Log reduction of multidrug-resistant Gram-negative bacteria by the neutrophil-derived recombinant bactericidal/permeability-increasing protein

Multidrug-resistant (MDR) Gram-negative bacterial infections are a serious and ever-increasing threat for which limited therapeutic options exist. The bactericidal/permeability-increasing protein (BPI) is a cationic, neutrophil-derived, lipopolysaccharide (LPS)-binding protein that binds to Gram-negative bacteria (GNB) and LPS via its lipid A region. A recombinant fragment, rBPI-21, was studied extensively in clinical trials for meningococcal disease in the 1990s and exhibited no significant safety issues. In this report, a dose-dependent 1-2 log reduction of MDR Pseudomonas and Acinetobacter after 1 h incubation with rBPI-21 using clinically achievable doses is described. Given the dearth of novel antimicrobials expected to emerge from the pharmaceutical pipeline in the near future, exploration of rBPI-21 to combat MDR GNB is now warranted.