title: Peroral ciprofloxacin therapy impairs the generation of a protective immune response in a mouse model for Salmonella enterica serovar Typhimurium diarrhea, while parenteral ceftriaxone therapy does not.
abstract: Nontyphoidal Salmonella (NTS) species cause self-limiting diarrhea and sometimes severe disease. Antibiotic treatment is considered only in severe cases and immune-compromised patients. The beneficial effects of antibiotic therapy and the consequences for adaptive immune responses are not well understood. We used a mouse model for Salmonella diarrhea to assess the effects of per os treatment with ciprofloxacin (15 mg/kg of body weight intragastrically 2 times/day, 5 days) or parenteral ceftriaxone (50 mg/kg intraperitoneally, 5 days), two common drugs used in human patients. The therapeutic and adverse effects were assessed with respect to generation of a protective adaptive immune response, fecal pathogen excretion, and the emergence of nonsymptomatic excreters. In the mouse model, both therapies reduced disease severity and reduced the level of fecal shedding. In line with clinical data, in most animals, a rebound of pathogen gut colonization/fecal shedding was observed 2 to 12 days after the end of the treatment. Yet, levels of pathogen shedding and frequency of appearance of nonsymptomatic excreters did not differ from those for untreated controls. Moreover, mice treated intraperitoneally with ceftriaxone developed an adaptive immunity protecting the mice from enteropathy in wild-type Salmonella enterica serovar Typhimurium challenge infections. In contrast, the mice treated intragastrically with ciprofloxacin were not protected. Thus, antibiotic treatment regimens can disrupt the adaptive immune response, but treatment regimens may be optimized in order to preserve the generation of protective immunity. It might be of interest to determine whether this also pertains to human patients. In this case, the mouse model might be a tool for further mechanistic studies.
authors.affiliation: Institut für Mikrobiologie, Eidgenössische Technische Hochschule, Zurich, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Endt
authors.forename: Lisa
authors.initials: L
authors.lastname: Maier
authors.forename: Rina
authors.initials: R
authors.lastname: Käppeli
authors.forename: Manja
authors.initials: M
authors.lastname: Barthel
authors.forename: Benjamin
authors.initials: B
authors.lastname: Misselwitz
authors.forename: Marcus
authors.initials: M
authors.lastname: Kremer
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Hardt
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002443:Ceftriaxone / Q000008:administration & dosage* / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000627:therapeutic use; D015169:Colony Count, Microbial; D003967:Diarrhea / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005243:Feces / Q000382:microbiology; D007263:Infusions, Parenteral; D051379:Mice; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000276:immunology; D012720:Severity of Illness Index
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D002443:Ceftriaxone