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Table 3 Antimicrobial actions needed for increasing of sepsis therapy effectiveness

From: Sepsis: mechanisms of bacterial injury to the patient

Antimicrobials Needed actions and available agents and technologies
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.