title: Effects of antibiotics on Shiga toxin 2 production and bacteriophage induction by epidemic Escherichia coli O104:H4 strain.
abstract: The role of antibiotics in treatment of enterohemorrhagic Escherichia 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 of stx(2)-harboring bacteriophages, stx(2) transcription, and Stx2 production in this emerging pathogen. Ciprofloxacin significantly increased stx(2)-harboring phage induction and Stx2 production in outbreak isolates (P values of <0.001 to <0.05), while fosfomycin, gentamicin, and kanamycin insignificantly influenced them (P > 0.1) and chloramphenicol, meropenem, azithromycin, rifaximin, and tigecycline significantly decreased them (P ≤ 0.05). Ciprofloxacin and chloramphenicol significantly upregulated and downregulated stx(2) transcription, respectively (P < 0.01); the other antibiotics had insignificant effects (P > 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 stx(2)-harboring phages nor increased stx(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.
authors.affiliation: Institute of Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, Münster, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Bielaszewska
authors.forename: Evgeny A
authors.initials: EA
authors.lastname: Idelevich
authors.forename: Wenlan
authors.initials: W
authors.lastname: Zhang
authors.forename: Andreas
authors.initials: A
authors.lastname: Bauwens
authors.forename: Frieder
authors.initials: F
authors.lastname: Schaumburg
authors.forename: Alexander
authors.initials: A
authors.lastname: Mellmann
authors.forename: Georg
authors.initials: G
authors.lastname: Peters
authors.forename: Helge
authors.initials: H
authors.lastname: Karch
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D001435:Bacteriophages / Q000187:drug effects*; D002701:Chloramphenicol / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism* / Q000821:virology; D000077731:Meropenem; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D012294:Rifamycins / Q000494:pharmacology; D000078262:Rifaximin; D022641:Shiga Toxin 2 / Q000378:metabolism*; D013845:Thienamycins / Q000494:pharmacology; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D012294:Rifamycins; D022641:Shiga Toxin 2; D013845:Thienamycins; D002939:Ciprofloxacin; D002701:Chloramphenicol; D000078304:Tigecycline; D017963:Azithromycin; D000077731:Meropenem; D008911:Minocycline; D000078262:Rifaximin