title: Anti-tumor necrosis factor antibody impairs the therapeutic effect of ceftriaxone in murine pneumococcal pneumonia.
abstract: Treatments aimed at inhibition of tumor necrosis factor (TNF) in patients with sepsis have been unsuccessful. Up to 50% of such patients suffer from pneumonia. To determine the effect that treatment with anti-TNF has on pneumococcal pneumonia, mice were intranasally inoculated with Streptococcus pneumoniae and, 25 h later, treated with 1 of the following: (1) control antibody, (2) anti-TNF, (3) ceftriaxone (CEF) with control antibody, or (4) CEF with anti-TNF. In the absence of treatment with CEF, mice displayed high bacterial loads in lungs, and all of these mice died within 5 days after inoculation. Anti-TNF did not influence these outcomes. In contrast, 60% of mice treated with CEF alone survived. Anti-TNF administered together with CEF reduced survival to 40% and was associated with enhanced bacterial outgrowth. These data suggest that treatment with anti-TNF impairs the therapeutic efficacy of CEF during pneumococcal pneumonia.
authors.affiliation: Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, F4-222 Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. a.w.rijneveld@amc.uva.nl
authors.forename: Anita W
authors.initials: AW
authors.lastname: Rijneveld
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Peter
authors.initials: P
authors.lastname: Speelman
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D002443:Ceftriaxone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000473:pathology; D013296:Streptococcus pneumoniae; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000900:Anti-Bacterial Agents; D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D002443:Ceftriaxone