Inadequate timing between corticosteroid and antibiotics applications increases mortality due to sepsis

This study tested the hypothesis that the use of corticosteroids prior to antibiotics can lower the mortality rate in severe infections by S. aureus or Gram-negative bacilli, using an animal model. This study was a prospective and controlled study, placed in a university laboratory. Seven hundred and sixty mice distributed into three groups (Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae infected). The interventions in each group were: I) infection control (intra-peritoneal); II) treatment solely with antibiotics (teicoplanin or amikacin); III) antibiotics administered prior to the corticosteroid (methylprednisolone); IV) antibiotics administered after the corticosteroid. Mortality in the E. coli group, subgroup I: 100%; subgroup II: 55% (p<0.001); subgroup III: 62.5% (p=0.2488, compared to subgroup II); subgroup IV: 20% (p<0.01 compared to subgroups II and III). Mortality in the K. pneumoniae group: subgroup I: 100%; subgroup II: 72.5% (p<0.01); subgroup III: 80% (p=0.215 compared to subgroup II); subgroup IV: 45% (p<0.01 compared to subgroups II and III). Mortality in the S. aureus group: subgroup I: 82.5%; II: 42.5% (p<0.001); subgroup III: 77.5% (p=0.2877 compared to subgroup I); subgroup IV: 32.5% (p=0.1792 compared to subgroup II). The use of corticosteroids prior to antibiotics lowered the mortality rate caused by Gram-negative bacteria and did not affect the mortality caused by S. aureus. When used after starting treatment with antibiotics, the corticosteroid was not superior to the use of antibiotics alone in the case of the Gram-negative bacteria, and was not significantly different from non-treatment of the infection, in the case of S. aureus.