Non-antibiotic strategies for sepsis

Sepsis and septic shock remain a considerable therapeutic challenge. Despite significant advances in supportive care and the availability of potent, broad-spectrum antibiotics, the overall mortality due to sepsis is still approximately 35%, and this increases to 60% if patients develop septic shock. Antibiotics constitute a necessary part of the treatment of sepsis, and there is probably considerable scope to improve the way in which they are used. Nevertheless, antibiotics alone, even used optimally, are probably not sufficient to substantially reduce the mortality that accompanies the multiorgan failure that occurs in septic patients. For this reason, considerable efforts have been expended in developing non-antibiotic (or so-called adjunctive) forms of treatment, and here the general approaches to these types of treatment are reviewed. There are three main categories: improvements in supportive care, treatments aimed at bacterial virulence factors, and treatments aimed at host mediators. This is not intended to be a comprehensive review, but rather to provide examples in each category to illustrate the general principles-and the hurdles-that have characterized these approaches to therapy.