Table 3 Antimicrobial actions needed for increasing of sepsis therapy effectiveness

New antibiotics

Should be able to:

a. dissolve in bacterial polysaccharides (capsule, biofilm) – not available.

b. kill bacteria in the condition of low metabolic activity – not available.

c. penetrate erythrocyte membrane and accumulate inside erythrocytes – not available.

d. overcome bacterial adaptation and resistance – not available.

Exotoxin neutralizing compounds

Should be able to:

a. cross-react with more than one exotoxin (available agents: synthetic peptide 6343 and antibody to the 6348 peptide).

b. inhibit exotoxin production (available agents: synthesized α-globin chain peptides, synthetic variants of α-globin chain peptides, human defensins).

c. reduce toxic shock mortality by suppressing TNF-alpha (available agent: glycerol monolaurate (GML).

d. target exotoxins (available agents: recombinant monoclonal antibodies)

e. neutralize the activity of superantigens (available agent: polyspecific immunoglobulin G (IVIG).

Endotoxin neutralizing compounds

Should be able to:

a. neutralize endotoxins (available agents: peptides modified by lipophilic moieties and non-peptidic molecules, particularly lipopolyamines (synthetic peptides, based on the endotoxin-binding domains of natural binding proteins such as lactoferrin, Limulus anti-LPS factor, NK-lysin, cathelicidins).

b. neutralize TNF (available agent: anti-TNF antibodies).

c. endotoxin removal (available: extracorporeal endotoxin removal devices or endotoxoid based vaccines).

Bacterial capsule affecting agents

Should be able to:

inhibit tyrosine phosphatase (PTP) and a protein tyrosine kinase (available agent: Fascioquinol E).

Bacterial biofilm affecting agents

Should be able to:

a. inhibit biofilm formation and motility (available agents: brominated furanones, ursine triterpenes, corosolic acid, asiatic acid, 3-indolylacetonitrile; indole).

b. exhibit antimicrobial and antibiofilm properties (available agents: N-acyl homoserine lactones, cationic molecules with an excess of lysine and arginine residues, d-amino acids, monomeric trimethylsilane (TMS), 1-alkylquinolinium bromide ionic liquids).

c. affect integrity of biofilms by degrading nucleic acid scaffold components of the extracellular matrix (available agents: nucleases such as DNase and RNase).

d. target matrix-associated proteins (available agents: serine proteases).

e. degrade poly-N-acetylglucosamine (PNAG), a major polysaccharide component of many bacterial extracellular matrices (available agent: Dispersin B).

f. disperse biofilm (available agent: nitric oxide (NO).

Agents that inhibit and neutralize hemolysins

Should be able to:

a. inhibit the production of α-hemolysin (available agents: Totarol, cAMP).

b. bound to lipoteichoic acids (available agent: apolipophorin (ApoLp).

Agents that inhibie antioxidantenzymes

Should be able to:

a. inhibit superoxide dismutase (available agents: the manganese and zinc binding protein calprotectin (CP).

b. inhibit catalase – not available.

c. inhibit glutathione peroxidase – not available.

Agents of “Biological antibacterial weapon”

Bacteriophage therapy

Therapy by Bdellovibrio like organisms

Saccharomyces therapy

Technical devices for bacteria clearing from the bloodstream

Should be able to:

a. remove bacteria and their toxins (available technologies: micro-encapsulated albumin activated charcoal (ACAC), magnetic nanoparticles (MNPs) modified with bis-Zn-DPA, bacteria binding synthetic ligands, magnetic nanobeads coated with an engineered human opsonin—mannose-binding lectin (MBL), synthetic pyrolysed carbon monolith, venovenous hemofiltration (CVVHF) combined with plasmapheresis.