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Developing a novel therapy for neonatal sepsis

Knight, Breanna (2019) Developing a novel therapy for neonatal sepsis. Honours thesis, Murdoch University.

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Preterm infants are highly susceptible to neonatal sepsis with substantial morbidity and mortality. Early empiric treatment is mandatory as blood culture results take up to 48 hours. Empirical treatment is ineffective if the wrong pathogen is targeted. Antimicrobial peptide IDR1018 is a novel adjuvant antimicrobial with broad activity. IDR1018 may synergise with common neonatal antibiotics. Antibacterial checkerboard assays were performed of IDR1018 and the neonatal antibiotics vancomycin or gentamicin against prototypical neonatal pathogens. Standard testing conditions used RPMI1640 + 5% Luria Bertani broth. Further, time-to-kill assays were performed with samples taken at 0, 2, 4 and 24 hours to determine the effectiveness and kinetics of the drug combination in adult human serum, and compared against individual antibiotics or IDR1018 only and the empiric combination of gentamicin and vancomycin. Synergy was observed between vancomycin and IDR1018 against 3 clinical isolates of E. coli and 1 ATCC strain using the Fractional Inhibitory Concentration Index. No synergistic activity was observed in human serum IDR1018 and vancomycin against E. coli and S. aureus. IDR1018 had minimal activity against the bacteria independently. IDR1018 was inactive against E. coli and S. aureus in human serum at the synergistic dose, suggesting that at low levels of the antimicrobial peptide there is a component of the serum inhibiting its activity. When the human serum was heat treated, synergy between IDR1018 and vancomycin against E. coli and S. aureus was restored. Further tests are required to find the component of the serum that is inhibiting activity, such as denaturing the proteins in the serum before repeating the time-to-kill assay, or attempting to increase the level of free IDR1018 in the serum by raising the IDR1018 dose.

Item Type: Thesis (Honours)
Murdoch Affiliation(s): Medical, Molecular and Forensic Sciences
United Nations SDGs: Goal 3: Good Health and Well-Being
Supervisor(s): Currie, Andrew, Strunk, Tobias, Abraham, Sam and Abraham, Rebecca
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