Shiga toxin-induced haemolytic uraemic syndrome and the role of antibiotics: a global overview

Loukas Kakoullis; Eleni Papachristodoulou; Paraskevi Chra; George Panos

doi:10.1016/j.jinf.2019.05.018

Shiga toxin-induced haemolytic uraemic syndrome and the role of antibiotics: a global overview

J Infect. 2019 Aug;79(2):75-94. doi: 10.1016/j.jinf.2019.05.018. Epub 2019 May 28.

Authors

Loukas Kakoullis¹, Eleni Papachristodoulou¹, Paraskevi Chra², George Panos³

Affiliations

¹ Department of Internal Medicine, Nicosia General Hospital, University of Cyprus Medical School, Nicosia, Cyprus; Department of Respiratory Medicine, Patras University General Hospital, University of Patras School of Medicine, Patras, Greece.
² Department of Microbiology, Korgialenio-Benakio Red Cross Hospital, Athens, Greece.
³ Department of Internal Medicine, Section of Infectious Diseases, Patras University General Hospital, University of Patras School of Medicine, Patras, Greece; Department of Internal Medicine, Nicosia General Hospital, University of Cyprus Medical School, Nicosia, Cyprus. Electronic address: george.panos.frcp@gmail.com.

PMID: 31150744
DOI: 10.1016/j.jinf.2019.05.018

Abstract

Objectives: The administration of antibiotics in infections caused by Shiga toxin producing E. coli (STEC) strains, such as O157:H7, was and remains controversial, as it has been associated with the development of haemolytic uraemic syndrome (HUS). We conducted a literature review to better examine this association.

Methods: We searched the PubMed and Google Scholar databases for relevant articles, using the key words: ``haemolytic uraemic syndrome'', ``Shiga toxin'', ``E. coli O157:H7'', ``E. coli O104:H4'', ``STEC colitis'', ``STEC antibiotics'', ``STEC fosfomycin'', ``STEC trimethoprim sulfamethoxazole'', ``STEC fluoroquinolones'', ``STEC ciprofloxacin'', ``STEC rifaximin'', ``STEC gentamycin'', ``STEC colistin'', "Shiga toxin binding agent", "Shiga toxin monoclonal antibody" and ``STEC Japan epidemic''.

Results: Numerous studies report that antibiotics increase the risk of HUS development, while others report that antibiotics do not have any effect or can even reduce the rate of HUS development in STEC infections. The infecting STEC strain, the type of antibiotic as well as the timing of its administration appear to significantly affect the development of HUS in a STEC infected patient.

Conclusions: It appears that, while some antibiotics such as b-lactams and TMP/SMX may be detrimental, others appear to be safe and can prevent the development of HUS. Of note, fosfomycin appears to be the antibiotic with the most positive results from clinical studies, and may be able to avert HUS development, especially if administered within the first two or three days from diarrhoea onset. Fluoroquinolones have also shown positive outcomes in clinical studies, despite demonstrating unfavourable results in in vitro studies. Other agents, such as colistin, gentamycin and rifamycins, have shown promising results in in vitro studies and require further evaluation.

Keywords: Antibiotics; E. coli O104:H4; E. coli O157:H7; Fosfomycin; Haemolytic uraemic syndrome; Shiga toxin; Shiga toxin producing E. coli.

Publication types

Meta-Analysis
Review

MeSH terms

Anti-Bacterial Agents / administration & dosage
Anti-Bacterial Agents / adverse effects*
Anti-Bacterial Agents / therapeutic use
Clinical Studies as Topic
Disease Susceptibility*
Escherichia coli Infections / drug therapy
Escherichia coli Infections / microbiology
Escherichia coli O157 / drug effects
Escherichia coli O157 / physiology
Hemolytic-Uremic Syndrome / etiology*
Humans
Microbial Sensitivity Tests
Risk Factors
Shiga Toxin / adverse effects*
Shiga-Toxigenic Escherichia coli / drug effects
Shiga-Toxigenic Escherichia coli / physiology
Treatment Outcome

Substances

Anti-Bacterial Agents
Shiga Toxin