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Antibiotics, Volume 9, Issue 5 (May 2020) – 69 articles

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Open AccessArticle
Antimicrobial and Antifungal Activities of Terpene-Derived Palladium Complexes
Antibiotics 2020, 9(5), 277; https://doi.org/10.3390/antibiotics9050277 - 25 May 2020
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Abstract
In an era of multidrug-resistant bacterial infections overshadowed by a lack of innovation in the antimicrobial drug development pipeline, there has been a resurgence in multidisciplinary approaches aimed at tackling this global health problem. One such approach is to use metal complexes as [...] Read more.
In an era of multidrug-resistant bacterial infections overshadowed by a lack of innovation in the antimicrobial drug development pipeline, there has been a resurgence in multidisciplinary approaches aimed at tackling this global health problem. One such approach is to use metal complexes as a framework for new antimicrobials. Indeed, in this context, bismuth-, silver- and gold-derived compounds in particular have displayed demonstrable antimicrobial activity. In this work, we discuss the antimicrobial and antifungal activities of terpene-derived chiral palladium complexes against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Candida albicans, and Cryptococcus neoformans. It was established that all studied coordination compounds of palladium were highly active antifungal drugs. In contrast, the subset of palladacycles possessing a palladium–carbon bond were only active against the Gram-positive bacterium Staphylococcus aureus. All compounds were inactive against the Gram-negative bacteria tested. Full article
(This article belongs to the Special Issue Nontraditional Antibiotics—Challenges and Triumphs)
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Open AccessArticle
Isoniazid Conjugated Magnetic Nanoparticles Loaded with Amphotericin B as a Potent Antiamoebic Agent against Acanthamoeba castellanii
Antibiotics 2020, 9(5), 276; https://doi.org/10.3390/antibiotics9050276 - 25 May 2020
Viewed by 538
Abstract
The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, granulomatous amoebic encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these [...] Read more.
The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, granulomatous amoebic encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these infections; however, the host cell cytotoxicity of these drugs remains a challenge. Furthermore, Acanthamoeba species are capable of transforming to the cyst form to resist chemotherapy. Herein, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with isoniazid, which were further loaded with amphotericin B (ISO-NPs-AMP) to cause potent antiamoebic effects against Acanthamoeba castellanii. The IC50 of isoniazid conjugated with magnetic nanoparticles and loaded with amphotericin B was found to be 45 μg/mL against Acanthamoeba castellanii trophozoites and 50 μg/mL against cysts. The results obtained in this study have promising implications in drug discovery as these nanomaterials exhibited high trophicidal and cysticidal effects, as well as limited cytotoxicity against rat and human cells. Full article
(This article belongs to the Special Issue Antibiotic Conjugates: Applications from Tools to Drug Development)
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Open AccessArticle
Effect of Borrelia burgdorferi Outer Membrane Vesicles on Host Oxidative Stress Response
Antibiotics 2020, 9(5), 275; https://doi.org/10.3390/antibiotics9050275 - 25 May 2020
Viewed by 611
Abstract
Outer membrane vesicles (OMVs) are spherical bodies containing proteins and nucleic acids that are released by Gram-negative bacteria, including Borrelia burgdorferi, the causative agent of Lyme disease. The functional relationship between B. burgdorferi OMVs and host neuron homeostasis is not well understood. [...] Read more.
Outer membrane vesicles (OMVs) are spherical bodies containing proteins and nucleic acids that are released by Gram-negative bacteria, including Borrelia burgdorferi, the causative agent of Lyme disease. The functional relationship between B. burgdorferi OMVs and host neuron homeostasis is not well understood. The objective of this study was to examine how B. burgdorferi OMVs impact the host cell environment. First, an in vitro model was established by co-culturing human BE2C neuroblastoma cells with B. burgdorferi B31. B. burgdorferi was able to invade BE2C cells within 24 h. Despite internalization, BE2C cell viability and levels of apoptosis remained unchanged, but resulted in dramatically increased production of MCP-1 and MCP-2 cytokines. Elevated secretion of MCP-1 has previously been associated with changes in oxidative stress. BE2C cell mitochondrial superoxides were reduced as early as 30 min after exposure to B. burgdorferi and OMVs. To rule out whether BE2C cell antioxidant response is the cause of decline in superoxides, superoxide dismutase 2 (SOD2) gene expression was assessed. SOD2 expression was reduced upon exposure to B. burgdorferi, suggesting that B. burgdorferi might be responsible for superoxide reduction. These results suggest that B. burgdorferi modulates cell antioxidant defense and immune system reaction in response to the bacterial infection. In summary, these results show that B. burgdorferi OMVs serve to directly counter superoxide production in BE2C neurons, thereby ‘priming’ the host environment to support B. burgdorferi colonization. Full article
(This article belongs to the Special Issue Pathogen–Host Interaction by Borrelia burgdorferi)
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Open AccessArticle
In Vitro Antibacterial and Anti-Inflammatory Effects of Novel Insect Fungus Polycephalomyces phaothaiensis Extract and Its Constituents against Propionibacterium acnes
Antibiotics 2020, 9(5), 274; https://doi.org/10.3390/antibiotics9050274 - 25 May 2020
Viewed by 579
Abstract
Propionibacterium acnes plays an important role in the pathophysiology of acne vulgaris, the most common chronic inflammatory skin disease of the pilosebaceous unit. This study was conducted to investigate whether the entomopathogenic fungus Polycephalomyces phaothaiensis components have antibacterial and anti-inflammatory effects against P. [...] Read more.
Propionibacterium acnes plays an important role in the pathophysiology of acne vulgaris, the most common chronic inflammatory skin disease of the pilosebaceous unit. This study was conducted to investigate whether the entomopathogenic fungus Polycephalomyces phaothaiensis components have antibacterial and anti-inflammatory effects against P. acnes that may serve for acne treatment. A chemical study by spectroscopic analysis resulted in the identification of seven known compounds. The anti-P. acnes potency of extracts and test compounds was determined by both agar diffusion and broth dilution methods. The ethyl acetate extract from culture broth along with cordytropolone (1) and stipitalide (2) exhibited strong anti- P. acnes activity while (+)-piliformic acid (3) showed weak inhibitory activity. The anti-inflammatory effect of ethyl acetate extract and 13 was then examined by the quantification of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α on heat-killed P. acnes induced cytokine production by THP-1 cells. The result demonstrated that the extract and its constituents (13) showed a potent significant effect by inhibiting the P. acnes-induced pro-inflammatory cytokines production in THP-1. Our results suggest for the first time that P. phaothaiensis and its constituents (1 and 2) hold therapeutic value for further studies as a new alternative treatment for acne. Full article
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Open AccessArticle
Antibiotic Consumption on Dairy and Beef Cattle Farms of Central Italy Based on Paper Registers
Antibiotics 2020, 9(5), 273; https://doi.org/10.3390/antibiotics9050273 - 25 May 2020
Viewed by 565
Abstract
The overuse of antibiotics in livestock contributes to the antibiotic resistance pandemic. The assessment of the actual antibiotic consumption is crucial in limiting the expansion of the problem effectively. The aim of this study was to provide the first qualitative and quantitative analysis [...] Read more.
The overuse of antibiotics in livestock contributes to the antibiotic resistance pandemic. The assessment of the actual antibiotic consumption is crucial in limiting the expansion of the problem effectively. The aim of this study was to provide the first qualitative and quantitative analysis of antimicrobial usage using data from paper-based registers on dairy and beef farms located in the Umbria region, Italy. Antimicrobial therapies of a one-year period were collected from 101 farms with at least 50 cattle each. Defined daily doses (DDDvet) and defined course doses (DCDvet) were calculated per administration route and antimicrobial class. The total courses administered were fewer in beef (330.7 × 10−3 DCDvet/year) than in dairy farms (1034.1 × 10−3 DCDvet/year). The use of the highest priority critically important antimicrobials (HPCIAs) was higher (p = 0.0033) in dairy than in beef herds. In terms of DDDvet, the parenteral fluoroquinolone administration ranked second and fourth on dairy and beef farms, respectively; the consumption of beta-lactams was ten times higher on dairy than on beef farms. Our results confirm that intensive dairy management practices are associated with increased antibiotic consumption and highlight the necessity to strengthen the existing stewardship programs by involving all stakeholders in effective antimicrobial resistance reduction plans. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessArticle
In Vitro Activity of Essential Oils Against Planktonic and Biofilm Cells of Extended-Spectrum β-Lactamase (ESBL)/Carbapenamase-Producing Gram-Negative Bacteria Involved in Human Nosocomial Infections
Antibiotics 2020, 9(5), 272; https://doi.org/10.3390/antibiotics9050272 - 25 May 2020
Viewed by 738
Abstract
The aim of this study was to analyze the antibacterial activity of four essential oils (EOs), Melaleuca alternifolia, Eucalyptus globulus, Mentha piperita, and Thymus vulgaris, in preventing the development and spread of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, [...] Read more.
The aim of this study was to analyze the antibacterial activity of four essential oils (EOs), Melaleuca alternifolia, Eucalyptus globulus, Mentha piperita, and Thymus vulgaris, in preventing the development and spread of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, metallo-beta-lactamase (MBL)-producing Pseudomonas aeruginosa and carbapenemase (KPC)-producing Klebsiella pneumoniae. A total of 60 strains were obtained from the stock collection from the Microbiology Laboratory of Hesperia Hospital, Modena, Italy. Twenty ESBL-producing E. coli, 5 K. pneumoniae, 13 KPC-producing K. pneumoniae, and 20 MBL-producing P. aeruginosa were cultured and reconfirmed as ESBL and carbapenamase producers. Polymerase chain reaction was used for the detection of genes responsible for antibiotic resistance (ESBL and KPC/MBL). Antibacterial activity of the EOs was determined using the agar disk diffusion assay, and minimal inhibitory concentrations (MICs) were also evaluated. Lastly, adhesion capability and biofilm formation on polystyrene and glass surfaces were studied in 24 randomly selected strains. M. alternifolia and T. vulgaris EOs showed the best antibacterial activity against all tested strains and, as revealed by agar disk diffusion assay, M. alternifolia was the most effective, even at low concentrations. This effect was also confirmed by MICs, with values ranging from 0.5 to 16 µg/mL and from 1 to 16 µg/mL, for M. alternifolia and T. vulgaris EOs, respectively. The EOs’ antibacterial activity compared to antibiotics confirmed M. alternifolia EO as the best antibacterial agent. T. vulgaris EO also showed a good antibacterial activity with MICs lower than both reference antibiotics. Lastly, a significant anti-biofilm activity was observed for the two EOs (*P < 0.05 and **P < 0.01 for M. alternifolia and T. vulgaris EOs, respectively). A good antibacterial and anti-biofilm activity of M. alternifolia and T. vulgaris EOs against all selected strains was observed, thus demonstrating a future possible use of these EOs to treat infections caused by ESBL/carbapenemase-producing strains, even in association with antibiotics. Full article
(This article belongs to the Special Issue The Antimicrobial or Antitumor Activities of Essential Oils)
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Open AccessArticle
Mining the Biosynthetic Potential for Specialized Metabolism of a Streptomyces Soil Community
Antibiotics 2020, 9(5), 271; https://doi.org/10.3390/antibiotics9050271 - 23 May 2020
Viewed by 746
Abstract
The diversity and distribution of specialized metabolite gene clusters within a community of bacteria living in the same soil habitat are poorly documented. Here we analyzed the genomes of 8 Streptomyces isolated at micro-scale from a forest soil that belong to the same [...] Read more.
The diversity and distribution of specialized metabolite gene clusters within a community of bacteria living in the same soil habitat are poorly documented. Here we analyzed the genomes of 8 Streptomyces isolated at micro-scale from a forest soil that belong to the same species or to different species. The results reveal high levels of diversity, with a total of 261 biosynthesis gene clusters (BGCs) encoding metabolites such as terpenes, polyketides (PKs), non-ribosomal peptides (NRPs) and ribosomally synthesized and post-translationally modified peptides (RiPPs) with potential bioactivities. A significant part of these BGCs (n = 53) were unique to only one strain when only 5 were common to all strains. The metabolites belong to very diverse chemical families and revealed that a large diversity of metabolites can potentially be produced in the community. Although that analysis of the global metabolome using GC-MS revealed that most of the metabolites were shared between the strains, they exhibited a specific metabolic pattern. We also observed that the presence of these accessory pathways might result from frequent loss and gain of genes (horizontal transfer), showing that the potential of metabolite production is a dynamic phenomenon in the community. Sampling Streptomyces at the community level constitutes a good frame to discover new biosynthetic pathways and it appears as a promising reservoir for the discovery of new bioactive compounds. Full article
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Open AccessArticle
Isolation, Characterization and Chemical Synthesis of Large Spectrum Antimicrobial Cyclic Dipeptide (l-leu-l-pro) from Streptomyces misionensis V16R3Y1 Bacteria Extracts. A Novel 1H NMR Metabolomic Approach
Antibiotics 2020, 9(5), 270; https://doi.org/10.3390/antibiotics9050270 - 21 May 2020
Viewed by 708
Abstract
Streptomyces is the most frequently described genus of Actinomycetes, a producer of biologically active secondary metabolites. Indeed, the Streptomyces species produces about 70% of antibiotics and 60% of antifungal molecules used in agriculture. Our study was carried out with the goal of [...] Read more.
Streptomyces is the most frequently described genus of Actinomycetes, a producer of biologically active secondary metabolites. Indeed, the Streptomyces species produces about 70% of antibiotics and 60% of antifungal molecules used in agriculture. Our study was carried out with the goal of isolating and identifying antimicrobial secondary metabolites from Streptomyces misionensis V16R3Y1 isolated from the date palm rhizosphere (southern Tunisia). This strain presented a broad range of antifungal activity against Fusarium oxysporum, Aspergillus flavus, Penicillium expansum, Aspergillus niger, Candida albicans, Candida metapsilosis, and Candida parapsilosis and antibacterial activity against human pathogenic bacteria, including Escherichia fergusonii, Staphylococcus aureus, Salmonella enterica, Enterococcus faecalis, Bacillus cereus and Pseudomonas aeruginosa. The purification procedure entailed ethyl acetate extract, silica gel column, and thin layer chromatography. Based on 1H NMR metabolomic procedure application, also supported by the GC-MS analysis, cyclic dipeptide (l-Leucyl-l-Proline) was identified as the major compound in the bioactive fraction. In order to confirm the identity of the active compound and to have a large quantity thereof, a chemical synthesis of the cyclic dipeptide was performed. The synthetic compound was obtained with a very good yield (50%) and presented almost the same effect compared to the extracted fraction. This study indicates for the first time that Streptomyces misionensis V16R3Y1 exhibits a broad spectrum of antimicrobial activities, produced cyclic dipeptide (l-Leucyl-l-Proline) and might have potential use as a natural agent for pharmaceutical and agri-food applications. Full article
(This article belongs to the Special Issue Peptide Antibiotics from Microbes and Venomous Animals)
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Open AccessArticle
The Israeli Phage Bank (IPB)
Antibiotics 2020, 9(5), 269; https://doi.org/10.3390/antibiotics9050269 - 21 May 2020
Viewed by 1173
Abstract
A key element in phage therapy is the establishment of large phage collections, termed herein “banks”, where many well-characterized phages, ready to be used in the clinic, are stored. These phage banks serve for both research and clinical purposes. Phage banks are also [...] Read more.
A key element in phage therapy is the establishment of large phage collections, termed herein “banks”, where many well-characterized phages, ready to be used in the clinic, are stored. These phage banks serve for both research and clinical purposes. Phage banks are also a key element in clinical phage microbiology, the prior treatment matching of phages and antibiotics to specific bacterial targets. A worldwide network of phage banks can promote a phage-based solution for any isolated bacteria. Herein, we describe the Israeli Phage Bank (IPB) established in the Hebrew University, Jerusalem, which currently has over 300 phages matching 16 bacteria, mainly pathogens. The phage bank is constantly isolating new phages and developing methods for phage isolation and characterization. The information on the phages and bacteria stored in the bank is available online. Full article
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Open AccessReview
Phages for Biofilm Removal
Antibiotics 2020, 9(5), 268; https://doi.org/10.3390/antibiotics9050268 - 21 May 2020
Viewed by 954
Abstract
Biofilms are clusters of bacteria that live in association with surfaces. Their main characteristic is that the bacteria inside the biofilms are attached to other bacterial cells and to the surface by an extracellular polymeric matrix. Biofilms are capable of adhering to a [...] Read more.
Biofilms are clusters of bacteria that live in association with surfaces. Their main characteristic is that the bacteria inside the biofilms are attached to other bacterial cells and to the surface by an extracellular polymeric matrix. Biofilms are capable of adhering to a wide variety of surfaces, both biotic and abiotic, including human tissues, medical devices, and other materials. On these surfaces, biofilms represent a major threat causing infectious diseases and economic losses. In addition, current antibiotics and common disinfectants have shown limited ability to remove biofilms adequately, and phage-based treatments are proposed as promising alternatives for biofilm eradication. This review analyzes the main advantages and challenges that phages can offer for the elimination of biofilms, as well as the most important factors to be taken into account in order to design effective phage-based treatments. Full article
(This article belongs to the Special Issue Phage Therapy, Lysin Therapy, and Antibiotics, a Trio Due to Come)
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Open AccessArticle
In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type β-Lactamase Inhibitor, GT-055, against Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Panel Strains
Antibiotics 2020, 9(5), 267; https://doi.org/10.3390/antibiotics9050267 - 20 May 2020
Viewed by 720
Abstract
This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-β-lactam [...] Read more.
This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-β-lactam β-lactamase inhibitor (BLI) of diazabicyclooctane, GT-055, (also referred to as LCB18-055) against molecularly characterised resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. isolates. GT-1 and GT-1/GT-055 were tested in vitro against comparators among three different characterised panel strain sets. Bacterial resistome and siderophore uptake systems were characterised to elucidate the genetic basis for GT-1 minimum inhibitory concentrations (MICs). GT-1 exhibited in vitro activity (≤2 μg/mL MICs) against many MDR isolates, including extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing E. coli and K. pneumoniae and oxacillinase (OXA)-producing Acinetobacter spp. GT-1 also inhibited strains with mutated siderophore transporters and porins. Although BLI GT-055 exhibited intrinsic activity (MIC 2–8 μg/mL) against most E. coli and K. pneumoniae isolates, GT-055 enhanced the activity of GT-1 against many GT-1–resistant strains. Compared with CAZ-AVI, GT-1/GT-055 exhibited lower MICs against E. coli and K. pneumoniae isolates. GT-1 demonstrated potent in vitro activity against clinical panel strains of E. coli, K. pneumoniae and Acinetobacter spp. GT-055 enhanced the in vitro activity of GT-1 against many GT-1–resistant strains. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
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Open AccessArticle
Examining Safety of Biocolourants from Fungal and Plant Sources-Examples from Cortinarius and Tapinella, Salix and Tanacetum spp. and Dyed Woollen Fabrics
Antibiotics 2020, 9(5), 266; https://doi.org/10.3390/antibiotics9050266 - 20 May 2020
Viewed by 874
Abstract
Biocolourants have been investigated as alternatives to synthetic dyes. However, natural origin per se is not a label of harmlessness and research is needed to obtain safe dyes. We studied the cytotoxicity of the extracts from fungal (Cortinarius semisanguineus, Tapinella atrotomentosa [...] Read more.
Biocolourants have been investigated as alternatives to synthetic dyes. However, natural origin per se is not a label of harmlessness and research is needed to obtain safe dyes. We studied the cytotoxicity of the extracts from fungal (Cortinarius semisanguineus, Tapinella atrotomentosa) and plant (Tanacetum vulgare, Salix phylicifolia) sources and the woollen fabrics dyed with the extracts. Cytotoxicity in vitro using hepa-1 mouse hepatoma cells for 24 h and 72 h exposure was observed as the highest tolerated dose. All biocolourants produced intensive colour on fabrics with fastness properties from moderate to good. The Salix and Cortinarius samples did not show any cytotoxic effects, whereas the Tanacetum and Tapinella samples had slightly higher test values but were not interpreted as being significantly toxic. Higher than zero values of the undyed fabrics showed the importance of examining their toxicity as well. It was found that the cytotoxicity of the samples dyed with the biocolourants did not differ significantly from the undyed wool fabric. The concentrations of dyes used in the assays were very low, imitating the dose of the user. In addition to colouring properties, natural dyes may have pharmaceutical and antibacterial properties which would enhance the interest in using them in products for added value. Full article
(This article belongs to the Special Issue Fungal Secondary Metabolites)
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Open AccessArticle
Infectious Disease and Primary Care Research—What English General Practitioners Say They Need
Antibiotics 2020, 9(5), 265; https://doi.org/10.3390/antibiotics9050265 - 20 May 2020
Viewed by 656
Abstract
Background: Infections are one of the most common reasons for patients attending primary care. Antimicrobial resistance (AMR) is perhaps one of the biggest threats to modern medicine; data show that 81% of antibiotics in the UK are prescribed in primary care. Aim: To [...] Read more.
Background: Infections are one of the most common reasons for patients attending primary care. Antimicrobial resistance (AMR) is perhaps one of the biggest threats to modern medicine; data show that 81% of antibiotics in the UK are prescribed in primary care. Aim: To identify where the perceived gaps in knowledge, skills, guidance and research around infections and antibiotic use lie from the general practitioner (GP) viewpoint. Design and Setting: An online questionnaire survey. Method: The survey, based on questions asked of Royal College of General Practitioners (RCGP) members in 1999, and covering letter were electronically sent to GPs between May and August 2017 via various primary care dissemination routes. Results: Four hundred and twenty-eight GPs responded. Suspected Infection in the elderly, recurrent urinary tract infection (UTI), surveillance of AMR in the community, leg ulcers, persistent cough and cellulitis all fell into the top six conditions ranked in order of importance that require further research, evidence and guidance. Acute sore throat, otitis media and sinusitis were of lower importance than in 1999. Conclusion: This survey will help the NHS, the UK National Institute for Health and Care Excellence (NICE) and researchers to prioritise for the development of guidance and research for chronic conditions highlighted for which there is little evidence base for diagnostic and management guidelines in primary care. In contrast, 20 years of investment into research, guidance and resources for acute respiratory infections have successfully reduced these as priority areas for GPs. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship in Primary Care)
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Open AccessArticle
whISOBAXTM Inhibits Bacterial Pathogenesis and Enhances the Effect of Antibiotics
Antibiotics 2020, 9(5), 264; https://doi.org/10.3390/antibiotics9050264 - 19 May 2020
Viewed by 688
Abstract
As bacteria are becoming more resistant to commonly used antibiotics, alternative therapies are being sought. whISOBAX (WH) is a witch hazel extract that is highly stable (tested up to 2 months in 37 °C) and contains a high phenolic content, where 75% of [...] Read more.
As bacteria are becoming more resistant to commonly used antibiotics, alternative therapies are being sought. whISOBAX (WH) is a witch hazel extract that is highly stable (tested up to 2 months in 37 °C) and contains a high phenolic content, where 75% of it is hamamelitannin and traces of gallic acid. Phenolic compounds like gallic acid are known to inhibit bacterial growth, while hamamelitannin is known to inhibit staphylococcal pathogenesis (biofilm formation and toxin production). WH was tested in vitro for its antibacterial activity against clinically relevant Gram-positive and Gram-negative bacteria, and its synergy with antibiotics determined using checkerboard assays followed by isobologram analysis. WH was also tested for its ability to suppress staphylococcal pathogenesis, which is the cause of a myriad of resistant infections. Here we show that WH inhibits the growth of all bacteria tested, with variable efficacy levels. The most WH-sensitive bacteria tested were Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis, followed by Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Streptococcus agalactiae and Streptococcus pneumoniae. Furthermore, WH was shown on S. aureus to be synergistic to linezolid and chloramphenicol and cumulative to vancomycin and amikacin. The effect of WH was tested on staphylococcal pathogenesis and shown here to inhibit biofilm formation (tested on S. epidermidis) and toxin production (tested on S. aureus Enterotoxin A (SEA)). Toxin inhibition was also evident in the presence of subinhibitory concentrations of ciprofloxacin that induces pathogenesis. Put together, our study indicates that WH is very effective in inhibiting the growth of multiple types of bacteria, is synergistic to antibiotics, and is also effective against staphylococcal pathogenesis, often the cause of persistent infections. Our study thus suggests the benefits of using WH to combat various types of bacterial infections, especially those that involve resistant persistent bacterial pathogens. Full article
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Open AccessArticle
Community-Acquired and Healthcare-Associated Sepsis: Characteristics and in-Hospital Mortality in Italy
Antibiotics 2020, 9(5), 263; https://doi.org/10.3390/antibiotics9050263 - 19 May 2020
Viewed by 703
Abstract
Background: The main aim of the study was to analyse characteristics of sepsis according to the setting of occurrence and to identify predictors of sepsis-related in-hospital mortality. Methods: 544 medical records of adult patients with a diagnosis of sepsis were consulted [...] Read more.
Background: The main aim of the study was to analyse characteristics of sepsis according to the setting of occurrence and to identify predictors of sepsis-related in-hospital mortality. Methods: 544 medical records of adult patients with a diagnosis of sepsis were consulted and divided into two groups according to the setting where sepsis originated: community-acquired (CA) and healthcare-associated (HA) sepsis. Results: Overall, 257 (47.2%) patients had HA sepsis and the in-hospital death rate was 33.6%. Results of the multiple logistic regression revealed that patients with HA sepsis were significantly more likely to have been admitted from another hospital or ward, to have a ≥1 Charlson’s index, to be immunesuppressed, and to have undergone a surgical intervention during hospitalization. In-hospital deaths were significantly associated with older age, admission from another hospital or ward, need of haemodialysis and mechanical ventilation (MV), whereas they were less likely in patients with HA sepsis as compared with CA sepsis. Conclusion: Community-acquired and HA sepsis show distinct clinical, prognostic and risk factors profiles, and should be managed according to their differential characteristics. Full article
Open AccessArticle
Antagonistic Activity against Ascosphaera apis and Functional Properties of Lactobacillus kunkeei Strains
Antibiotics 2020, 9(5), 262; https://doi.org/10.3390/antibiotics9050262 - 18 May 2020
Viewed by 729
Abstract
Lactic acid bacteria (LAB) are an important group of honeybee gut microbiota. These bacteria are involved in food digestion, stimulate the immune system, and may antagonize undesirable microorganisms in the gastrointestinal tract. Lactobacillus kunkeei is a fructophilic lactic acid bacterium (FLAB) most frequently [...] Read more.
Lactic acid bacteria (LAB) are an important group of honeybee gut microbiota. These bacteria are involved in food digestion, stimulate the immune system, and may antagonize undesirable microorganisms in the gastrointestinal tract. Lactobacillus kunkeei is a fructophilic lactic acid bacterium (FLAB) most frequently found in the gastrointestinal tracts of honeybees. Ascosphaera apis is an important pathogenic fungus of honeybee larvae; it can colonize the intestine, especially in conditions of nutritional or environmental stress that cause microbial dysbiosis. In this work, some functional properties of nine selected L. kunkeei strains were evaluated. The study focused on the antifungal activity of these strains against A. apis DSM 3116, using different matrices: cell lysate, broth culture, cell-free supernatant, and cell pellet. The cell lysate showed the highest antifungal activity. Moreover, the strains were shown to possess good cell-surface properties (hydrophobicity, auto-aggregation, and biofilm production) and a good resistance to high sugar concentrations. These L. kunkeei strains were demonstrated to be functional for use in “probiotic syrup”, useful to restore the symbiotic communities of the intestine in case of dysbiosis and to exert a prophylactic action against A. apis. Full article
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Open AccessArticle
Molecular Typing, Characterization of Antimicrobial Resistance, Virulence Profiling and Analysis of Whole-Genome Sequence of Clinical Klebsiella pneumoniae Isolates
Antibiotics 2020, 9(5), 261; https://doi.org/10.3390/antibiotics9050261 - 17 May 2020
Viewed by 736
Abstract
Klebsiella pneumoniae is one of the most important pathogens concerned with multidrug resistance in healthcare-associated infections. The treating of infections caused by this bacterium is complicated due to the emergence and rapid spreading of carbapenem-resistant strains, which are associated with high mortality rates. [...] Read more.
Klebsiella pneumoniae is one of the most important pathogens concerned with multidrug resistance in healthcare-associated infections. The treating of infections caused by this bacterium is complicated due to the emergence and rapid spreading of carbapenem-resistant strains, which are associated with high mortality rates. Recently, several hypervirulent and carbapenemase-producing isolates were reported that make the situation even more complicated. In order to better understand the resistance and virulence mechanisms, and, in turn, to develop effective treatment strategies for the infections caused by multidrug-resistant K. pneumoniae, more comprehensive genomic and phenotypic data are required. Here, we present the first detailed molecular epidemiology report based on second and third generation (long-read) sequencing for the clinical isolates of K. pneumoniae in the Russian Federation. The data include three schemes of molecular typing, phenotypic and genotypic antibiotic resistance determination, as well as the virulence and plasmid profiling for 36 K. pneumoniae isolates. We have revealed 2 new multilocus sequence typing (MLST)-based sequence types, 32 multidrug-resistant (MDR) isolates and 5 colistin-resistant isolates in our samples. Three MDR isolates belonged to a very rare ST377 type. The whole genome sequences and additional data obtained will greatly facilitate further investigations in the field of antimicrobial resistance studies. Full article
(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)
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Open AccessArticle
Effect of Biosynthesized ZnO Nanoparticles on Multi-Drug Resistant Pseudomonas Aeruginosa
Antibiotics 2020, 9(5), 260; https://doi.org/10.3390/antibiotics9050260 - 17 May 2020
Viewed by 783
Abstract
Synthesis of nanoparticles using the plants has several advantages over other methods due to the environmentally friendly nature of plants. Besides being environmentally friendly, the synthesis of nanoparticles using plants or parts of the plants is also cost effective. The present study focuses [...] Read more.
Synthesis of nanoparticles using the plants has several advantages over other methods due to the environmentally friendly nature of plants. Besides being environmentally friendly, the synthesis of nanoparticles using plants or parts of the plants is also cost effective. The present study focuses on the biosynthesis of zinc oxide nanoparticles (ZnO NPs) using the seed extract of Butea monsoperma and their effect on to the quorum-mediated virulence factors of multidrug-resistant clinical isolates of Pseudomonas aeruginosa at sub minimum inhibitory concentration (MIC). The synthesized ZnO NPs were characterized by different techniques, such as Fourier transform infra-red spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), and transmission electron microscopy (TEM). The average size of the nanoparticles was 25 nm as analyzed by TEM. ZnO NPs at sub MIC decreased the production of virulence factors such as pyocyanin, protease and hemolysin for P. aeruginosa (p ≤ 0.05). The interaction of NPs with the P. aeruginosa cells on increasing concentration of NPs at sub MIC levels showed greater accumulation of nanoparticles inside the cells as analyzed by TEM. Full article
(This article belongs to the Special Issue New Materials for Antibacterial Applications)
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Open AccessReview
Detection of Quorum-Sensing Molecules for Pathogenic Molecules Using Cell-Based and Cell-Free Biosensors
Antibiotics 2020, 9(5), 259; https://doi.org/10.3390/antibiotics9050259 - 16 May 2020
Viewed by 748
Abstract
Since the discovery and subsequent use of penicillin, antibiotics have been used to treat most bacterial infections in the U.S. Over time, the repeated prescription of many antibiotics has given rise to many antibiotic-resistant microbes. A bacterial strain becomes resistant by horizontal gene [...] Read more.
Since the discovery and subsequent use of penicillin, antibiotics have been used to treat most bacterial infections in the U.S. Over time, the repeated prescription of many antibiotics has given rise to many antibiotic-resistant microbes. A bacterial strain becomes resistant by horizontal gene transfer, where surviving microbes acquire genetic material or DNA fragments from adjacent bacteria that encode for resistance. In order to avoid significant bacterial resistance, novel and target therapeutics are needed. Further advancement of diagnostic technologies could be used to develop novel treatment strategies. The use of biosensors to detect quorum-sensing signaling molecules has the potential to provide timely diagnostic information toward mitigating the multidrug-resistant bacteria epidemic. Resistance and pathogenesis are controlled by quorum-sensing (QS) circuits. QS systems secrete or passively release signaling molecules when the bacterial concentration reaches a certain threshold. Signaling molecules give an early indication of virulence. Detection of these compounds in vitro or in vivo can be used to identify the onset of infection. Whole-cell and cell-free biosensors have been developed to detect quorum-sensing signaling molecules. This review will give an overview of quorum networks in the most common pathogens found in chronic and acute infections. Additionally, the current state of research surrounding the detection of quorum-sensing molecules will be reviewed. Followed by a discussion of future works toward the advancement of technologies to quantify quorum signaling molecules in chronic and acute infections. Full article
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Open AccessArticle
New Insights into Bioactive Compounds from the Medicinal Plant Spathodea campanulata P. Beauv. and Their Activity against Helicobacter pylori
Antibiotics 2020, 9(5), 258; https://doi.org/10.3390/antibiotics9050258 - 15 May 2020
Viewed by 620
Abstract
The medicinal plant Spathodea campanulata P. Beauv. (Bignoniaceae) has been traditionally applied for the prevention and treatment of diseases of the kidney and urinary system, the skin, the gastrointestinal tract, and inflammation in general. The present work shows for the first time how [...] Read more.
The medicinal plant Spathodea campanulata P. Beauv. (Bignoniaceae) has been traditionally applied for the prevention and treatment of diseases of the kidney and urinary system, the skin, the gastrointestinal tract, and inflammation in general. The present work shows for the first time how chemical components from this plant inhibit Helicobacter pylori growth by urease inhibition and modulation of virulence factors. The crude extract and the main fractions of S. campanulata bark were tested on H. pylori isolated strains and the active ones were further fractionated. Fractions and sub-fractions of the plant crude extract were characterized by ultra-high-performance liquid chromatographic tandem high resolution-mass spectrometry detection (UHPLC-HRMS). Several phenolics and triterpenoids were identified. Among the sub-fractions obtained, SB2 showed the capacity to inhibit H. pylori urease in a heterologous bacterial model. One additional sub-fraction (SE3) was able to simultaneously modulate the expression of two adhesins (HopZ and BabA) and one cytotoxin (CagA). The flavonol kaempferol was identified as the most interesting compound that deserves further investigation as a new hit for its capacity to modulate H. pylori virulence factors. Full article
(This article belongs to the Special Issue Novel Targets and Mechanisms in Antimicrobial Drug Discovery)
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Open AccessArticle
Activity of Bacteriophage and Complex Tannins against Biofilm-Forming Shiga Toxin-Producing Escherichia coli from Canada and South Africa
Antibiotics 2020, 9(5), 257; https://doi.org/10.3390/antibiotics9050257 - 15 May 2020
Viewed by 671
Abstract
Bacteriophages, natural killers of bacteria, and plant secondary metabolites, such as condensed tannins, are potential agents for the control of foodborne pathogens. The first objective of this study evaluated the efficacy of a bacteriophage SA21RB in reducing pre-formed biofilms on stainless-steel produced by [...] Read more.
Bacteriophages, natural killers of bacteria, and plant secondary metabolites, such as condensed tannins, are potential agents for the control of foodborne pathogens. The first objective of this study evaluated the efficacy of a bacteriophage SA21RB in reducing pre-formed biofilms on stainless-steel produced by two Shiga toxin-producing Escherichia coli (STEC) strains, one from South Africa and the other from Canada. The second objective examined the anti-bacterial and anti-biofilm activity of condensed tannin (CT) from purple prairie clover and phlorotannins (PT) from brown seaweed against these strains. For 24-h-old biofilms, (O113:H21; 6.2 log10 colony-forming units per square centimeter (CFU/cm2) and O154:H10; 5.4 log10 CFU/cm2), 3 h of exposure to phage (1013 plaque-forming units per milliliter (PFU/mL)) reduced (p ≤ 0.05) the number of viable cells attached to stainless-steel coupons by 2.5 and 2.1 log10 CFU/cm2 for O113:H21 and O154:H10, respectively. However, as biofilms matured, the ability of phage to control biofilm formation declined. In biofilms formed for 72 h (O113:H21; 5.4 log10 CFU/cm2 and O154:H10; 7 log10 CFU/cm2), reductions after the same duration of phage treatment were only 0.9 and 1.3 log10 CFU/cm2 for O113:H21 and O154:H10, respectively. Initial screening of CT and PT for anti-bacterial activity by a microplate assay indicated that both STEC strains were less sensitive (p ≤ 0.05) to CT than PT over a concentration range of 25–400 µg/mL. Based on the lower activity of CT (25–400 µg/mL), they were not further examined. Accordingly, PT (50 µg/mL) inhibited (p ≤ 0.05) biofilm formation for up to 24 h of incubation at 22 °C, but this inhibition progressively declined over 72 h for both O154:H10 and O113:H21. Scanning electron microscopy revealed that both SA21RB and PT eliminated 24 h biofilms, but that both strains were able to adhere and form biofilms on stainless-steel coupons at longer incubation times. These findings revealed that phage SA21RB is more effective at disrupting 24 than 72 h biofilms and that PT were able to inhibit biofilm formation of both E. coli O154:H10 and O113:H21 for up to 24 h. Full article
(This article belongs to the Special Issue Pathogenic Escherichia coli: Infections and Therapies)
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Open AccessArticle
One-Step Differential Detection of OXA-48-Like Variants Using High-Resolution Melting (HRM) Analysis
Antibiotics 2020, 9(5), 256; https://doi.org/10.3390/antibiotics9050256 - 15 May 2020
Viewed by 577
Abstract
OXA-48-like carbapenemase gene remains a hidden threat, as different OXA-48 variants have varying presentations of susceptibility to antibiotics that might affect the treatment decisions. Rapid detection and differentiation of OXA-48-like carbapenemase genes are critical for targeted treatment and infection control. In this study, [...] Read more.
OXA-48-like carbapenemase gene remains a hidden threat, as different OXA-48 variants have varying presentations of susceptibility to antibiotics that might affect the treatment decisions. Rapid detection and differentiation of OXA-48-like carbapenemase genes are critical for targeted treatment and infection control. In this study, we aimed to develop high-resolution melting (HRM) analysis for the differentiation of OXA-48 variants. HRM analysis is a post-polymerase chain reaction (post-PCR) method for identification of small variations in nucleic acid sequences based on the PCR dissociation curve. A total of 82 bacterial strains, which consisted of Enterobacteriaceae and non-Enterobacteriaceae, were collected from a tertiary teaching hospital. The sensitivity and specificity of the assay were determined, and the developed assay was evaluated using the collected isolates against conventional-sequencing method. Overall, the developed assay was able to detect isolates that harboured OXA-48 and OXA232/OXA-181 by showing two distinct peaks at 81.1 ± 0.2 °C and 82.1 ± 0.2 °C, respectively. The detection limit of the assay was 1.6 x 10−6 ng/µL for OXA-48 and 1.8 × 10−7 ng/µL for OXA-232/OXA-181. This assay showed 100% specificity when evaluated on a panel of 37 isolates comprised of different species of bacteria and yeasts. When the assay with isolates collected in the year 2016 was first evaluated, the assay showed comparable results with conventional PCR-sequencing method where 34 OXA-48 and OXA-232/OXA-181 were detected. By using HRM analysis, the presence of OXA-48-like variants could be easily identified within 3 h from the pure culture. Full article
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Open AccessPerspective
Optimizing Anti-Viral Vaccine Responses: Input from a Non-Specialist
Antibiotics 2020, 9(5), 255; https://doi.org/10.3390/antibiotics9050255 - 15 May 2020
Viewed by 950
Abstract
Recently, the research community has had a real-world look at reasons for improving vaccine responses to emerging RNA viruses. Here, a vaccine non-specialist suggests how this might be done. I propose two alternative options and compare the primary alternative option with current practice. [...] Read more.
Recently, the research community has had a real-world look at reasons for improving vaccine responses to emerging RNA viruses. Here, a vaccine non-specialist suggests how this might be done. I propose two alternative options and compare the primary alternative option with current practice. The basis of comparison is feasibility in achieving what we need: a safe, mass-produced, emerging virus-targeted vaccine on 2–4 week notice. The primary option is the following. (1) Start with a platform based on live viruses that infect bacteria, but not humans (bacteriophages, or phages). (2) Isolate phages (to be called pathogen homologs) that resemble and provide antigenic context for membrane-covered, pathogenic RNA viruses; coronavirus-phage homologs will probably be found if the search is correctly done. (3) Upon isolating a viral pathogen, evolve its phage homolog to bind antibodies neutralizing for the viral pathogen. Vaccinate with the evolved phage homolog by generating a local, non-hazardous infection with the phage host and then curing the infection by propagating the phage in the artificially infecting bacterial host. I discuss how this alternative option has the potential to provide what is needed after appropriate platforms are built. Full article
(This article belongs to the Special Issue Phage Diversity for Research and Application)
Open AccessArticle
Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species
Antibiotics 2020, 9(5), 254; https://doi.org/10.3390/antibiotics9050254 - 14 May 2020
Cited by 1 | Viewed by 2084
Abstract
Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes [...] Read more.
Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51–1.72) in multivariable Cox proportional hazards regression analysis. Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents. Full article
(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)
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Open AccessArticle
Self-Reported Antimicrobial Stewardship Practices in Primary Care Using the TARGET Antibiotics Self-Assessment Tool
Antibiotics 2020, 9(5), 253; https://doi.org/10.3390/antibiotics9050253 - 14 May 2020
Viewed by 635
Abstract
The self-assessment tool (SAT) is a 16-question self-report of antimicrobial stewardship practices in primary care, available in the TARGET (Treat Antibiotics Responsibly, Guidance Education and Tools) Antibiotics Toolkit. This study analysed responses to the SAT and compared them to previous SAT data (2014–2016). [...] Read more.
The self-assessment tool (SAT) is a 16-question self-report of antimicrobial stewardship practices in primary care, available in the TARGET (Treat Antibiotics Responsibly, Guidance Education and Tools) Antibiotics Toolkit. This study analysed responses to the SAT and compared them to previous SAT data (2014–2016). Data from June 2016 to September 2019 were anonymised and analysed using Microsoft Excel and STATA 15. Clinicians reported engaging in positive antimicrobial stewardship (AMS) practices including using antibiotic guidance to inform treatment decisions (98%, 98% 2014–2016), discussing antibiotic prescribing within the practice (73%, 67% 2014–2016), using patient-facing resources (94%, 71% 2014–2016), conducting antibiotic audits in the last two years (98%, 45% 2014–2016), keeping written records and action plans (81%, 62% 2014–2016), using back-up prescribing (99%, 94% 2014–2016) and using clinical coding (80%, 75% 2014–2016). Areas for improvement include developing strategies to avoid patients reconsulting to obtain antibiotics (45%, 33% 2014–2016), undertaking infection-related learning (37%, 29% 2014–2016), ensuring all temporary prescribers have access to antibiotic guidance (55%, 63% 2014–2016) and making patient information leaflets easily available during consultations (31%). The findings offer a unique insight into AMS in primary care over time. The SAT gives primary care clinicians and commissioners an opportunity to reflect on their AMS and learning. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship in Primary Care)
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Open AccessCommunication
Mersaquinone, A New Tetracene Derivative from the Marine-Derived Streptomyces sp. EG1 Exhibiting Activity against Methicillin-Resistant Staphylococcus aureus (MRSA)
Antibiotics 2020, 9(5), 252; https://doi.org/10.3390/antibiotics9050252 - 14 May 2020
Viewed by 718
Abstract
New antibiotics are desperately needed to overcome the societal challenges being encountered with methicillin-resistant Staphylococcus aureus (MRSA). In this study, a new tetracene derivative, named Mersaquinone (1), and the known Tetracenomycin D (2), Resistoflavin (3) and Resistomycin [...] Read more.
New antibiotics are desperately needed to overcome the societal challenges being encountered with methicillin-resistant Staphylococcus aureus (MRSA). In this study, a new tetracene derivative, named Mersaquinone (1), and the known Tetracenomycin D (2), Resistoflavin (3) and Resistomycin (4) have been isolated from the organic extract of the marine Streptomyces sp. EG1. The strain was isolated from a sediment sample collected from the North Coast of the Mediterranean Sea of Egypt. The chemical structure of Mersaquinone (1) was assigned based upon data from a diversity of spectroscopic techniques including HRESIMS, IR, 1D and 2D NMR measurements. Mersaquinone (1) showed antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of 3.36 μg/mL. Full article
(This article belongs to the Special Issue Antibacterial Drug Discovery)
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Open AccessFeature PaperArticle
Antimicrobial Resistance Profiles of Adherent Invasive Escherichia coli Show Increased Resistance to β-Lactams
Antibiotics 2020, 9(5), 251; https://doi.org/10.3390/antibiotics9050251 - 13 May 2020
Viewed by 760
Abstract
The adherent invasive Escherichia coli (AIEC) pathotype has been associated with the aetiology of Crohn’s disease (CD). Scarce reports have shown the antimicrobial resistance (AMR) profiles of AIEC. Despite antibiotics not being recommended to treat CD, antimicrobial therapy could be useful in stratified [...] Read more.
The adherent invasive Escherichia coli (AIEC) pathotype has been associated with the aetiology of Crohn’s disease (CD). Scarce reports have shown the antimicrobial resistance (AMR) profiles of AIEC. Despite antibiotics not being recommended to treat CD, antimicrobial therapy could be useful in stratified patients, such as AIEC carriers. We examined the antimicrobial resistance profiles of AIEC strains to identify which therapies could be effective or confer a risk for such patients. Phenotypic resistance to 30 antimicrobials was tested according to CLSI standards. AIEC (n = 22) and non-pathogenic E. coli (non-AIEC) strains (n = 37) isolated from the gut mucosa of 31 CD patients and 18 controls were studied. De novo genome sequencing was carried out for 39 of the 59 strains, and AMR genes were searched using the DeepARG database in these genomes and 33 additional AIEC publicly available genomes. The strains isolated from CD and controls showed similar phenotypic AMR profiles. The genomic analysis did not reveal an increased prevalence of AMR genes. However, AIEC strains were more frequently resistant to β-lactams than non-AIEC strains (11 AIEC (50%) and 5 non-AIEC (22%) strains were resistant to at least one β-lactam; p < 0.042). Two AIEC strains were resistant to expanded-spectrum cephalosporins. One strain carried a plasmid-mediated AmpC β-lactamase (CMY-69), and the other presented mutations in the promotor of the intrinsic chromosomal AmpC related to the hyperproduction of this enzyme. The rest of the strains were resistant to β-lactams not including expanded-spectrum cephalosporins. The majority carried TEM-related β-lactamases. Genomic analysis including external AIEC revealed that the gene sul1 encoding for sulphonamide resistance was more frequent in AIEC strains than non-AIEC strains (34.6% vs. 9.5%, p = 0.030). AMR in AIEC is a matter of concern regarding the putative implication of the pathotype in CD. The high proportion of AIEC resistant to β-lactams warrants caution about the risk there may be in the use of these antimicrobials in AIEC-colonized CD patients. Full article
(This article belongs to the Special Issue Pathogenic Escherichia coli: Infections and Therapies)
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Open AccessArticle
Discontinuation of Glycopeptides in Patients with Culture Negative Severe Sepsis or Septic Shock: A Propensity-Matched Retrospective Cohort Study
Antibiotics 2020, 9(5), 250; https://doi.org/10.3390/antibiotics9050250 - 13 May 2020
Viewed by 590
Abstract
Implementation of antibiotic stewardship is difficult in patients with sepsis because of severity of disease. We evaluated the impact of glycopeptide discontinuation (GD) in patients with culture negative severe sepsis or septic shock who received glycopeptides as initial empiric antibiotic therapy at admission. [...] Read more.
Implementation of antibiotic stewardship is difficult in patients with sepsis because of severity of disease. We evaluated the impact of glycopeptide discontinuation (GD) in patients with culture negative severe sepsis or septic shock who received glycopeptides as initial empiric antibiotic therapy at admission. We conducted a single center retrospective cohort study between January 2010 and March 2018. GD was defined as discontinuation of initial empiric glycopeptides on availability of culture results, revealing the absence of identified pathogens. In 92 included patients, the leading causes of sepsis were pneumonia (34.8%) and intra-abdominal infection (23.9%); 28-day mortality and overall mortality were 14% and 21%, respectively. Glycopeptides were discontinued in 42/92 patients. After propensity score matching, baseline characteristics were not significantly different between the GD and non-GD (GND) groups. GND was associated with development of acute kidney injury (OR 5.54, 95% CI 1.49–20.6, P = 0.011). GD did not increase the 7-day, 14-day, and 28-day mortality compared with GND. The length of hospital stay was shorter in the GD group than in GND group (16.33 ± 17.11 vs. 25.05 ± 14.37, P = 0.082), though not statistically significant. GD may be safe and reduce adverse events of prolonged antibiotic use in patients with culture negative severe sepsis or septic shock receiving glycopeptides as initial empiric antibiotic therapy. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessArticle
Isonitrile-Based Multicomponent Synthesis of β-Amino Boronic Acids as β-Lactamase Inhibitors
Antibiotics 2020, 9(5), 249; https://doi.org/10.3390/antibiotics9050249 - 12 May 2020
Cited by 1 | Viewed by 750
Abstract
The application of various isonitrile-based multicomponent reactions to protected (2-oxoethyl)boronic acid (as the carbonyl component) is described. The Ugi reaction, both in the four components and in the four centers–three components versions, and the van Leusen reaction, proved effective at providing small libraries [...] Read more.
The application of various isonitrile-based multicomponent reactions to protected (2-oxoethyl)boronic acid (as the carbonyl component) is described. The Ugi reaction, both in the four components and in the four centers–three components versions, and the van Leusen reaction, proved effective at providing small libraries of MIDA-protected β-aminoboronic acids. The corresponding free β-aminoboronic acids, quantitatively recovered through basic mild deprotection, were found to be quite stable and were fully characterized, including by 11B-NMR spectroscopy. Single-crystal X-ray diffraction analysis, applied both to a MIDA-protected and a free β-aminoboronic acid derivative, provided evidence for different conformations in the solid-state. Finally, the antimicrobial activities of selected compounds were evaluated by measuring their minimal inhibitory concentration (MIC) values, and the binding mode of the most promising derivative on OXA-23 class D β-lactamase was predicted by a molecular modeling study. Full article
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Open AccessArticle
Natural Oregano Essential Oil May Replace Antibiotics in Lamb Diets: Effects on Meat Quality
Antibiotics 2020, 9(5), 248; https://doi.org/10.3390/antibiotics9050248 - 12 May 2020
Cited by 1 | Viewed by 788
Abstract
A study was conducted to investigate the effect of oregano essential oil (OEO) and monensin sodium on the oxidative stability, colour, texture, and the fatty acid profile of lamb meat (m. Longissimus lumborum). Twenty Dorper x Pelibuey lambs were randomly divided into [...] Read more.
A study was conducted to investigate the effect of oregano essential oil (OEO) and monensin sodium on the oxidative stability, colour, texture, and the fatty acid profile of lamb meat (m. Longissimus lumborum). Twenty Dorper x Pelibuey lambs were randomly divided into five treatments; control (CON), monensin sodium (SM, Rumensin 200® 33 mg/kg), a low level of OEO (LO, 0.2 g/kg dry matter (DM)), a medium level of OEO (MO, 0.3g/ kg DM), and a high level of OEO (HO, 0.4 g/kg DM). Dietary supplementation of OEO at any concentration lowered the compression strength in comparison with CON and SM. MO had the highest a* values (7.99) and fatty acid concentration (C16:1n7, C18:1n9c, C18:1n6c, C20:1n9, and C18:2n6c) during storage for 7 d at 3 °C. Lipid oxidation was not promoted (p > 0.05) by the moderated supplementation of oregano essential oil; however, OEO at 0.3 g/kg DM showed a slight lipid pro-oxidant effect. Dietary supplementation of MO and SM had the same effect on colour, tenderness, and the fatty acid profile of lamb (L. lumborum). It was demonstrated that oregano essential oil was beneficial for lambs feeding, and it could be a natural alternative to replace monensin in lamb diets with improvements in the quality of the meat. Full article
(This article belongs to the Special Issue Chemical Composition and Biological Activities of Essential Oils)
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