Porphyrin-Polymer as a Photosensitizer Prodrug for Antimicrobial Photodynamic Therapy and Biomolecule Binding Ability.

This study presents the development and characterization of a novel porphyrin-Jeffamine polymer conjugate designed to function as a photosensitizer prodrug for antimicrobial photodynamic therapy (aPDT). The conjugate features a photosensitive porphyrin unit covalently attached to a biocompatible polymer backbone, with enhanced solubility, stability, and bioavailability compared to those of the free porphyrin derivatives. The photophysical properties were studied using transient absorption spectroscopy spanning the fs-μs time scales in addition to emission studies.

Shear-Thinning Extrudable Hydrogels Based on Star Polypeptides with Antimicrobial Properties.

Hydrogels with low toxicity, antimicrobial potency and shear-thinning behavior are promising materials to combat the modern challenges of increased infections. Here, we report on 8-arm star block copolypeptides based on poly(L-lysine), poly(L-tyrosine) and poly(S-benzyl-L-cysteine) blocks. Three star block copolypeptides were synthesized with poly(S-benzyl-L-cysteine) always forming the outer block.

Improving the Management and Treatment of Diabetic Foot Infection: Challenges and Research Opportunities.

Diabetic foot infection (DFI) management requires complex multidisciplinary care pathways with off-loading, debridement and targeted antibiotic treatment central to positive clinical outcomes. Local administration of topical treatments and advanced wound dressings are often used for more superficial infections, and in combination with systemic antibiotics for more advanced infections. In practice, the choice of such topical approaches, whether alone or as adjuncts, is rarely evidence-based, and there does not appear to be a single market leader.

Modified poly(L-lysine)-based structures as novel antimicrobials for diabetic foot infections, an study.

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 and which are among the most frequent causative pathogens.

Three-dimensionally printable shear-thinning triblock copolypeptide hydrogels with antimicrobial potency.

Through rational design, block sequence controlled triblock copolypeptides comprising cysteine and tyrosine as well as a lysine or glutamic acid central block are devised. In these copolypeptides, each block contributes a specific property to the hydrogels to render them extrusion printable and antimicrobial. Three-dimensional (3D) printing of complex hydrogel structures with high shape retention is demonstrated.

Antimicrobial and degradable triazolinedione (TAD) crosslinked polypeptide hydrogels.

Hydrogels are perfectly suited to support cell and tissue growth in advanced tissue engineering applications as well as classical wound treatment scenarios. Ideal hydrogel materials for these applications should be easy to produce, biocompatible, resorbable and antimicrobial. Here we report the fabrication of degradable covalent antimicrobial lysine and tryptophan containing copolypeptide hydrogels, whereby the hydrogel properties can be independently modulated by the copolypeptide monomer ratio and chiral composition.

Exploiting a Neutral BODIPY Copolymer as an Effective Agent for Photodynamic Antimicrobial Inactivation.

We report the synthesis and photophysical properties of a neutral BODIPY photosensitizing copolymer (poly-8-(4-hydroxymethylphenyl)-4,4-difluoro-2,6-diethynyl-4-bora-3a,4a-diaza--indacene) containing ethynylbenzene links between the BODIPY units. The copolymer absorbs further towards the red in the UV-vis spectrum compared to the BODIPY precursor. Photolysis of the polymer produces a singlet excited state which crosses to the triplet surface in less than 300 ps.

Investigation of the Physical, Chemical and Microbiological Stability of Losartan Potassium 5 mg/mL Extemporaneous Oral Liquid Suspension.

Extemporaneous oral liquid preparations are commonly used when there is no commercially available dosage form for adjustable dosing. In most cases, there is a lack of stability data to allow for an accurately assigned shelf life and storage conditions to give greater confidence of product safety and efficacy over its shelf life. The aim of this study was to evaluate the physical, chemical and microbiological stability of an extemporaneous oral liquid suspension of losartan potassium, 5 mg/mL, used to treat paediatric hypertension in Our Lady's Children's Hospital Crumlin, Ireland.

Screening the nose, throat and the naso-pharynx for methicillin-resistant : a pilot study.

Patients who carry nasal methicillin-resistant (MRSA) may also harbour MRSA in the oro-pharyngeal cavity. However, the naso-oro-pharyngeal co-carriage is infrequently assessed. The incidence of concurrent MRSA carriage of the naso-oro-pharynx was ascertained, and the sensitivity of two methods, a throat swab and a phosphate buffered saline (PBS) oral rinse, for MRSA detection was investigated.

Photo-activated CO-release in the amino tungsten Fischer carbene complex, [(CO)WC(NCH)Me], picosecond time resolved infrared spectroscopy, time-dependent density functional theory, and an antimicrobial study.

Picosecond time-resolved infrared spectroscopy was used to probe the photo-induced early state dynamics preceding CO loss in the Fischer carbene complex, [(CO)WC(NCH)CH]. Time-dependent density functional theory calculations were employed to help in understanding the photochemical and photophysical processes leading to CO-loss. Electrochemical initiated CO release was quantified using gas chromatography.

Synthesis and characterisation of Co(iii) complexes of N-formyl hydroxylamines and antibacterial activity of a Co(iii) peptide deformylase inhibitor complex.

The X-ray crystal structure and pKa values of GSK322, a well-known and effective peptide deformylase inhibitor and antibacterial drug candidate, are reported. The first examples of Co(iii) complexes of N-formyl hydroxylamines are reported. Reaction of N-hydroxy-N-phenylformamide (HFA) with [Co(tren)Cl2]Cl and [Co(tpa)Cl2]Cl (where tren = tris(2-aminoethyl)amine, tpa = tris(2-pyridylmethyl)amine) with one equivalent of NaOH in H2O afforded [Co(tren)(HFA-1H)](PF6)1.

Vibrating Mesh Nebulisation of Pro-Antimicrobial Peptides for Use in Cystic Fibrosis.

Background: There has been considerable interest in the use of antimicrobial peptides (AMPs) as antimicrobial therapeutics in many conditions including cystic fibrosis (CF). The aim of this study is to determine if the prodrugs of AMPs (pro-AMPs) can be delivered to the lung by a vibrating mesh nebuliser (VMN) and whether the pro-AMP modification has any effect on delivery.

Methods: Physical characteristics of the peptides (AMP and pro-AMP) and antimicrobial activity were compared before and after nebulisation.

Molecular Characterization of Nasal Methicillin-Resistant Staphylococcus aureus Isolates Showing Increasing Prevalence of Mupirocin Resistance and Associated Multidrug Resistance following Attempted Decolonization.

Sequential methicillin-resistant (MRSA) isolates from patients following attempted mupirocin nasal decolonization showed an increase in mupirocin resistance (MR) from 6.6% to 20%. MR isolates from patients who failed decolonization yielded indistinguishable types and carried multiple antimicrobial and antiseptic resistance genes, which may guide infection control and prevention.

Action of antimicrobial peptides and their prodrugs on model and biological membranes.

Antimicrobial peptides (AMPs) are promising broad-spectrum antibiotic candidates in the wake of multi-drug resistant pathogens. Their clinical use still requires a solution based on lead optimisation and/or formulation to overcome certain limitations, such as unwanted cytotoxicity. A prodrug approach could overcome this safety barrier and can be achieved through reversible reduction or neutralisation of the AMPs' net cationic charge.

Observational cross-sectional study of nasal staphylococcal species of medical students of diverse geographical origin, prior to healthcare exposure: prevalence of SCC, , and the arginine catabolite mobile element (ACME) in the absence of selective antibiotic pressure.

Objective: The aim of this study was to investigate co-located nasal and coagulase-negative staphylococci (CoNS) (mainly ), recovered from healthy medical students in their preclinical year, prior to exposure to the healthcare environment, for the carriage of genes and genetic elements common to both species and that may contribute to and methicillin-resistant (MRSA) evolution.

Design: Prospective observational cross-sectional study. Carriage of antimicrobial resistance and virulence-associated genes in the absence of significant antibiotic selective pressure was investigated among healthy medical students from geographically diverse origins who were nasally co-colonised with and CoNS.

Vancomycin-Resistant Enterococci (VRE) in The Intensive Care Unit in a Nonoutbreak Setting: Identification of Potential Reservoirs and Epidemiological Associations Between Patient and Environmental VRE.

OBJECTIVE Among nosocomial bloodstream infections caused by enterococcal species, Ireland has the highest proportion caused by vancomycin-resistant enterococci (VRE) in Europe at 45.8%. The contribution of the near-patient environment to VRE transmission outside of outbreaks was investigated.

Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides.

Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S.

Using Disease-Associated Enzymes to Activate Antimicrobial Peptide Prodrugs.

Prodrugs of antimicrobial peptides can be generated by modifying their sequences at their N-termini with a linker and a negatively charged promoiety. These modifications can be selectively reversed by a disease-associated enzyme, thereby confining the activity of the peptide to pathologically affected body parts. A general method for the generation of prodrug candidates, based on a linker constituting the substrate of a disease-associated protease and an oligo-glutamic acid promoiety, as well as a protocol to validate the activation of the prodrug, are described herein.

The Molecular Epidemiology of Resistance in Cefotaximase-Producing Escherichia coli Clinical Isolates from Dublin, Ireland.

In view of continued high clinical prevalence of infections involving extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, this study sought to characterise the blaCTX-M genes, their associated mobile genetic elements and the integrons present in 100 ESBL-producing E. coli isolates collected in a Dublin hospital and associated community healthcare facilities. Polymerase chain reaction (PCR) mapping and sequencing was used to detect blaCTX-M alleles, their associated insertion sequences (ISs) and class 1 and 2 integrons in the collection.

A novel dual-functioning ruthenium(II)-arene complex of an anti-microbial ciprofloxacin derivative - Anti-proliferative and anti-microbial activity.

7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η(6)-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.

Differential In Vitro and In Vivo Toxicities of Antimicrobial Peptide Prodrugs for Potential Use in Cystic Fibrosis.

There has been considerable interest in the use of antimicrobial peptides (AMPs) as antimicrobial agents for the treatment of many conditions, including cystic fibrosis (CF). The challenging conditions of the CF patient lung require robust AMPs that are active in an environment of high proteolytic activity but that also have low cytotoxicity and immunogenicity. Previously, we developed prodrugs of AMPs that limited the cytotoxic effects of AMP treatment by rendering the antimicrobial activity dependent on the host enzyme neutrophil elastase (NE).

Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S.

Cytokine responses to Staphylococcus aureus bloodstream infection differ between patient cohorts that have different clinical courses of infection.

Background: The clinical course of Staphylococcus aureus bloodstream infection is unpredictable and bacterial virulence, host immune response and patient characteristics are among the factors that contribute to the clinical course of infection. To investigate the relationship between cytokine response and clinical outcome, circulating cytokine levels were investigated in response to S. aureus bloodstream infection in patients with different clinical courses of infection.