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The role of antibiotics in treatment of enterohemorrhagicEscherichia coli (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 ofstx 2 -harboring bacteriophages,stx 2 transcription, and Stx2 production in this emerging pathogen. Ciprofloxacin significantly increasedstx 2 -harboring phage induction and Stx2 production in outbreak isolates (P values of &lt;0.001 to &lt;0.05), while fosfomycin, gentamicin, and kanamycin insignificantly influenced them (P &gt; 0.1) and chloramphenicol, meropenem, azithromycin, rifaximin, and tigecycline significantly decreased them (P ≤ 0.05). Ciprofloxacin and chloramphenicol significantly upregulated and downregulatedstx 2 transcription, respectively (P &lt; 0.01); the other antibiotics had insignificant effects (P &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 inducedstx 2 -harboring phages nor increasedstx 2 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.

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