An effective antibiofilm strategy based on bacteriophages armed with silver nanoparticles.

The emerging antibiotic resistance in pathogenic bacteria is a key problem in modern medicine that has led to a search for novel therapeutic strategies. A potential approach for managing such bacteria involves the use of their natural killers, namely lytic bacteriophages. Another effective method involves the use of metal nanoparticles with antimicrobial properties. However, the use of lytic phages armed with nanoparticles as an effective antimicrobial strategy, particularly with respect to biofilms, remains unexplored. Here, we show that T7 phages armed with silver nanoparticles exhibit greater efficacy in terms of controlling bacterial biofilm, compared with phages or nanoparticles alone. We initially identified a novel silver nanoparticle-binding peptide, then constructed T7 phages that successfully displayed the peptide on the outer surface of the viral head. These recombinant, AgNP-binding phages could effectively eradicate bacterial biofilm, even when used at low concentrations. Additionally, when used at concentrations that could eradicate bacterial biofilm, T7 phages armed with silver nanoparticles were not toxic to eukaryotic cells. Our results show that the novel combination of lytic phages with phage-bound silver nanoparticles is an effective, synergistic and safe strategy for the treatment of bacterial biofilms.

Prospective, Long-Term Functional Outcomes of Extra-Osseous Talotarsal Stabilization (EOTTS) Using HyProCure in Adult Patients with Talotarsal Joint Instability: Assessment of Physical Activity and Patient Satisfaction.

BACKGROUND: The partial dislocation of the talus from the calcaneus and navicular bones is a primary factor leading to a prolonged overpronation during weightbearing. This study aimed to assess the possibility of returning to physical activity and long-term patient satisfaction after an extra-osseous talotarsal stabilization (EOTTS) procedure with a HyProCure sinus tarsi implant for partial talotarsal joint dislocation (TTJ). METHODS: A total of 41 adult patients (61 feet), with an average age of 46.41, were included and treated surgically with EOTTS as a stand-alone surgery. Physical activity and functional scores were assessed pre- and post-operatively using questionnaires-the UCLA Activity Score, Symptom-Related Ankle Activity Scale (SAAS), Sports Frequency Score (SFS), Lower Extremity Functional Scale (LEFS), and VAS scale. Satisfaction was assessed on a ten-point scale. The follow-up period was on average 8.61 years (from 7.33 to 10.31). RESULTS: EOTTS had a positive impact on physical activity, and a high rate of patient satisfaction (8.95 ± 1.9) was noted. The treatment led to a reduction in foot pain, as well as an increase in SAAS and LEFS scores (15,6% and 19,3%, respectively, p <0.01). The VAS pain score decreased by 18,6% (p <0.001). SFS and UCLA scores showed a small increase, but it was not statistically significant. A positive correlation was noted between patient satisfaction and time of physical activity per week (R = 0.33, p =0.04), and also between patient satisfaction and SAAS scores (R = 0.43, p =0.005). Pain from other joints (knee, hip) was eliminated or reduced in 40% of patients after surgery. CONCLUSIONS: EOTTS with a HyProCure implant is an effective long-term treatment option for partial talotarsal joint dislocation, leading to a reduction in foot pain and increased patient satisfaction, and allowing for a return to physical activity.

The Synthesis and Evaluation of Diethyl Benzylphosphonates as Potential Antimicrobial Agents.

The impact of substituent at phenyl ring of diethyl benzylphosphonate derivatives on cytotoxic activity was studied. The organophosphonates were obtained based on developed palladium-catalyzed α, ß-homodiarylation of vinyl esters protocol. The new synthetic pathway toward 1,2-bis(4-((diethoxyphosphoryl)methyl)phenyl)ethyl acetate was proposed which significantly improves the overall yield of the final product (from 1% to 38%). Several newly synthesized organophosphonates were tested as new potential antimicrobial drugs on model Escherichia coli bacterial strains (K12 and R2-R3). All tested compounds show the highest selectivity and activity against K12 and R2 strains. Preliminary cellular studies using MIC and MBC tests and digestion of Fpg after modification of bacterial DNA suggest that selected benzylphosphonate derivatives may have greater potential as antibacterial agents than typically used antibiotics such as ciprofloxacin, bleomycin and cloxacillin. These compounds are highly specific for pathogenic E. coli strains based on the model strains used and may be engaged in the future as new substitutes for commonly used antibiotics, which is especially important due to the increasing resistance of bacteria to various drugs and antibiotics.

Promiscuous Lipase-Catalyzed Knoevenagel-Phospha-Michael Reaction for the Synthesis of Antimicrobial ß-Phosphono Malonates.

An enzymatic route for phosphorous-carbon bond formation was developed by discovering new promiscuous activity of lipase. We reported a new metal-free biocatalytic method for the synthesis of pharmacologically relevant ß-phosphonomalononitriles via a lipase-catalyzed one-pot Knoevenagel-phospha-Michael reaction. We carefully analyzed the best conditions for the given reaction: the type of enzyme, temperature, and type of solvent. A series of target compounds was synthesized, with yields ranging from 43% to 93% by enzymatic reaction with Candida cylindracea (CcL) lipase as recyclable and, a few times, reusable catalyst. The advantages of this protocol are excellent yields, mild reaction conditions, low costs, and sustainability. The applicability of the same catalyst in the synthesis of ß-phosphononitriles is also described. Further, the obtained compounds were validated as new potential antimicrobial agents with characteristic E. coli bacterial strains. The pivotal role of such a group of phosphonate derivatives on inhibitory activity against selected pathogenic E. coli strains was revealed. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics. The impact of the ß-phosphono malonate chemical structure on antimicrobial activity was demonstrated. The crucial role of the substituents attached to the aromatic ring on the inhibitory action against selected pathogenic E. coli strains was revealed. Among tested compounds, four ß-phosphonate derivatives showed an antimicrobial activity profile similar to that obtained with currently used antibiotics such as ciprofloxacin, bleomycin, and cloxacillin. In addition, the obtained compounds constitute a convenient platform for further chemical functionalization, allowing for a convenient change in their biological activity profile. It should also be noted that the cost of the compounds obtained is low, which may be an attractive alternative to the currently used antimicrobial agents. The observed results are especially important because of the increasing resistance of bacteria to various drugs and antibiotics.

Relationship between Structure and Antibacterial Activity of α-Aminophosphonate Derivatives Obtained via Lipase-Catalyzed Kabachnik-Fields Reaction.

We reported a new method dealing with the synthesis of novel pharmacologically relevant α-aminophosphonate derivatives via a lipase-catalyzed Kabachnik−Fields reaction with yields of up to 93%. The advantages of this protocol are excellent yields, mild reaction conditions, low costs, and sustainability. The developed protocol is applicable to a range of H-phosphites and organic amines, providing a wide substrate scope. A new class of α-aminophosphonate analogues possessing P-chiral centers was also synthesized. The synthesized compounds were characterized on the basis of their antimicrobial activities against E. coli. The impact of the various alkoxy groups on antimicrobial activity was demonstrated. The crucial role of the substituents, located at the aromatic rings in the phenylethyloxy and benzyloxy groups, on the inhibitory action against selected pathogenic E. coli strains was revealed. The observed results are especially important because of increasing resistance of bacteria to various drugs and antibiotics.

Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in E. coli Strains.

An efficient method for the synthesis of functionalized peptidomimetics via multicomponent Ugi reaction has been developed. The application of trifluoroethanol (TFE) as a reaction medium provided desired products with good yields. Further, using the developed cyclisation reaction, the obtained peptidomimetics were transformed into the cyclic analogues (diketopiperazines, DKPs). The goal of the performed studies was to revised and compare whether the structure of the obtained structurally flexible acyclic peptidomimetics and their rigid cycling analogue DKPs affect antimicrobial activity. We studied the potential of synthesized peptidomimetics, both cyclic and acyclic, as antimicrobial drugs on model E. coli bacteria strains (k12, R2-R4). The biological assays reveal that DKPs hold more potential as antimicrobial drugs compared to open chain Ugi peptidomimetics. We believe that it can be due to the rigid cyclic structure of DKPs which promotes the membrane penetration in the cell of studied pathogens. The obtained data clearly indicate the high antibiotic potential of synthesized diketopiperazine derivatives over tested antibiotics.

The Synthesis and Evaluation of Amidoximes as Cytotoxic Agents on Model Bacterial E. coli Strains.

The biological research on newly synthesized amidoximes, Boc-protected amidoximes and Boc-derived amidines, obtained by a reduction of the parent amidoximes is reported, herein. Due to the presence of a free amino group in both amidines and amidoximes, these compounds can undergo various chemical reactions such as N-alkylation and N-acylation. One such reaction is Boc-protection, often used in organic synthesis to protect the amino and imino groups. Until now, Boc-protected amidoximes have not been tested for biological activity. Amidoxime derivatives were tested on bacterial E. coli strains. Initial cellular studies tests and digestion with Fpg after the modification of bacterial DNA, suggest that these compounds may have greater potential as antibacterial agents compared to antibiotics such as ciprofloxacin (ci), bleomycin (b) and cloxacillin (cl). The described compounds are highly specific for pathogenic E. coli strains on the basis of the model strains used and may be used in the future as new substitutes for commonly used antibiotics in clinical and hospital infections in the pandemic era.

The Synthesis and Evaluation of Aminocoumarin Peptidomimetics as Cytotoxic Agents on Model Bacterial E. coli Strains.

This work presents the successful synthesis of a library of novel peptidomimetics via Ugi multicomponent reaction. Most of these peptidomimetics contain differently substituted aminocoumarin; 7-amino-4-methylcoumarin and 7-amino-4-(trifluoromethyl) coumarin. Inspired by the biological properties of coumarin derivatives and peptidomimetics, we proposed the synthesis of coumarin incorporated peptidomimetics. We studied the potential of synthesized compounds as antimicrobial drugs on model E. coli bacterial strains (k12 and R2-R4). To highlight the importance of coumarin in antimicrobial resistance, we also synthesized the structurally similar peptidomimetics, using benzylamine. Preliminary cellular studies suggest that the compounds with coumarin derivatives have more potential as antimicrobial agents compared to the compounds without coumarin. We also analyzed the effect of aldehyde, free acid group and ester group on the course of their antimicrobial properties.

Pyridine Derivatives-A New Class of Compounds That Are Toxic to E. coli K12, R2-R4 Strains.

A preliminary study of 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines as new potential antimicrobial drugs was performed. Special emphasis was placed on the selection of the structure of target pyridine derivatives with the highest biological activity against different types of Gram-stained bacteria by lipopolysaccharide (LPS). Herein, Escherichia coli model strains K12 (without LPS in its structure) and R2-R4 (with different lengths of LPS in its structure) were used. Studied target compounds were provided with yields ranging from 53% to 91% by the lipase-catalyzed one pot multicomponent reaction of various aromatic aldehydes with malononitrile, and thiols. The presented work showed that the antibacterial activity of the studied pyridines depends on their structure and affects the LPS of bacteria. Moreover, the influence of the pyridines on bacteria possessing smooth and rough LPS and oxidative damage to plasmid DNA caused by investigated compounds was indicated. Additionally, the modification of the bacterial DNA with the tested compounds was performed to detect new potential oxidative damages, which are recognized by the Fpg protein. The obtained damage modification values of the analyzed compounds were compared with the modifications after antibiotics were used in this type of research. The presented studies demonstrate that 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines can be used as substitutes for known antibiotics. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.

Protective Action of L. salivarius SGL03 and Lactoferrin against COVID-19 Infections in Human Nasopharynx.

In this study, we used live viral particles from oral secretions from 17 people infected with SARS-CoV-2 and from 17 healthy volunteers, which were plated on a suitable medium complete for all microorganisms and minimal for L.salivarius growth. Both types of media also contained an appropriately prepared vector system pGEM-5Zf (+) based on the lactose operon (beta-galactosidase system). Incubation was carried out on both types of media for 24 h with the addition of 200 µL of Salistat SGL03 solution in order to test its inhibitory effect on the coronavirus contained in the oral mucosa and nasopharynx, visible as light blue virus particles on the test plates, which gradually disappeared in the material collected from infected persons over time. Regardless of the conducted experiments, swabs were additionally taken from the nasopharynx of infected and healthy people after rinsing the throat and oral mucosa with Salistat SGL03. In both types of experiments, after 24 h of incubation on appropriate media with biological material, we did not find any virus particles. Results were also confirmed by MIC and MBC tests. Results prove that lactoferrin, as one of the ingredients of the preparation, is probably a factor that blocks the attachment of virus particles to the host cells, determining its anti-viral properties. The conducted preliminary experiments constitute a very promising model for further research on the anti-viral properties of the ingredients contained in the Salistat SGL03 dietary supplement.

δ-Lactones-A New Class of Compounds That Are Toxic to E. coli K12 and R2-R4 Strains.

Lactones are among the well-known organic substances with a specific taste and smell. They are characterized by antibacterial, antiviral, anti-inflammatory, and anti-cancer properties. In recent years, among this group of compounds, new biologically active substances have been searched by modifying the main (leading) structure with new analogs with stronger or different responses that may have a toxic effect on the cells of pathogenic bacteria and constitute an alternative to commonly used antibiotics. A preliminary study of δ-lactone derivatives as new potential candidates for antibacterial drugs was conducted. Particular emphasis was placed on the selection of the structure of lactones with the highest biological activity, especially those with fluorine in their structure as a substituent in terms of action on bacterial lipopolysaccharide (LPS) in the model strains of Escherichia coli K12 (without LPS in its structure) and R2-R4 (LPS of different lengths in its structure). In the presented studies, on the basis of the conducted MIC and MBC tests, it was shown that the antibacterial (toxic) activity of lactones depends on their structure and the length of the bacterial LPS in the membrane of specific strains. Moreover, oxidative damage of bacterial DNA isolated from bacteria after modification with newly synthesized compounds after application of the repair enzyme Fpg glycosylase was analyzed. The analyzed damage values were compared with the modification with appropriate antibiotics: ciprofloxacin, bleomycin, and cloxacillin. The presented research clearly shows that lactone derivatives can be potential candidates as substitutes for drugs, e.g., the analyzed antibiotics. Their chemical and biological activity is related to coumarin derivatives and the corresponding δ-lactone groups in the structure of the substituent. The observed results are of particular importance in the case of increasing bacterial resistance to various drugs and antibiotics, especially in nosocomial infections and neoplasms, and in the era of a microbial pandemic.

1,2-Diarylethanols-A New Class of Compounds That Are Toxic to E. coli K12, R2-R4 Strains.

An initial study of 1,2-diarylethanols derivatives as new potential antibacterial drugs candidates was conducted. Particular emphasis was placed on the selection of the structure of 1,2-diarylethanols with the highest biological activity of lipopolysaccharides (LPS) in the model strains of Escherichia coli K12 (without LPS in its structure) and R2-R4 (with different lengths of LPS in its structure). In the presented studies, based on the conducted minimum inhibitory concentration (MIC) and MBC tests, it was demonstrated that the antibacterial (toxic) effect of 1,2-diarylethanols depends on their structure and the length of LPS bacteria in the membrane of specific strains. Moreover, the oxidative damage of bacterial DNA isolated from bacteria after modification with newly synthesized compounds after application of the repair enzyme Fpg glycosylases was analysed. The analysed damage values were compared with modification with appropriate antibiotics; bacterial DNA after the use of kanamycin, streptomycin, ciprofloxacin, bleomycin and cloxicillin. The presented research clearly shows that 1,2-diarylethanol derivatives can be used as potential candidates for substitutes for new drugs, e.g., the analysed antibiotics. Their chemical and biological activity is related to two aromatic groups and the corresponding chemical groups in the structure of the substituent. The observed results are particularly important in the case of increasing bacterial resistance to various drugs and antibiotics, especially in nosocomial infections and neoplasms, and in the era of pandemics caused by microorganisms.

All That Glitters Is Not Silver-A New Look at Microbiological and Medical Applications of Silver Nanoparticles.

Silver and its nanoparticles (AgNPs) have different faces, providing different applications. In recent years, the number of positive nanosilver applications has increased substantially. It has been proven that AgNPs inhibit the growth and survival of bacteria, including human and animal pathogens, as well as fungi, protozoa and arthropods. Silver nanoparticles are known from their antiviral and anti-cancer properties; however, they are also very popular in medical and pharmaceutical nanoengineering as carriers for precise delivery of therapeutic compounds, in the diagnostics of different diseases and in optics and chemistry, where they act as sensors, conductors and substrates for various syntheses. The activity of AgNPs has not been fully discovered; therefore, we need interdisciplinary research to fulfil this knowledge. New forms of products with silver will certainly find application in the future treatment of many complicated and difficult to treat diseases. There is still a lack of appropriate and precise legal condition regarding the circulation of nanomaterials and the rules governing their safety use. The relatively low toxicity, relative biocompatibility and selectivity of nanoparticle interaction combined with the unusual biological properties allow their use in animal production as well as in bioengineering and medicine. Despite a quite big knowledge on this topic, there is still a need to organize the data on AgNPs in relation to specific microorganisms such as bacteria, viruses or fungi. We decided to put this knowledge together and try to show positive and negative effects on prokaryotic and eukaryotic cells.

α-Amidoamids as New Replacements of Antibiotics-Research on the Chosen K12, R2-R4 E. coli Strains.

A preliminary study of α-amidoamids as new potential antimicrobial drugs was performed. Special emphasis was placed on selection of structure of α-amidoamids with the highest biological activity against different types of Gram-stained bacteria by lipopolysaccharide (LPS). Herein, Escherichia coli model strains K12 (without LPS in its structure) and R1-R4 (with different length LPS in its structure) were used. The presented work showed that the antibacterial activity of α-amidoamids depends on their structure and affects the LPS of bacteria. Moreover, the influence of various newly synthesized α-amidoamids on bacteria possessing smooth and rought LPS and oxidative damage of plasmid DNA caused by all newly obtained compounds was indicated. The presented studies clearly explain that α-amidoamids can be used as substitutes for antibiotics. The chemical and biological activity of the analysed α-amidoamids was associated with short alkyl chain and different isocyanides molecules in their structure such as: tetr-butyl isocyanide or 2,5-dimethoxybenzyl isocyanide. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.

Effect of Ligilactobacillus salivarius and Other Natural Components against Anaerobic Periodontal Bacteria.

In this present study, the bacteriostatic effect of Salistat SGL03 and the Lactobacillus salivarius strain contained in it was investigated in adults in in vivo and in vitro tests on selected red complex bacteria living in the subgingival plaque, inducing a disease called periodontitis, i.e., chronic periodontitis. Untreated periodontitis can lead to the destruction of the gums, root cementum, periodontium, and alveolar bone. Anaerobic bacteria, called periopathogens or periodontopathogens, play a key role in the etiopathogenesis of periodontitis. The most important periopathogens of the oral microbiota are: Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and others. Our hypothesis was verified by taking swabs of scrapings from the surface of the teeth of female hygienists (volunteers) on full and selective growth media for L. salivarius. The sizes of the zones of growth inhibition of periopathogens on the media were measured before (in vitro) and after consumption (in vivo) of Salistat SGL03, based on the disk diffusion method, which is one of the methods of testing antibiotic resistance and drug susceptibility of pathogenic microorganisms. Additionally, each of the periopathogens analyzed by the reduction inoculation method, was treated with L. salivarius contained in the SGL03 preparation and incubated together in Petri dishes. The bacteriostatic activity of SGL03 preparation in selected periopathogens was also analyzed using the minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests. The obtained results suggest the possibility of using the Salistat SGL03 dietary supplement in the prophylaxis and support of the treatment of periodontitis-already treated as a civilization disease.

Coumarin Derivatives as New Toxic Compounds to Selected K12, R1-R4 E. coli Strains.

Coumarins are natural compounds that were detected in 80 species of plants. They have numerous applications including the medical, food, tobacco, perfumery, and spirit industries. They show anti-swelling and diastolic effects. However, excess consumption of coumarins may adversely affect our health, because they are easily absorbed from the intestines into the lymph and blood, causing cirrhosis of the liver. Peptidomimetics are molecules whose structure and function are similar to those of peptides. They are an important group of compounds with biological, microbiological, anti-inflammatory, and anti-cancer properties. Therefore, studies on new peptidomimetics, which load the effect of native peptides, whose half-life in the body is much longer due to structural modifications, are extremely important. A preliminary study of coumarin analogues and its derivatives as new potential antimicrobial drugs containing carboxylic acid or ester was performed to determine their basic structure related to their biological features against various types of Gram-stained bacteria by lipopolysaccharide (LPS). We hypothesized that the toxicity (antibacterial activity) of coumarin derivatives is dependent on the of LPS in bacteria and nature and position of the substituent which may be carboxylic acid, hydroxyl groups, or esters. In order to verify this hypothesis, we used K12 (smooth) and R1-R4 (rough) Escherichia coli strains which are characterized by differences in the type of LPS, especially in the O-antigen region, the outermost LPS layer. In our work, we synthesized 17 peptidomimetics containing a coumarin scaffold and checked their influence on K12 and R1-R4 E. coli strains possessing smooth and rough LPS. We also measured the damage of plasmid DNA caused by target compounds. The results of our studies clearly support the conclusion that coumarin peptidomimetics are antagonistic compounds to many of the currently used antibiotics. The high biological activity of the selected coumarin peptidomimetic was associated with identification of the so-called magic methyl groups, which substantially change the biochemical properties of target compounds. Investigating the effects of these compounds is particularly important in the era of increasingly common resistance in bacteria.

Identification and Characterization of the First Virulent Phages, Including a Novel Jumbo Virus, Infecting Ochrobactrum spp.

The Ochrobactrum genus consists of an extensive repertoire of biotechnologically valuable bacterial strains but also opportunistic pathogens. In our previous study, a novel strain, Ochrobactrum sp. POC9, which enhances biogas production in wastewater treatment plants (WWTPs) was identified and thoroughly characterized. Despite an insightful analysis of that bacterium, its susceptibility to bacteriophages present in WWTPs has not been evaluated. Using raw sewage sample from WWTP and applying the enrichment method, two virulent phages, vB_OspM_OC and vB_OspP_OH, which infect the POC9 strain, were isolated. These are the first virulent phages infecting Ochrobactrum spp. identified so far. Both phages were subjected to thorough functional and genomic analyses, which allowed classification of the vB_OspM_OC virus as a novel jumbo phage, with a genome size of over 227 kb. This phage encodes DNA methyltransferase, which mimics the specificity of cell cycle regulated CcrM methylase, a component of the epigenetic regulatory circuits in Alphaproteobacteria. In this study, an analysis of the overall diversity of Ochrobactrum-specific (pro)phages retrieved from databases and extracted in silico from bacterial genomes was also performed. Complex genome mining allowed us to build similarity networks to compare 281 Ochrobactrum-specific viruses. Analyses of the obtained networks revealed a high diversity of Ochrobactrum phages and their dissimilarity to the viruses infecting other bacteria.

Characterization of a Unique Bordetella bronchiseptica vB_BbrP_BB8 Bacteriophage and Its Application as an Antibacterial Agent.

Bordetella bronchiseptica, an emerging zoonotic pathogen, infects a broad range of mammalian hosts. B. bronchiseptica-associated atrophic rhinitis incurs substantial losses to the pig breeding industry. The true burden of human disease caused by B. bronchiseptica is unknown, but it has been postulated that some hypervirulent B. bronchiseptica isolates may be responsible for undiagnosed respiratory infections in humans. B. bronchiseptica was shown to acquire antibiotic resistance genes from other bacterial genera, especially Escherichia coli. Here, we present a new B. bronchiseptica lytic bacteriophage-vB_BbrP_BB8-of the Podoviridae family, which offers a safe alternative to antibiotic treatment of B. bronchiseptica infections. We explored the phage at the level of genome, physiology, morphology, and infection kinetics. Its therapeutic potential was investigated in biofilms and in an in vivo Galleria mellonella model, both of which mimic the natural environment of infection. The BB8 is a unique phage with a genome structure resembling that of T7-like phages. Its latent period is 75 ± 5 min and its burst size is 88 ± 10 phages. The BB8 infection causes complete lysis of B. bronchiseptica cultures irrespective of the MOI used. The phage efficiently removes bacterial biofilm and prevents the lethality induced by B. bronchiseptica in G. mellonella honeycomb moth larvae.

The Use of Liquids Ionic Fluids as Pharmaceutically Active Substances Helpful in Combating Nosocomial Infections Induced by Klebsiella Pneumoniae New Delhi Strain, Acinetobacter Baumannii and Enterococcus Species.

This review deals with various microbiological activities of ionic liquids, which constitute the first anti-infective defense against multi-drug-resistant bacteria-with a particular emphasis placed on medicine and pharmacology. The quoted data on the biological activity of ionic liquids including their antimicrobial properties (depending on the type of a cation or an anion) and are discussed in view of possible applications in nosocomial infections. Dedicated attention is given to finding infections with the Klebsiella pneumoniae New Delhi strain, Acinetobacter baumannii, and Enterococcus species, which are responsible for the induction of antibiotic resistance in intensive care units. Diagnosis and treatment using current antibiotics is a significant problem in hospital care, and the relevant burden on the health systems of the European Union member states induces the search for new, effective methods of treatment. Ionic liquids, due to their antibacterial effect, can be considered topical and general medications and may provide the basis for treatment to eliminate the antibiotic resistance phenomenon in the future. At present, the number of infections with resistant pathogens in hospitals and outpatient clinics in the European Union is growing. In 2015⁻2017, a significant incidence of respiratory and bloodstream infections with bacteria resistant to antibiotics from the 3rd generation group of cephalosporins, glycopeptides, and carbapenems were observed. The paper presents examples of synthesized bifunctional salts with at least one pharmaceutically active ion in obtaining a controlled release, controlled delivery, and biological impact on the pathogenic bacteria, viruses and fungi. The ionic liquids obtained in the presented way may find applications in the treatment of wounds and infections.

Biological reconstruction of large osteochondral lesions of the talar dome with a modified "sandwich" technique-Midterm results.

BACKGROUND: Surgical treatment for large osteochondral lesions of the talar dome (OLTD) must restore the convexity and curvature of the talus. Here, we present midterm results and describe the modified "sandwich" reconstruction procedure. Bone defects were restored using a biological inlay consists of autologous bone chips that were mixed with bone marrow concentrate and fibrin glue and covered with a xenogeneic collagen membrane infiltrated with bone marrow concentrate and stabilized by fibrin glue. METHODS: Ten patients who were treated using a modified "sandwich" OLTD reconstruction were assessed after an average follow-up period of 46.4 (±18) months, using the clinical American Orthopaedic Foot and Ankle Society Ankle Hindfoot Scale (AOFAS) score and radiological magnetic resonance observation of cartilage repair tissue (MOCART) score. RESULTS: The mean AOFAS score increased significantly from 58.3 (±8.5) points to 81.8 (±15.5) points as well the mean VAS score reduced significantly from 5.58 (±0.97) to 1.83 (±0.93) points. The average MOCART score was 69.5% (±16.7%) in the final follow-up. CONCLUSIONS: The presented modified "sandwich" technique permanently recreates the convexity and curvature in large osteochondral lesions of the talar dome with a single step surgical procedure.