Anti–Tumor Necrosis Factor Antibody Impairs the Therapeutic Effect of Ceftriaxone in Murine Pneumococcal Pneumonia

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.