Introduction: Synthetic antimicrobial peptides are potential candidates as adjuncts to conventional antimicrobial therapy. Two such synthetic peptides, the innate defence regulator peptides (IDR)-1018 and IDR-HH2 have shown previous antimicrobial effectiveness against a range of organisms in vitro. However, this effectiveness has yet to be examined against neonatal pathogens. This study aims to test the microbicidal and immunomodulatory capacity of IDR-1018 and IDR-HH2 against the neonatal pathogens Staphylococcus. aureus (SA), Staphylococcus epidermidis (SE) and Escherichia coli (EC) in adult and preterm infant blood.
Methods: Adult blood and preterm infant blood were obtained from healthy participants. Fresh peripheral blood was challenged with live SA, SE and EC as well as purified lipopolysaccharide (LPS), in the presence or absence of IDR-1018 and IDR-HH2. Bacterial growth was assessed by quantitative culture. IL-6, TNF-a and Chemokine Ligand-2 (CCL2) were measured in culture supernatants by multiplex bead assay.
Results: Both IDR-1018 and IDR-HH2 displayed effective anti-infective activity in adult blood against SA, SE and EC. When tested in preterm blood, both peptides inhibited LPS-induced IL-6 and TNF-a production. The IDRs were most effective with respect to growth inhibition of SA and SE and uniquely inhibited SE-induced inflammatory cytokine production. Additionally, IDR-1018 synergistically induced CCL2 production after SE challenge.
Conclusion: IDR-1018 and IDR-HH2 both displayed anti-infective properties in preterm infant blood. The two IDRs were effective against the most common neonatal pathogens and significantly modulated the associated inflammatory response. IDR-1018 in particular, is a promising adjunct to conventional antimicrobial therapy for sepsis and warrants further pre-clinical testing.