In mechanically ventilated patients with severe community-acquired pneumonia, add-on therapy with trimodulin, a novel polyclonal antibody preparation, did not statistically significantly increase ventilator-free days (primary endpoint) vs. placebo. Exploratory post hoc analyses suggest reductions in mortality for trimodulin compared with placebo in subsets of patients with elevated C-reactive protein levels and/or reduced immunoglobulin M levels, and warrant investigation in a phase III study with a targeted patient population.