Preclinical trials support the potential of CIDEM-501-503 for treating microbial infections caused by multiresistant bacteria. The main results are shown below.

Evaluation of the in vitro antimicrobial effect against MDR and XDR:

• The values expressed in a lethal concentration of 90% bacterial growth (LC90) in the three sequences identified on clinical isolates multiresistant strains of ESKAPE group are in the order of micromolar (<15 µM).

Assessment on time kill:

• The new peptide entities possess shorter kinetics for in vitro bacterial ‘kill’ assays than conventional antibiotics to exert their bactericidal effect. That suggests an effective mechanism of action without involving metabolic pathways while reducing the possibility of the emergence of resistance mechanisms.

Evaluation of the neutralizing activity of LPS by the monocyte activation test:

• The new peptide entities have an inhibitory effect on the expression of IL-6 induced by LPS in a whole blood culture using the Monocyte Activation Test. This response provides competitive advantages in an infectious environment by controlling the inflammatory response. Synergistic effect evaluation:
• The combinations between the peptide entities included in the 3 SEQ show synergistic effects.
• All hybrid variants produce a synergistic antibacterial effect when combined with Meropenem against clinical isolates of Gram-negative Klebsiella pneumoniae and Gram-positive multi-antibiotic resistant Staphylococcus aureus.

Avoidance of pathogen´s resistance barriers

• The peptides were evaluated against resistant bacterial strains expressing blaKPC and blaNDM genes. Their sublytic concentrations (MIC/2 and MIC/8) did not influence the expression of these genes.
• Peptide variants modified with a decanoic acid towards the amino terminus showed that in sublytic concentrations (MIC/2 and MIC/4), these peptides could significantly decrease the expression of bla_KPC and bla_NDM.

Currently, CIDEM-501-503 is in the preclinical development phase for submission of an application for clinical trial authorization (CTA). Preclinical models should be completed for indications of acute lung injury induced by microbial pathogens:

• Evaluation of peptides in the skin abscesses as infection model with opportunistic Gram-negative (Pseudomonas aeruginosa) and Gram-positive MDR bacteria such as vancomycin and methicillin resistant´s Staphylococcus aureus (MRSA and VRSA, respectively) belonging to the ESKAPE group.
• Evaluation of peptides in murine models for acute pulmonary infection by Acinetobacter baumanni, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
• Pharmacokinetics and bioavailability of peptides in systemic administration.