Modified poly(L-lysine)-based structures as novel antimicrobials for diabetic foot infections, an in-vitro study [version 1; peer review: 2 approved]

Background: Wound infections occur as sequelae to skin trauma and cause significant hospitalizations, morbidity and mortality. Skin traumas arise more frequently in those with diabetes or cardiovascular disease and in these settings, may be chronic with poorer outcomes including lower limb amputation. Treatment of chronic wound infection is challenging due to antibiotic resistance and biofilm formation by bacteria including S. aureus and P. aeruginosa, which are among the most frequent causative pathogens. Managing these challenging infections requires new molecules and modalities.  Methods: We evaluated antimicrobial and anti-biofilm activity of star-shaped poly(L-lysine) (PLL) polymers against S. aureus and P. aeruginosa strains and clinical isolates recovered from wounds including diabetic foot wounds (DFW) in a Dublin Hospital in 2019. A star-shaped PLL polypeptide series, specifically G2(8)PLL 20, G3(16)PLL 10, G4(32)PLL 5 with variation in polypeptide chain length and arm-multiplicity, were compared to a linear peptide, PLL 160 with equivalent number of lysine residues.  Results: All PLLs, including the linear polypeptide, were bactericidal at 1μM against S. aureus 25923 and P. aeruginosa PAO1, with log reduction in colony forming units/ml between 2.7-3.6. PLL 160 demonstrated similar killing potency against 20 S. aureus and five P. aeruginosa clinical isolates from DFW, mean log reductions: 3.04 ± 0.16 and 3.96 ± 0.82 respectively after 1 hour incubation. Potent anti-biofilm activity was demonstrated against S. aureus 25923 but for clinical isolates, low to moderate loss of biofilm viability was shown using PLL 160 and G3(16)PLL 10 at 50 μM ( S. aureus) and 200 μM ( P. aeruginosa) with high inter-isolate variability . In the star-shaped architecture, antimicrobial activity was retained with incorporation of 5-mer hydrophobic amino-acid modifications to the arms of the polypeptides (series G3(16)PLL 20-coPLT 5, G3(16)PLL 20-coPLI 5, G3(16)PLL 20-coPLP 5).  Conclusion: These polypeptides offer structural flexibility for clinical applications and have potential for further development, particularly in the setting of diabetic foot and other chronic wound infections. </p

Home FIRsT: interdisciplinary geriatric assessment and disposition outcomes in the Emergency Department

Background: Older people in the Emergency Department (ED) are clinically heterogenous and some presentations may be better suited to alternative out-of-hospital pathways. A new interdisciplinary comprehensive geriatric assessment (CGA) team (Home FIRsT) was embedded in our acute hospital's ED in 2017.Aim: To evaluate if routinely collected CGA metrics were associated with ED disposition outcomes.Design: Retrospective observational study.Methods: We included all first patients seen by Home FIRsT between 7th May and 19th October 2018. Collected measures were sociodemographic, baseline frailty (Clinical Frailty Scale), major diagnostic categories, illness acuity (Manchester Triage Score) and cognitive impairment/delirium (4AT). Multivariate binary logistic regression models were computed to predict ED disposition outcomes: hospital admission; discharge to GP and/or community services; discharge to specialist geriatric outpatients; discharge to the Geriatric Day Hospital.Results: In the study period, there were 1,045 Home FIRsT assessments (mean age 80.1 years). For hospital admission, strong independent predictors were acute illness severity (OR 2.01, 95% CI 1.50-2.70, PConclusions: Routinely collected CGA metrics are useful to predict ED disposition. The ability of baseline frailty to predict ED outcomes needs to be considered together with acute illness severity and delirium.</p