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Choosing the optimal combination of antimicrobial peptides and antibiotics to treat acute sepsis

Whitehouse, Samuel (2017) Choosing the optimal combination of antimicrobial peptides and antibiotics to treat acute sepsis. Honours thesis, Murdoch University.

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Sepsis is an infection, usually bacterial, of normally sterile parts of the body and leads to systemic illness and a panoply of non-selective inflammatory responses that are nonspecific. Preterm neonates (infants born <37 weeks gestation) are particularly affected by sepsis with a prevalence up to 62%, particularly LOS acquired after 72 hours of life, caused from micro-organisms acquired either perinatally or postnatally usually as a consequence of nosocomial transmission. Increased antibiotic resistant bacteria prevalence has also made treating preterm sepsis more challenging thus new treatments are required to overcome the antibiotic resistance. Synergy between AMPs/antibiotics has been documented before but very few studies at present test various combinations of AMPs/antibiotics in human whole blood. This study set out to determine the optimum combination of AMPs, rBPI21, LF, IDR-1018 and LL-37, and antibiotics, Vancomycin and Ceftriaxone, to kill common sensitive and resistant preterm infant clinical isolate sepsis causing bacteria (S. aureus, MRSA, E. coli and ESBL E. coli), inoculated into donated healthy adult whole blood. This study showed that the Vancomycin and IDR-1018 combination was the only combination that had a significantly increased inhibitory effect, against E. coli despite the Vancomycin resistance of E. coli. This study also found that only IDR-1018 had any inhibitory activity against three of the four bacteria used (E. coli, MRSA and ESBL E. coli). We found that the endogenous levels of AMPs and immune cells in donor blood had no effect on the bacteria used in the study at the doses tested. To conclude, this study found a combination of AMPs/antibiotic that can potentially improve sepsis treatment in preterms. But more work is needed to ensure that this combination is a viable new treatment for preterm infant sepsis.

Item Type: Thesis (Honours)
Murdoch Affiliation(s): School of Veterinary and Life Sciences
United Nations SDGs: Goal 3: Good Health and Well-Being
Supervisor(s): Currie, Andrew, Abraham, Sam, Strunk, Tobias and Litton, Ed
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