiga Toxin-Producing Escherichia coli Infection, Antibiotics, and Risk of Developing Hemolytic Uremic Syndrome: A Meta-analysis

Stephen B Freedman  1   2 , Jianling Xie  2 , Madisen S Neufeld  2 , William L Hamilton  3 , Lisa Hartling  4 , Phillip I Tarr  5 ; Alberta Provincial Pediatric Enteric Infection Team (APPETITE); Alberto Nettel-Aguirre, Anderson Chuck, Bonita Lee, David Johnson, Gillian Currie, James Talbot, Jason Jiang, Jim Dickinson, Jim Kellner, Judy MacDonald, Larry Svenson, Linda Chui, Marie Louie, Martin Lavoie, Mohamed Eltorki, Otto Vanderkooi, Raymond Tellier, Samina Ali, Steven Drews, Tim Graham, Xiao-Li Pang
Affiliations
Review

Shiga Toxin-Producing Escherichia coli Infection, Antibiotics, and Risk of Developing Hemolytic Uremic Syndrome: A Meta-analysis

Stephen B Freedman et al. Clin Infect Dis. .

Abstract

Background: Antibiotic administration to individuals with Shiga toxin-producing Escherichia coli (STEC) infection remains controversial. We assessed if antibiotic administration to individuals with STEC infection is associated with development of hemolytic uremic syndrome (HUS).

Methods: The analysis included studies published up to 29 April 2015, that provided data from patients (1) with STEC infection, (2) who received antibiotics, (3) who developed HUS, and (4) for whom data reported timing of antibiotic administration in relation to HUS. Risk of bias was assessed; strength of evidence was adjudicated. HUS was the primary outcome. Secondary outcomes restricted the analysis to low-risk-of-bias studies employing commonly used HUS criteria. Pooled estimates of the odds ratio (OR) were obtained using random-effects models.

Results: Seventeen reports and 1896 patients met eligibility; 8 (47%) studies were retrospective, 5 (29%) were prospective cohort, 3 (18%) were case-control, and 1 was a trial. The pooled OR, including all studies, associating antibiotic administration and development of HUS was 1.33 (95% confidence interval [CI], .89-1.99; I(2) = 42%). The repeat analysis including only studies with a low risk of bias and those employing an appropriate definition of HUS yielded an OR of 2.24 (95% CI, 1.45-3.46; I(2) = 0%).

Conclusions: Overall, use of antibiotics was not associated with an increased risk of developing HUS; however, after excluding studies at high risk of bias and those that did not employ an acceptable definition of HUS, there was a significant association. Consequently, the use of antibiotics in individuals with STEC infections is not recommended.

Keywords: Escherichia coli; Shiga toxin; antibiotics; hemolytic uremic syndrome; meta-analysis.

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Figures

Figure 1.
Figure 1.
Selection of studies for inclusion in the meta-analysis. Abbreviations: CINAHL, Cumulative Index of Nursing and Allied Health Literature; PICO, P - patient, problem or population, I - intervention, C - comparison, control or comparator, O - outcomes.
Figure 2.
Figure 2.
Random-effects meta-analysis of studies comparing odds of developing hemolytic uremic syndrome (HUS) in patients with Escherichia coli infection treated with antibiotics compared to those who did not receive antibiotics. The term “favors no antibiotics” implies that when antibiotics were given to the patients with Shiga toxin–producing Escherichia coli (STEC) infection, we observed increased odds of developing HUS, and the term “favors antibiotics” implies that when antibiotics were given to the patients with STEC infection, we observed decreased odds of developing HUS. Abbreviations: CI, confidence interval; M-H, Mantel–Haenszel.
Figure 3.
Figure 3.
Random-effects meta-analysis of studies comparing odds of developing hemolytic uremic syndrome (HUS) including only studies deemed to be of low risk of bias and meeting HUS definition. The term “favors no antibiotics” implies that when antibiotics were given to the patients with Shiga toxin–producing Escherichia coli (STEC) infection, we observed increased odds of developing HUS, and the term “favors antibiotics” implies that when antibiotics were given to the patients with STEC infection, we observed decreased odds of developing HUS. Abbreviations: CI, confidence interval; M-H, Mantel–Haenszel.
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