Silicone Rubber and Microcrystalline Cellulose Composites with Antimicrobial Properties

The goal of this study was to create polydimethylsiloxane (PDMS) and microcrystalline cellulose (MCC) composites with high mechanical properties and antimicrobial activity. Vinyl-terminated PDMS was mixed with bifunctional filler, which combines MCC stiffness and antimicrobial properties of silver nanoparticles. To provide antimicrobial properties the silver nanoparticles in situ were synthesized by chemical reducing method in MCC aqueous suspension. Silver nanoparticles (AgNPs) concentration deposited on MCC particles surface was varied. The morphology, antimicrobial activity and mechanical properties of PDMS/MCC composites and their components have been investigated. It was shown that the combination of MCC/AgNPs as a filler and PDMS as matrix advantages bring multifunctional properties to polymer matrix composite. DOI: http://dx.doi.org/10.5755/j01.ms.20.1.4397</p

Discovery and development of safe-in-man broad-spectrum antiviral agents

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of the general population from emerging and re-emerging viral diseases, reinforcing the arsenal of available antiviral options. Here, we review discovery and development of BSAAs and summarize the information on 120 safe-in-man agents in a freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand the spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.Non peer reviewe

Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections

Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFNα, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFNα–remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFNα combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies. Conclusions: Altogether, our results indicated that IFNα can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections

Emergence and spread of SARS-CoV-2 lineage B.1.620 with variant of concern-like mutations and deletions.

Distinct SARS-CoV-2 lineages, discovered through various genomic surveillance initiatives, have emerged during the pandemic following unprecedented reductions in worldwide human mobility. We here describe a SARS-CoV-2 lineage - designated B.1.620 - discovered in Lithuania and carrying many mutations and deletions in the spike protein shared with widespread variants of concern (VOCs), including E484K, S477N and deletions HV69Δ, Y144Δ, and LLA241/243Δ. As well as documenting the suite of mutations this lineage carries, we also describe its potential to be resistant to neutralising antibodies, accompanying travel histories for a subset of European cases, evidence of local B.1.620 transmission in Europe with a focus on Lithuania, and significance of its prevalence in Central Africa owing to recent genome sequencing efforts there. We make a case for its likely Central African origin using advanced phylogeographic inference methodologies incorporating recorded travel histories of infected travellers

Pseudomonas aeruginosa bacteremia: resistance to antibiotics, risk factors, and patient mortality

The aim of our study was to determine the prevalence of Pseudomonas aeruginosa bacteremia, risk factors, and outcome of patients treated at the Hospital of Kaunas University of Medicine. Material and methods. All hospitalized patients with blood culture positive for Pseudomonas aeruginosa during the 5-year period were included. A retrospective data analysis was performed to evaluate patients’ risk factors and mortality caused by P. aeruginosa bacteremia. Results. A total of 47 (58.8%) bacteremia episodes occurred in an intensive care unit (ICU). A primary source of bacteremia was identified in 50 (62.5%) episodes. Overall mortality rate was 58.8%. Univariate risk factors analysis showed the factors, which significantly increased the risk of death: mechanical ventilation (13.67 times, P&lt;0.001), patient hospitalization in the ICU (8.51 times, P&lt;0.001), acute respiratory failure (8.44 times, P&lt;0.001), infection site in the respiratory tract (4.93 times, P=0.003), and central vein catheter (4.44 times, P=0.002). Timely and appropriate treatment and surgery were significant protective factors for 30-day mortality (11.1 and 5.26 times, respectively; P=0.001). Meropenem-resistant Pseudomonas aeruginosa strains caused bacteremia more frequently in patients older than 65 years than meropenem-sensitive strains (57.9%, n=11). All 19 patients with meropenem-resistant Pseudomonas aeruginosa bacteremia received inappropriate empirical antibiotic therapy. Conclusions. Treatment at the intensive care unit, mechanical ventilation, acute respiratory failure, source of infection in respiratory tract, and central vein catheter are the major risk factors associated with an increased mortality rate in patients with Pseudomonas aeruginosa bacteremia. The patients older than 65 years are at increased risk for bacteremia caused by carbapenemresistant Pseudomonas aeruginosa strains. Carbapenems are not antibiotics of the choice of treatment for Pseudomonas aeruginosa bacteremia at the Hospital of Kaunas University of Medicine

Pathogenicity factors of potential hospital-acquired pneumonia pathogens, Pseudomonas aeruginosa and Klebsiella pneumoniae, and their influence on the course of disease

The aim of the study: To examine pathogenicity factors of Pseudomonas aeruginosa and Klebsiella pneumoniae strains, colonizing lower respiratory tract or causing hospital-acquired pneumonia, and to evaluate their influence on the course of hospital-acquired pneumonia. Objectives of the sudy: 1. To examine pathogenicity factors – resistance to serum bactericidal activity, ability to penetrate epithelial cells of the respiratory tract, dependence of O serogroup, and resistance to antibiotics – of Pseudomonas aeruginosa strains, colonizing lower respiratory tract or causing hospital-acquired pneumonia. 2. To evaluate the relationship between pathogenicity factors of Pseudomonas aeruginosa strains. 3. To examine the ability of Klebsiella pneumoniae strains, colonizing lower respiratory tract or causing hospital-acquired pneumonia, to produce extended-spectrum beta-lactamases and resistance of these pathogen to antibiotics. 4. To evaluate the influence of pathogenicity factors of Pseudomonas aeruginosa and Klebsiella pneumoniae strains on the course of hospital-acquired pneumonia. Such work is first in Lithuania, because we determined not only pathogenicity factors of Pseudomonas aeruginosa – i.e., resistance to bactericidal activity of serum, but also evaluated possible influence of Pseudomonas aeruginosa strains, having this pathogenicity factor, on hospital-acquired pneumonia development and outcome. Therefore, the ability of Pseudomonas aeruginosa strains to invasive into epithelial cells of respiratory tract and possible influence on hospital-acquired pneumonia course is being evaluated for the first time generally. In this work the ability of Klebsiella pneumoniae strains, colonizing lower respiratory tract or causing hospital-acquired pneumonia, to produce extended-spectrum beta-lactamases and resistance of these pathogen to antibiotics was compared

Associations between <i>β</i>-Lactamase Types of <i>Acinetobacter baumannii</i> and Antimicrobial Resistance

Background and objective: Acinetobacter baumannii (A. baumannii) is an important nosocomial pathogen that not only possesses intrinsic resistance to many classes of antibiotics, but is also capable of rapidly developing antimicrobial resistance during treatment. The aim of this study was to determine the characteristics of resistance of A. baumannii strains to β-lactams and other tested antibiotics, to evaluate the associations between the phenotypes of resistance to β-lactams and other tested antibiotics, and to evaluate the changes in antibiotic resistance of A. baumannii strains over 5 years by comparing the periods of 2016–2017 and 2020–2021. Materials and methods: A total of 233 A. baumannii strains were isolated from different clinical specimens of patients treated at the Hospital of Lithuanian University of Health Sciences in 2016–2017 (n = 130) and 2021–2022 (n = 103). All clinical cultures positive for A. baumannii were analyzed. The type of β-lactamase was detected by phenotypic methods using ESBL plus AmpC screen disk tests and the combination meropenem disk test. Results: In both periods, all A. baumannii strains were resistant to ciprofloxacin; resistance to carbapenems, piperacillin/tazobactam, gentamicin, and tobramycin was noted in more than 80% of strains. A comparison of two periods showed that the percentages of A. baumannii strains producing two or three types of β-lactamases were significantly greater in 2021–2022 than in 2016–2017 (94.2% and 5.8% vs. 17.7% and 2.3%, respectively, p β-lactamases were more often resistant to tigecycline, tetracycline, and doxycycline than strains producing one type of β-lactamase (p Conclusions: The frequency of isolation of A. baumannii strains producing two different types of β-lactamases (AmpC plus KPC, AmpC plus ESBL, or ESBL plus KPC) or three types of β-lactamases (AmpC, KPC, and ESBL) and the resistance rates to ampicillin/sulbactam, tigecycline, tetracycline, and doxycycline were significantly greater in 2020–2021 as compared with 2016–2017. The production of two or three types of β-lactamases by A. baumannii strains was associated with higher resistance rates to tetracyclines

Antibiotic Resistance Mechanisms of Clinically Important Bacteria

Bacterial resistance to antimicrobial drugs is an increasing health and economic problem. Bacteria may be innate resistant or acquire resistance to one or few classes of antimicrobial agents. Acquired resistance arises from: (i) mutations in cell genes (chromosomal mutation) leading to cross-resistance, (ii) gene transfer from one microorganism to other by plasmids (conjugation or transformation), transposons (conjugation), integrons and bacteriophages (transduction). After a bacterium gains resistance genes to protect itself from various antimicrobial agents, bacteria can use several biochemical types of resistance mechanisms: antibiotic inactivation (interference with cell wall synthesis, e.g., β-lactams and glycopeptide), target modification (inhibition of protein synthesis, e.g., macrolides and tetracyclines; interference with nucleic acid synthesis, e.g., fluoroquinolones and rifampin), altered permeability (changes in outer membrane, e.g., aminoglycosides; new membrane transporters, e.g., chloramphenicol), and “bypass” metabolic pathway (inhibition of metabolic pathway, e.g., trimethoprim-sulfamethoxazole)

Microbiological and biochemical characteristics of inflammatory tissues in the periodontium

Objective. To investigate bacterial populations in subgingival and supragingival plaque samples of patients with inflammatory periodontal diseases and activities of the lysosomal enzymes – lysozyme, alkaline phosphatase, and b-glucuronidase – in peripheral venous blood, in gingival crevicular fluid, and mixed nonstimulated saliva. Methods and materials. The study included 60 patients with inflammatory periodontal diseases without any internal pathology and 24 periodontally healthy subjects. Molecular genetic assay (Micro-IDent plus, Germany) for complex identification of additional six periodontopathic bacteria was applied. The activity of lysozyme was determined turbidimetrically, the activity of alkaline phosphatase – spectrophotometrically with a “Monarch” biochemical analyzer, the activity b-glucuronidase – according to the method described by Mead et al. and modified by Strachunskii. Results. A statistically significant association between clinical and bacteriological data was found in the following cases: gingival bleeding in the presence of Eubacterium nodatum, Eikenella corrodens, Capnocytophaga spp. (P&lt;0.01); pathological periodontal pockets in the presence of Peptostreptococcus micros (α≤0.05 and β≤0.2), Fusobacterium nucleatum (α≤0.05 and β≤0.2), Campylobacter rectus (α≤0.05 and β≤0.2), and Capnocytophaga spp. (P&lt;0.05); and satisfactory oral hygiene in the presence of all microorganisms investigated (P&lt;0.05). The activity of lysozyme in gingival crevicular fluid and mixed nonstimulated saliva indicates the severity of periodontal inflammation. Based on clinical data, in assessing the amount of lysozyme in mixed nonstimulated saliva, sensitivity and specificity of 100% was found. Increased activities of lysozyme, alkaline phosphatase, and b-glucuronidase were found in peripheral venous blood of patients with inflammatory periodontal disease as compared to control group. Conclusions. The main principles of the treatment of periodontal inflammatory diseases should be based on microorganism elimination, creation of individual treatment means affecting microflora in the mouth and immune system of macroorganisms

Relationship between isolation of extended spectrum beta-lactamase-producing Klebsiella pneumoniae and course of hospital-acquired pneumonia

Aim of the study. To evaluate relationship between isolation of extended spectrum beta-lactamaseproducing Klebsiella pneumoniae strains and course of hospital-acquired pneumonia. Materials and methods. K. pneumoniae strains isolated from bronchial secretions or bronchoalveolar lavage fluid samples of patients hospitalized at an intensive care unit of Kaunas University of Medicine Hospital were analyzed. By means of synergistic two-antibiotics disc method, K. pneumoniae strains producing extended spectrum beta-lactamases were selected for further analysis using E-test (AB Biodisk, Solna, Sweden). Hospitalacquired pneumonia was diagnosed based on standard criteria for the diagnosis of pneumonia if signs of pneumonia occurred after 48 hours following admission. Late-onset hospital-acquired pneumonia was considered if these signs of pneumonia occurred on fifth day of hospitalization or later. Results. Total of 45 strains of K. pneumoniae were isolated during the study period; 18 isolated strains produced ESBL. Thirty-two patients investigated have developed hospital-acquired pneumonia, 20 of which were cases of late-onset hospital-acquired pneumonia. Thirteen cases of K. pneumoniae isolation were classified as airway colonization. Extended spectrum beta-lactamase-producing K. pneumoniae strains were more frequently isolated from patients with hospital-acquired pneumonia (88.9%, n=16 and 11.1%, n=2, P&lt;0.05) in comparison with non-producing strains. Extended spectrum beta-lactamase-producing strains were more prevalent in late-onset pneumonia group (93.8%, n=15) than in early-onset group (6.2%, n=1, P&lt;0.001). Conclusions. Extended spectrum beta-lactamase-producing K. pneumoniae strains were more frequently isolated from patients with hospital-acquired pneumonia as compared to colonized patients. Extended spectrum beta-lactamase-producing K. pneumoniae strains were more frequently isolated from patients with late-onset hospital-acquired pneumonia