Effects of Antibiotics on Shiga Toxin 2 Production and Bacteriophage Induction by Epidemic Escherichia coli O104:H4 Strain

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>The role of antibiotics in treatment of enterohemorrhagic<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Escherichia coli</jats:named-content>(EHEC) infections is controversial because of concerns about triggering hemolytic-uremic syndrome (HUS) by increasing Shiga toxin (Stx) production. During the recent large EHEC O104:H4 outbreak, antibiotic therapy was indicated for some patients. We tested a diverse panel of antibiotics to which the outbreak strain is susceptible to interrogate the effects of subinhibitory antibiotic concentrations on induction of<jats:italic>stx</jats:italic><jats:sub>2</jats:sub>-harboring bacteriophages,<jats:italic>stx</jats:italic><jats:sub>2</jats:sub>transcription, and Stx2 production in this emerging pathogen. Ciprofloxacin significantly increased<jats:italic>stx</jats:italic><jats:sub>2</jats:sub>-harboring phage induction and Stx2 production in outbreak isolates (<jats:italic>P</jats:italic>values of &lt;0.001 to &lt;0.05), while fosfomycin, gentamicin, and kanamycin insignificantly influenced them (<jats:italic>P</jats:italic>&gt; 0.1) and chloramphenicol, meropenem, azithromycin, rifaximin, and tigecycline significantly decreased them (<jats:italic>P</jats:italic>≤ 0.05). Ciprofloxacin and chloramphenicol significantly upregulated and downregulated<jats:italic>stx</jats:italic><jats:sub>2</jats:sub>transcription, respectively (<jats:italic>P</jats:italic>&lt; 0.01); the other antibiotics had insignificant effects (<jats:italic>P</jats:italic>&gt; 0.1). Meropenem, azithromycin, and rifaximin, which were used for necessary therapeutic or prophylactic interventions during the EHEC O104:H4 outbreak, as well as tigecycline, neither induced<jats:italic>stx</jats:italic><jats:sub>2</jats:sub>-harboring phages nor increased<jats:italic>stx</jats:italic><jats:sub>2</jats:sub>transcription or Stx2 production in the outbreak strain. These antibiotics might represent therapeutic options for patients with EHEC O104:H4 infection if antibiotic treatment is inevitable. We await further analysis of the epidemic to determine if usage of these agents was associated with an altered risk of developing HUS.</jats:p>

Shiga Toxin–ProducingEscherichia coliInfection, Antibiotics, and Risk of Developing Hemolytic Uremic Syndrome: A Meta-analysis

“…We additionally explored antibiotic class as a risk factor in our meta-analysis; no antibiotic/antibiotic class emerged as protective from the development of HUS, compared with nontreatment [25,27]. Although there are intra-and interserotype differences in the release of Shiga toxin from STEC after exposure to antibiotics in vitro [43], the decision to treat must be made at the time of initial presentation; hence, the variable release of toxin by an infecting strain cannot, for the foreseeable future, be entered into clinical decisions. Moreover, when O157:H7 is analyzed separately from non-O157:H7 strains, the OR CIs are overlapping.…”

Molecular Aspects of Effect of Shiga Toxin in Humans - A Review

“…It is reported that about 12% risk of mortality is associated with the end-stage renal disease with STEC-HUS is and 25% of survivors experience long-term chronic kidney diseases including decreased glomerular filtration rate, proteinuria and hypertension (Zoja et al, 2010;Rosales et al, 2012). Antibiotic treatment is generally discouraged because of the potential to enhance the synthesis and release of Stx from EHEC and worsen disease severity Recent investigations suggest that the antibiotic ciprofloxacin increases Stx2 production in case of E. coli O104:H4 infection, while other antibiotics either suppress or do not affect toxin expression (Bielaszewska et al, 2012).…”

An Important Approach for Control of Enterohaemorrhagic Escherichia coli by Identification of Contaminating Sources in Beef Production Line

“…Among the major food borne pathogens, Enterohaemorrhagic Escherichia coli (EHEC) is one of the most important bacteria when beef production line is considered. The strains of EHEC are unusually virulent because of its low infectious dose, severe consequences of infection like haemorrhagic colitis and hemolytic uremic syndrome in humans, low acid tolerance, biofilm formation and antibiotic induced toxin release (Wells et al, 1983;Tarr et al, 1990;Benjamin and Datta, 1995;Hood and Zottola, 1997;Tuttle et al, 1999;Bielaszewska et al, 2012). Humans generally get infection by direct contact with carriers, their faeces, and contaminated soil and water.…”