The invention provides compositions and methods for the targeted bacteriostatic and antibacterial agents and for treatment of sepsis caused by infectious diseases, such as bacterial and fungal diseases. In one aspect, the invention provides methods and compositions for decreasing the levels of LPS in the circulation of an individual, e.g., a human patient with sepsis, e.g., gram negative septic shock. In one aspect, the invention is directed to chimeric proteins comprising the MD-2 polypeptide and an opsinizing agent, e.g., antibody Fc domains, or equivalent. In one aspect, the invention is directed to chimeric proteins comprising fragments or altered form of MD-2 polypeptide and an opsinizing agent, e.g., antibody Fc domains, or equivalent. The invention also provides pharmaceutical compositions comprising the chimeric polypeptides of the invention, and methods of making and using them, including methods for ameliorating or preventing sepsis. The invention also provides compositions for transfecting cells with nucleic acid comprising the mutant MD-2 proteins and/or the chimeric polypeptides of the invention.