Bridging the Gaps: Systems-level approaches to antimicrobial resistance
Proof of concept: Assessment of a polymer-based nanoparticulate system to enhance drug delivery of lactoferrin to prevent C. difficile infection
Tanya Monaghan (Medicine), Cameron Alexander (Pharmacy) and Sarah Kuehne (Life Sciences)
C. difficile infection (CDI) is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhoea, and is potentially fatal. C. difficile occurs mainly in elderly patients and other vulnerable groups, especially those who have been exposed to antibiotic treatment. 17% of patients who are diagnosed with CDI have died by day 30 after diagnosis (NHS, 2014).
The University of Nottingham’s researchers have recently demonstrated that bovine lactoferrin, a protein found in cow’s milk, is capable of preventing growth of C. difficile and inhibiting toxin production in in gut a model and in culture experiments (Chilton C et al. J Antimicrob Chemother, 2016). This proof of concept study aims to apply existing methods to conjugate bovine lactoferrin with synthetic polymers to make it more stable and increase the amount of time it can circulate in the human body without being degraded. Different types of lactoferrin-polymer formulations will then be tested and validated in batch cultures and the most appropriate formulation chosen for future testing. This will allow researchers to control and target the delivery of this therapeutic protein for the potential future treatment of C. difficile.
Though the NHS has dramatically reduced the number of patients suffering from CDI, current C. difficile infection treatment is complicated by the fact that the bacterium is becoming resistant to many different antibiotics. The Centers for Disease Control and Prevention (CDC) has recently declared C. difficile an urgent antibiotic resistance threat. The way in which we treat C. difficile with antibiotics is inducing susceptibility to infection, and furthering the development and selection of antibiotic-resistant strains of bacteria. C. difficile also appears to help other pathogens to acquire resistance genes, making other pathogenic bacteria more resistant to antibiotics. Novel non-antibiotic-based therapeutic and preventative strategies against C. difficile, such as that explored within this study, are particularly important in reducing antimicrobial resistance.
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