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Antibiotics, Volume 10, Issue 1 (January 2021) – 95 articles

Cover Story (view full-size image): There is growing interest in the use of non-antibiotic treatments for common bacterial infections. One such option is the use of cranberry extract for urinary tract infections (UTIs). Cranberry extract contains proanthocyanidins with A-type linkages; these polyphenols, or their metabolites, are believed to be the active ingredient inhibiting the binding of Escherichia coli to the uroepithelium. Multiple studies have assessed the use of cranberry extract in the prevention of UTIs, with mixed results. Fewer studies have assessed the potential for cranberry extract to treat an acute UTI, despite many women using cranberry products for this indication. Through systematic review, the authors synthesize the evidence for the use of cranberry products in the management of acute, uncomplicated UTIs. View this paper.
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Open AccessArticle
Multidrug-Resistant Bacterial Infections in Geriatric Hospitalized Patients before and after the COVID-19 Outbreak: Results from a Retrospective Observational Study in Two Geriatric Wards
Antibiotics 2021, 10(1), 95; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010095 - 19 Jan 2021
Viewed by 517
Abstract
The impact of the COVID-19 pandemic on multidrug-resistant (MDR) bacteria is unknown. The purpose of this study was to assess prevalence, etiology, and association with mortality of MDR bacteria in older adult patients before and after the first peak of the COVID-19 pandemic [...] Read more.
The impact of the COVID-19 pandemic on multidrug-resistant (MDR) bacteria is unknown. The purpose of this study was to assess prevalence, etiology, and association with mortality of MDR bacteria in older adult patients before and after the first peak of the COVID-19 pandemic in Italy. An observational retrospective study was conducted in two geriatric wards of the Azienda Ospedaliera Ospedali Riuniti Marche Nord, Fano, and of the INRCA, IRCCS, Ancona, in the Marche Region, Italy, from December 2019 to February 2020 and from May to July 2020. A total of 73 patients (mean age 87.4 ± 5.9, 27.4% men) and 83 cultures (36 pre-COVID-19 and 47 post-COVID-19) were considered. Overall, 46 cultures (55.4%) reported MDR bacteria (50% in pre- and 59.6% in post-COVID-19 period, p = 0.384). MDR bacteria in bloodstream significantly increased in post-COVID-19 period (68.8% vs. 40.0% p = 0.038) and MDR bacteria in urine did not change (51.6 vs. 54.8%, p = 0.799). Escherichia coli was the main MDR bacterium in pre-COVID-19, p = 0.082 and post-COVID-19, p = 0.026. Among patients with MDR infection, in-hospital mortality was 37.5% and 68.8% in pre- and post-COVID-19, respectively (p = 0.104), and mortality at 30 days was higher in post-COVID-19 period (78.9% vs. 27.3%, p = 0.012). An increased number of MDR bacteria in bloodstream and mortality after MDR infection have been observed in the post-COVID-19 period. Full article
(This article belongs to the Special Issue Antibiotics Use and Antimicrobial Resistance in Hospital)
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Open AccessArticle
Drivers of Broad-Spectrum Antibiotic Overuse across Diverse Hospital Contexts—A Qualitative Study of Prescribers in the UK, Sri Lanka and South Africa
Antibiotics 2021, 10(1), 94; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010094 - 19 Jan 2021
Viewed by 654
Abstract
Antimicrobial stewardship programs focus on reducing overuse of broad-spectrum antibiotics (BSAs), primarily through interventions to change prescribing behavior. This study aims to identify multi-level influences on BSA overuse across diverse high and low income, and public and private, healthcare contexts. Semi-structured interviews were [...] Read more.
Antimicrobial stewardship programs focus on reducing overuse of broad-spectrum antibiotics (BSAs), primarily through interventions to change prescribing behavior. This study aims to identify multi-level influences on BSA overuse across diverse high and low income, and public and private, healthcare contexts. Semi-structured interviews were conducted with 46 prescribers from hospitals in the UK, Sri Lanka, and South Africa, including public and private providers. Interviews explored decision making about prescribing BSAs, drivers of the use of BSAs, and benefits of BSAs to various stakeholders, and were analyzed using a constant comparative approach. Analysis identified drivers of BSA overuse at the individual, social and structural levels. Structural drivers of overuse varied significantly across contexts and included: system-level factors generating tensions with stewardship goals; limited material resources within hospitals; and patient poverty, lack of infrastructure and resources in local communities. Antimicrobial stewardship needs to encompass efforts to reduce the reliance on BSAs as a solution to context-specific structural conditions. Full article
Open AccessArticle
Implementation of Antibiotic Stewardship in a University Hospital Setting
Antibiotics 2021, 10(1), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010093 - 19 Jan 2021
Cited by 1 | Viewed by 500
Abstract
The article describes activities of an antibiotic center at a university hospital in the Czech Republic and presents the results of antibiotic stewardship program implementation over a period of 10 years. It provides data on the development of resistance of Escherichia coli, [...] Read more.
The article describes activities of an antibiotic center at a university hospital in the Czech Republic and presents the results of antibiotic stewardship program implementation over a period of 10 years. It provides data on the development of resistance of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus to selected antibiotic agents as well as consumption data for various antibiotic classes. The genetic basis of resistance to beta-lactam antibiotics and its clonal spread were also assessed. The study showed significant correlations between aminoglycoside consumption and resistance of Escherichia coli and Klebsiella pneumoniae to gentamicin (r = 0.712, r = 0.869), fluoroquinolone consumption and resistance of Klebsiella pneumoniae to ciprofloxacin (r = 0.896), aminoglycoside consumption and resistance of Pseudomonas aeruginosa to amikacin (r = 0.716), as well as carbapenem consumption and resistance of Pseudomonas aeruginosa to meropenem (r = 0.855). Genotyping of ESBL- positive isolates of Klebsiella pneumoniae and Escherichia coli showed a predominance of CTX-M-type; in AmpC-positive strains, DHA, EBC and CIT enzymes prevailed. Of 19 meropenem-resistant strains of Klebsiella pneumoniae, two were identified as NDM-positive. Clonal spread of these strains was not detected. The results suggest that comprehensive antibiotic stewardship implementation in a healthcare facility may help to maintain the effectiveness of antibiotics against bacterial pathogens. Particularly beneficial is the work of clinical microbiologists who, among other things, approve administration of antibiotics to patients with bacterial infections and directly participate in their antibiotic therapy. Full article
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Open AccessReview
Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics
Antibiotics 2021, 10(1), 92; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010092 - 19 Jan 2021
Cited by 2 | Viewed by 544
Abstract
Antimicrobials have allowed medical advancements over several decades. However, the continuous emergence of antimicrobial resistance restricts efficacy in treating infectious diseases. In this context, the drug repositioning of already known biological active compounds to antimicrobials could represent a useful strategy. In 2002 and [...] Read more.
Antimicrobials have allowed medical advancements over several decades. However, the continuous emergence of antimicrobial resistance restricts efficacy in treating infectious diseases. In this context, the drug repositioning of already known biological active compounds to antimicrobials could represent a useful strategy. In 2002 and 2003, the SARS-CoV pandemic immobilized the Far East regions. However, the drug discovery attempts to study the virus have stopped after the crisis declined. Today’s COVID-19 pandemic could probably have been avoided if those efforts against SARS-CoV had continued. Recently, a new coronavirus variant was identified in the UK. Because of this, the search for safe and potent antimicrobials and antivirals is urgent. Apart from antiviral treatment for severe cases of COVID-19, many patients with mild disease without pneumonia or moderate disease with pneumonia have received different classes of antibiotics. Diarylureas are tyrosine kinase inhibitors well known in the art as anticancer agents, which might be useful tools for a reposition as antimicrobials. The first to come onto the market as anticancer was sorafenib, followed by some other active molecules. For this interesting class of organic compounds antimicrobial, antiviral, antithrombotic, antimalarial, and anti-inflammatory properties have been reported in the literature. These numerous properties make these compounds interesting for a new possible pandemic considering that, as well as for other viral infections also for CoVID-19, a multitarget therapeutic strategy could be favorable. This review is meant to be an overview on diarylureas, focusing on their biological activities, not dwelling on the already known antitumor activity. Quite a lot of papers present in the literature underline and highlight the importance of these molecules as versatile scaffolds for the development of new and promising antimicrobials and multitarget agents against new pandemic events. Full article
(This article belongs to the Special Issue Antibiotic Stewardship during COVID-19)
Open AccessReview
The Prospect of Repurposing Immunomodulatory Drugs for Adjunctive Chemotherapy against Tuberculosis: A Critical Review
Antibiotics 2021, 10(1), 91; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010091 - 19 Jan 2021
Viewed by 530
Abstract
Tuberculosis (TB) remains a global health emergency, with an estimated 2 billion people infected across the world, and 1.4 million people dying to this disease every year. Many aspects of the causative agent, Mycobacterium tuberculosis, make this disease difficult for healthcare and [...] Read more.
Tuberculosis (TB) remains a global health emergency, with an estimated 2 billion people infected across the world, and 1.4 million people dying to this disease every year. Many aspects of the causative agent, Mycobacterium tuberculosis, make this disease difficult for healthcare and laboratory researchers to fight against, such as unique pathophysiology, latent infection and long and complex treatment regimens, thus causing patient non-compliance with the treatment. Development of new drugs is critical for tackling these problems. Repurposing drugs is a promising strategy for generating an effective drug treatment whilst circumventing many of the challenges of conventional drug development. In this regard, the incorporation of immunomodulatory drugs into the standard regimen to potentiate frontline drugs is found to be highly appealing. Drugs of diverse chemical classes and drug categories are increasingly being evidenced to possess antitubercular activity, both in vitro and in vivo. This article explores and discusses the molecular entities that have shown promise in being repurposed for use in anti-TB adjunctive therapy and aims to provide the most up-to-date picture of their progress. Full article
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Open AccessArticle
Genome-Based Analyses of Fitness Effects and Compensatory Changes Associated with Acquisition of blaCMY-, blaCTX-M-, and blaOXA-48/VIM-1-Containing Plasmids in Escherichia coli
Antibiotics 2021, 10(1), 90; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010090 - 19 Jan 2021
Viewed by 408
Abstract
(1) Background: Resistance plasmids are under selective conditions beneficial for the bacterial host, but in the absence of selective pressure, this carriage may cause fitness costs. Compensation of this fitness burden is important to obtain competitive ability under antibiotic-free conditions. In this study, [...] Read more.
(1) Background: Resistance plasmids are under selective conditions beneficial for the bacterial host, but in the absence of selective pressure, this carriage may cause fitness costs. Compensation of this fitness burden is important to obtain competitive ability under antibiotic-free conditions. In this study, we investigated fitness effects after a conjugative transfer of plasmids containing various beta-lactamase genes transferred into Escherichia coli. (2) Methods: Fourteen beta-lactamase-encoding plasmids were transferred from clinical donor strains to E. coli J53. Growth rates were compared for all transconjugants and the recipient. Selected transconjugants were challenged in long-term growth experiments. Growth rates were assessed at different time points during growth for 500 generations. Whole-genome sequencing (WGS) of initial and evolved transconjugants was determined. Results: Most plasmid acquisitions resulted in growth differences, ranging from −4.5% to 7.2%. Transfer of a single blaCMY-16-carrying plasmid resulted in a growth burden and a growth benefit in independent mating. Long-term growth led to a compensation of fitness burdens and benefits. Analyzing WGS revealed genomic changes caused by Single Nucleotide Polymorphisms (SNPs) and insertion sequences over time. Conclusions: Fitness effects associated with plasmid acquisitions were variable. Potential compensatory mutations identified in transconjugants’ genomes after 500 generations give interesting insights into aspects of plasmid–host adaptations. Full article
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Open AccessReview
OXA-48 Carbapenemase-Producing Enterobacterales in Spanish Hospitals: An Updated Comprehensive Review on a Rising Antimicrobial Resistance
Antibiotics 2021, 10(1), 89; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010089 - 18 Jan 2021
Viewed by 608
Abstract
Carbapenemase-producing Enterobacterales (CPE) are significant contributors to the global public health threat of antimicrobial resistance. OXA-48-like enzymes and their variants are unique carbapenemases with low or null hydrolytic activity toward carbapenems but no intrinsic activity against expanded-spectrum cephalosporins. CPEs have been classified by [...] Read more.
Carbapenemase-producing Enterobacterales (CPE) are significant contributors to the global public health threat of antimicrobial resistance. OXA-48-like enzymes and their variants are unique carbapenemases with low or null hydrolytic activity toward carbapenems but no intrinsic activity against expanded-spectrum cephalosporins. CPEs have been classified by the WHO as high-priority pathogens given their association with morbidity and mortality and the scarce number of effective antibiotic treatments. In Spain, the frequency of OXA-48 CPE outbreaks is higher than in other European countries, representing the major resistance mechanism of CPEs. Horizontal transfer of plasmids and poor effective antibiotic treatment are additional threats to the correct prevention and control of these hospital outbreaks. One of the most important risk factors is antibiotic pressure, specifically carbapenem overuse. We explored the use of these antibiotics in Spain and analyzed the frequency, characteristics and prevention of CPE outbreaks. Future antibiotic stewardship programs along with specific preventive measures in hospitalized patients must be reinforced and updated in Spain. Full article
(This article belongs to the Special Issue Antibiotics Use and Antimicrobial Resistance in Hospital)
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Open AccessBrief Report
Is the Antimicrobial Activity of Hydrolates Lower than That of Essential Oils?
Antibiotics 2021, 10(1), 88; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010088 - 18 Jan 2021
Cited by 1 | Viewed by 427
Abstract
Among the top five human infections requiring medical treatment is dermatitis. Treatment of bacterial and fungal skin infections is usually based on antibiotic therapy, which is often ineffective due to the involvement of antibiotic-resistant microbial strains. The aim of this study was to [...] Read more.
Among the top five human infections requiring medical treatment is dermatitis. Treatment of bacterial and fungal skin infections is usually based on antibiotic therapy, which is often ineffective due to the involvement of antibiotic-resistant microbial strains. The aim of this study was to compare the antimicrobial activity of essential oils (EOs) and hydrolates (Hys) extracted from six aromatic plants grown in Italy (Lavandula angustifolia, Lavandula intermedia, Origanum hirtum, Satureja montana, Monarda didyma, and Monarda fistulosa) towards fungal (Candida albicans, Candida parapsilosis, Candida glabrata and Candida tropicalis; Trichophyton soudanense, Trichophyton tonsurans, Trichophyton rubrum, Trichophyton violaceum and Microsporum canis) and bacterial strains (Staphylococcus aureus MRSA, Staphylococcus aureus MSSA, Streptococcus pyogenes, E. faecalis, Enterococcus faecalis VRE, and Enterococcus faecium) potentially pathogenic for human skin. The composition and antimicrobial activity of EOs and Hys were evaluated using the Gas-chromatography mass spectrometry and micro dilution-broth test, respectively. The volatiles’ conversion factors (CFs) were calculated to compare the activity of Hys with that of the corresponding EOs. Data show that, although the minimum inhibitory concentration values of EOs are lower than the corresponding Hys, the volatiles contained in Hys are more effective at inhibiting microbial growth because they are active at lower concentrations. Full article
(This article belongs to the Special Issue Chemical Composition and Biological Activities of Essential Oils)
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Open AccessArticle
Bistable Bacterial Growth Dynamics in the Presence of Antimicrobial Agents
Antibiotics 2021, 10(1), 87; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010087 - 18 Jan 2021
Viewed by 426
Abstract
The outcome of an antibiotic treatment on the growth capacity of bacteria is largely dependent on the initial population size (Inoculum Effect). We characterized and built a model of this effect in E. coli cultures using a large variety of antimicrobials, including conventional [...] Read more.
The outcome of an antibiotic treatment on the growth capacity of bacteria is largely dependent on the initial population size (Inoculum Effect). We characterized and built a model of this effect in E. coli cultures using a large variety of antimicrobials, including conventional antibiotics, and for the first time, cationic antimicrobial peptides (CAMPs). Our results show that all classes of antimicrobial drugs induce an inoculum effect, which, as we explain, implies that the dynamic is bistable: For a range of anti-microbial densities, a very small inoculum decays whereas a larger inoculum grows, and the threshold inoculum depends on the drug concentration. We characterized three distinct classes of drug-induced bistable growth dynamics and demonstrate that in rich medium, CAMPs correspond to the simplest class, bacteriostatic antibiotics to the second class, and all other traditional antibiotics to the third, more complex class. These findings provide a unifying universal framework for describing the dynamics of the inoculum effect induced by antimicrobials with inherently different killing mechanisms. Full article
(This article belongs to the Section Antimicrobial Peptides)
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Open AccessArticle
Facile In-Situ Fabrication of a Ternary ZnO/TiO2/Ag Nanocomposite for Enhanced Bactericidal and Biocompatibility Properties
Antibiotics 2021, 10(1), 86; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010086 - 18 Jan 2021
Viewed by 412
Abstract
This paper presents for the first time a successful fabrication of ternary ZnO/TiO2/Ag nanocomposites consisting of zinc oxide (ZnO), titania (TiO2) and silver (Ag) nanoparticles (NPs) synthesised using Morinda citrifolia fruit (MCF) extract. ZnONPs were synthesised using the co-precipitation [...] Read more.
This paper presents for the first time a successful fabrication of ternary ZnO/TiO2/Ag nanocomposites consisting of zinc oxide (ZnO), titania (TiO2) and silver (Ag) nanoparticles (NPs) synthesised using Morinda citrifolia fruit (MCF) extract. ZnONPs were synthesised using the co-precipitation method, and TiO2 and Ag were introduced into the precursor solutions under microwave irradiation to obtain ZnO/TiO2/Ag nanocomposites (NCs). This material demonstrated enhanced bactericidal effect towards bacterial pathogens compared to that of the binary TiO2/Ag, Ag and TiO2 alone. In vitro cytotoxicity results of the as-synthesised ZnO/TiO2/AgNCs on RAW 264.7 macrophages and A549 cell lines revealed a negative role in cytotoxicity, but contributed astoundingly towards antimicrobials as compared of Ag alone and binary Ag/TiO2. This study shows that the resultant ternary metal/bi-semiconductor nanocomposites may provide a therapeutic strategy for the eradication of bacterial pathogens without affecting the healthy mammalian cells. Full article
(This article belongs to the Special Issue Discovery and Functional Evaluation of Antimicrobials)
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Open AccessArticle
Grapefruit Seed Extract as a Natural Derived Antibacterial Substance against Multidrug-Resistant Bacteria
Antibiotics 2021, 10(1), 85; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010085 - 18 Jan 2021
Viewed by 521
Abstract
Multidrug-resistant (MDR) bacteria are increasing due to the abuse and misuse of antibiotics, and nosocomial infections by MDR bacteria are also increasing. The aim of this study was to identify new substances that can target MDR bacteria among 12 plant extracts that are [...] Read more.
Multidrug-resistant (MDR) bacteria are increasing due to the abuse and misuse of antibiotics, and nosocomial infections by MDR bacteria are also increasing. The aim of this study was to identify new substances that can target MDR bacteria among 12 plant extracts that are known to have antibacterial effects. The experiments were performed by the disk diffusion test and microdilution minimum inhibitory concentration (MIC) test, as described by the Clinical and Laboratory Standards Institute (CLSI). By screening against methicillin-sensitive Staphylococcus aureus (MSSA), grapefruit seed extract (GSE) was selected from 12 plant extracts for subsequent experiments. GSE showed antibacterial effects against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) in the disk diffusion test. Even at the lowest concentration, GSE showed antibacterial activity in the microdilution MIC test. As a result, we can conclude that GSE is a naturally derived antibacterial substance that exhibits a favorable antibacterial effect even at a very low concentration, so it is a good candidate for a natural substance that can be used to prevent or reduce nosocomial infections as coating for materials used in medical contexts or by mixing a small amount with other materials. Full article
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Open AccessReview
Clavulanic Acid Production by Streptomyces clavuligerus: Insights from Systems Biology, Strain Engineering, and Downstream Processing
Antibiotics 2021, 10(1), 84; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010084 - 18 Jan 2021
Viewed by 657
Abstract
Clavulanic acid (CA) is an irreversible β-lactamase enzyme inhibitor with a weak antibacterial activity produced by Streptomyces clavuligerus (S. clavuligerus). CA is typically co-formulated with broad-spectrum β‑lactam antibiotics such as amoxicillin, conferring them high potential to treat diseases caused by bacteria [...] Read more.
Clavulanic acid (CA) is an irreversible β-lactamase enzyme inhibitor with a weak antibacterial activity produced by Streptomyces clavuligerus (S. clavuligerus). CA is typically co-formulated with broad-spectrum β‑lactam antibiotics such as amoxicillin, conferring them high potential to treat diseases caused by bacteria that possess β‑lactam resistance. The clinical importance of CA and the complexity of the production process motivate improvements from an interdisciplinary standpoint by integrating metabolic engineering strategies and knowledge on metabolic and regulatory events through systems biology and multi-omics approaches. In the large-scale bioprocessing, optimization of culture conditions, bioreactor design, agitation regime, as well as advances in CA separation and purification are required to improve the cost structure associated to CA production. This review presents the recent insights in CA production by S. clavuligerus, emphasizing on systems biology approaches, strain engineering, and downstream processing. Full article
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Open AccessArticle
A Qualitative Investigation of the Acceptability and Feasibility of a Urinary Tract Infection Patient Information Leaflet for Older Adults and Their Carers
Antibiotics 2021, 10(1), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010083 - 16 Jan 2021
Viewed by 465
Abstract
Urinary tract infections (UTIs) can be life threatening in older adults. The aim of this study was to primarily understand the acceptability and feasibility of using a UTI leaflet for older adults in care homes and the community. Qualitative interviews and focus groups [...] Read more.
Urinary tract infections (UTIs) can be life threatening in older adults. The aim of this study was to primarily understand the acceptability and feasibility of using a UTI leaflet for older adults in care homes and the community. Qualitative interviews and focus groups informed by the Theoretical Domains Framework were conducted in 2019 with 93 participants from two English areas where a UTI leaflet for older adults had been introduced to improve self-care advice. Discussions were conducted with care staff (carers and nurses), older adults, general practice staff (GPs, nurses and health care assistants), and other relevant stakeholders and covered experiences of using the leaflet; its implementation; and barriers and facilitators to use. Participants deemed the leaflet an acceptable tool. Clinicians and care staff believed that having information in writing would reinforce their messages to older adults. Care staff reported that some older adults may find the information overwhelming. Where implemented, care staff used the leaflet as an educational guide. Clinicians requested the leaflet in electronic and paper formats to suit preferences. Implementation barriers included lack of awareness of the leaflet, lack of staffing and resource, and weak working relationships between care homes and general practices. It is recommended that regional strategies must include plans for dissemination to care homes, training, promotion and easy access to the leaflet. Improvements to the leaflet consisted of inclusion of antibiotic course length, D-mannose, atrophic vaginitis and replacement of less alarmist terminology such as ‘life threatening’. Full article
(This article belongs to the Special Issue Antimicrobial Prescribing and Stewardship)
Open AccessArticle
Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus
Antibiotics 2021, 10(1), 82; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010082 - 16 Jan 2021
Viewed by 573
Abstract
Resveratrol has been extensively studied due to its potential health benefits in multiple diseases, for example, cancer, obesity and cardiovascular diseases. Besides these properties, resveratrol displays inhibitory activity against a wide range of bacterial species; however, the cellular effects of resveratrol in bacteria [...] Read more.
Resveratrol has been extensively studied due to its potential health benefits in multiple diseases, for example, cancer, obesity and cardiovascular diseases. Besides these properties, resveratrol displays inhibitory activity against a wide range of bacterial species; however, the cellular effects of resveratrol in bacteria remain incompletely understood, especially in the human pathogen, Staphylococcus aureus. In this study, we aimed to identify intrinsic resistance genes that aid S. aureus in tolerating the activity of resveratrol. We screened the Nebraska Transposon Mutant Library, consisting of 1920 mutants with inactivation of non-essential genes in S. aureus JE2, for increased susceptibly to resveratrol. On agar plates containing 0.5× the minimum inhibitory concentration (MIC), 17 transposon mutants failed to grow. Of these, four mutants showed a two-fold reduction in MIC, being the clpP protease mutant and three mutants with deficiencies in the electron transport chain (menD, hemB, aroC). The remaining 13 mutants did not show a reduction in MIC, but were confirmed by spot-assays to have increased susceptibility to resveratrol. Several genes were associated with DNA damage repair (recJ, xerC and xseA). Treatment of S. aureus JE2 with sub-inhibitory concentrations of resveratrol did not affect the expression of recJ, xerC and xseA, but increased expression of the SOS–stress response genes lexA and recA, suggesting that resveratrol interferes with DNA integrity in S. aureus. Expression of error-prone DNA polymerases are part of the SOS–stress response and we could show that sub-inhibitory concentrations of resveratrol increased overall mutation frequency as measured by formation of rifampicin resistant mutants. Our data show that DNA repair systems are important determinants aiding S. aureus to overcome the inhibitory activity of resveratrol. Activation of the SOS response by resveratrol could potentially facilitate the development of resistance towards conventional antibiotics in S. aureus. Full article
(This article belongs to the Special Issue Solutions to Antimicrobial Resistance)
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Open AccessArticle
Back to Nature: Combating Candida albicans Biofilm, Phospholipase and Hemolysin Using Plant Essential Oils
Antibiotics 2021, 10(1), 81; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010081 - 15 Jan 2021
Viewed by 419
Abstract
Candida albicans is the causative agent of fatal systemic candidiasis. Due to limitations of antifungals, new drugs are needed. The anti-virulence effect of plant essential oils (EOs) was evaluated against clinical C. albicans isolates including cinnamon, clove, jasmine and rosemary oils. Biofilm, phospholipase [...] Read more.
Candida albicans is the causative agent of fatal systemic candidiasis. Due to limitations of antifungals, new drugs are needed. The anti-virulence effect of plant essential oils (EOs) was evaluated against clinical C. albicans isolates including cinnamon, clove, jasmine and rosemary oils. Biofilm, phospholipase and hemolysin were assessed phenotypically. EOs were evaluated for their anti-virulence activity using phenotypic methods as well as scanning electron microscopy (SEM) and atomic force microscopy (AFM). Among the C. albicans isolates, biofilm, phospholipase and hemolysins were detected in 40.4, 86.5 and 78.8% of isolates, respectively. Jasmine oil showed the highest anti-biofilm activity followed by cinnamon, clove and rosemary oils. SEM and AFM analysis showed reduced adherence and roughness in the presence of EOs. For phospholipase, rosemary oil was the most inhibitory, followed by jasmine, cinnamon and clove oils, and for hemolysins, cinnamon had the highest inhibition followed by jasmine, rosemary and clove oils. A molecular docking study revealed major EO constituents as promising inhibitors of the Als3 adhesive protein, with the highest binding for eugenol, followed by 1,8-cineole, 2-phenylthiolane and cinnamaldehyde. In conclusion, EOs have a promising inhibitory impact on Candida biofilm, phospholipase and hemolysin production, hence EOs could be used as potential antifungals that impact virulence factors. Full article
(This article belongs to the Special Issue Antibacterial and Antibiofilm Activity of Plant Extracts)
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Open AccessArticle
Synergistic Effect of Abietic Acid with Oxacillin against Methicillin-Resistant Staphylococcus pseudintermedius
Antibiotics 2021, 10(1), 80; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010080 - 15 Jan 2021
Viewed by 392
Abstract
Resin acids are valued in traditional medicine for their antiseptic properties. Among these, abietic acid has been reported to be active against methicillin-resistant Staphylococcus aureus (MRSA) strains. In veterinary healthcare, the methicillin-resistant Staphylococcus pseudintermedius (MRSP) strain is an important reservoir of antibiotic resistance [...] Read more.
Resin acids are valued in traditional medicine for their antiseptic properties. Among these, abietic acid has been reported to be active against methicillin-resistant Staphylococcus aureus (MRSA) strains. In veterinary healthcare, the methicillin-resistant Staphylococcus pseudintermedius (MRSP) strain is an important reservoir of antibiotic resistance genes including mecA. The incidence of MRSP has been increasing, and treatment options in veterinary medicine are partial. Here, we investigated the antimicrobial and antibiofilm properties of abietic acid against three MRSP and two methicillin-susceptible Staphylococcus pseudintermedius (MSSP) strains, isolated from diseased pet animals and human wound samples. Abietic acid showed a significant minimal inhibitory concentration (MIC) value ranging from 32 to 64 μg/mL (MRSPs) and 8 μg/mL (MSSP). By checkerboard method we demonstrated that abietic acid increased oxacillin susceptibility of MRSP strains, thus showing a synergistic interaction with oxacillin. Abietic acid was also able to contrast the vitality of treated MSSP and MRSP1 biofilms at 20 μg/mL and 40 μg/mL, respectively. Finally, the compound moderately reduced mecA, mecR1 and mec1 gene expression. In conclusion, the results here reported demonstrate the antimicrobial activity of abietic acid against MRSP and support the use of this compound as a potential therapeutic agent to be used in combinatorial antibiotic therapy. Full article
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Open AccessArticle
Ceftolozane-Tazobactam Combination Therapy Compared to Ceftolozane-Tazobactam Monotherapy for the Treatment of Severe Infections: A Systematic Review and Meta-Analysis
Antibiotics 2021, 10(1), 79; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010079 - 15 Jan 2021
Viewed by 535
Abstract
Ceftolozane-tazobactam (C/T) is a combination of an advanced-generation cephalosporin (ceftolozane) with a β-lactamase inhibitor (tazobactam). It is approved for the treatment of complicated urinary-tract/intra-abdominal infections and hospital-acquired/ventilator-associated pneumonia. This systematic review and meta-analysis (registered prospectively on PROSPERO, no. CRD42019134099, on 20 January 2020) [...] Read more.
Ceftolozane-tazobactam (C/T) is a combination of an advanced-generation cephalosporin (ceftolozane) with a β-lactamase inhibitor (tazobactam). It is approved for the treatment of complicated urinary-tract/intra-abdominal infections and hospital-acquired/ventilator-associated pneumonia. This systematic review and meta-analysis (registered prospectively on PROSPERO, no. CRD42019134099, on 20 January 2020) aimed to evaluate the effectiveness of C/T combination therapy compared to C/T monotherapy for the treatment of severe infections and to describe the prevalence of microorganisms in the included studies. We retrieved literature from PubMed, EMBASE, and CENTRAL, until 26 November 2020. Eligible studies were both randomised trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was all-cause mortality; secondary outcomes were (i) clinical improvement and (ii) microbiological cure. Eight nonrandomised studies were included in the qualitative synthesis: Seven retrospective cohort studies and one case-control study. The meta-analysis of the four studies evaluating all-cause mortality (in total 148 patients: 87 patients treated with C/T alone and 61 patients treated with C/T combination therapy) showed a significant reduction of mortality in patients receiving C/T combination therapy, OR: 0.31, 95% CI: 0.10–0.97, p = 0.045. Conversely, the meta-analysis of the studies evaluating clinical improvement and microbiological cure showed no differences in C/T combination therapy compared to C/T monotherapy. The most consistent data come from the analysis of the clinical improvement, n = 391 patients, OR: 0.97, 95% CI: 0.54–1.74, p = 0.909. In 238 of the 391 patients included (60.8%), C/T was used for the treatment of infections caused by Pseudomonas aeruginosa. Full article
(This article belongs to the Special Issue Spread of Multidrug-Resistant Microorganisms )
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Open AccessArticle
Bacteriophage Cocktail-Mediated Inhibition of Pseudomonas aeruginosa Biofilm on Endotracheal Tube Surface
Antibiotics 2021, 10(1), 78; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010078 - 15 Jan 2021
Viewed by 406
Abstract
Although different strategies to control biofilm formation on endotracheal tubes have been proposed, there are scarce scientific data on applying phages for both removing and preventing Pseudomonas aeruginosa biofilms on the device surface. Here, the anti-biofilm capacity of five bacteriophages was evaluated by [...] Read more.
Although different strategies to control biofilm formation on endotracheal tubes have been proposed, there are scarce scientific data on applying phages for both removing and preventing Pseudomonas aeruginosa biofilms on the device surface. Here, the anti-biofilm capacity of five bacteriophages was evaluated by a high content screening assay. We observed that biofilms were significantly reduced after phage treatment, especially in multidrug-resistant strains. Considering the anti-biofilm screens, two phages were selected as cocktail components, and the cocktail’s ability to prevent colonization of the endotracheal tube surface was tested in a dynamic biofilm model. Phage-coated tubes were challenged with different P. aeruginosa strains. The biofilm growth was monitored from 24 to 168 h by colony forming unit counting, metabolic activity assessment, and biofilm morphology observation. The phage cocktail promoted differences of bacterial colonization; nonetheless, the action was strain dependent. Phage cocktail coating did not promote substantial changes in metabolic activity. Scanning electron microscopy revealed a higher concentration of biofilm cells in control, while tower-like structures could be observed on phage cocktail-coated tubes. These results demonstrate that with the development of new coating strategies, phage therapy has potential in controlling the endotracheal tube-associated biofilm. Full article
(This article belongs to the Special Issue New Insights on Biofilm Antimicrobial Strategies)
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Open AccessArticle
Valganciclovir—Ganciclovir Use and Systematic Therapeutic Drug Monitoring. An Invitation to Antiviral Stewardship
Antibiotics 2021, 10(1), 77; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010077 - 15 Jan 2021
Viewed by 486
Abstract
Valganciclovir (VGCV) and ganciclovir (GCV) doses must be adjusted according to indication, renal function and weight. No specific therapeutic exposure values have been established. We aimed to evaluate the adequacy of VGCV/GCV doses, to assess the interpatient variability in GCV serum levels, to [...] Read more.
Valganciclovir (VGCV) and ganciclovir (GCV) doses must be adjusted according to indication, renal function and weight. No specific therapeutic exposure values have been established. We aimed to evaluate the adequacy of VGCV/GCV doses, to assess the interpatient variability in GCV serum levels, to identify predictive factors for this variability and to assess the clinical impact. This is a prospective study at a tertiary institution including hospitalized patients receiving VGCV/GCV prophylaxis or treatment. Adequacy of the antiviral dose was defined according to cytomegalovirus guidelines. Serum levels were determined using High-Performance Liquid Chromatography. Blood samples were drawn at least 3 days after antiviral initiation. Outcome was considered favorable if there was no evidence of cytomegalovirus infection during prophylaxis or when a clinical and microbiological resolution was attained within 21 days of treatment and no need for drug discontinuation due to toxicity. Seventy consecutive patients [74.3% male/median age: 59.2 years] were included. VGCV was used in 25 patients (35.7%) and GCV in 45 (64.3%). VGCV/GCV initial dosage was deemed adequate in 47/70 cases (67.1%), lower than recommended in 7/70 (10%) and higher in 16/70 (22.9%). Large inter-individual variability of serum levels was observed, with median trough levels of 2.3 mg/L and median peak levels of 7.8 mg/L. Inadequate dosing of VGCV/GCV and peak levels lower than 8.37 or greater than 11.86 mg/L were related to poor outcome. Further studies must be performed to confirm these results and to conclusively establish if VGCV/GCV therapeutic drug monitoring could be useful to improve outcomes in specific clinical situations. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessArticle
Mortality of Pandrug-Resistant Klebsiella pneumoniae Bloodstream Infections in Critically Ill Patients: A Retrospective Cohort of 115 Episodes
Antibiotics 2021, 10(1), 76; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010076 - 15 Jan 2021
Viewed by 445
Abstract
Background: The increased frequency of bacteraemias caused by pandrug-resistant Klebsiella pneumoniae (PDR-Kp) has significant implications. The aim of the present study was to identify predictors associated with mortality of PDR-Kp bacteraemias. Methods: Patients with monomicrobial bacteraemia due to PDR-Kp were included. K. pneumoniae [...] Read more.
Background: The increased frequency of bacteraemias caused by pandrug-resistant Klebsiella pneumoniae (PDR-Kp) has significant implications. The aim of the present study was to identify predictors associated with mortality of PDR-Kp bacteraemias. Methods: Patients with monomicrobial bacteraemia due to PDR-Kp were included. K. pneumoniae was considered PDR if it showed resistance to all available groups of antibiotics. Primary outcome was 30-day mortality. Minimum inhibitory concentrations (MICs) of meropenem, tigecycline, fosfomycin, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. blaKPC, blaVIM, blaNDM, and blaOXA genes were detected by PCR. Results: Among 115 PDR-Kp bacteraemias, the majority of infections were primary bacteraemias (53; 46.1%), followed by catheter-related (35; 30.4%). All isolates were resistant to tested antimicrobials. blaKPC was the most prevalent carbapenemase gene (98 isolates; 85.2%). Thirty-day mortality was 39.1%; among 51 patients with septic shock, 30-day mortality was 54.9%. Multivariate analysis identified the development of septic shock, Charlson comorbidity index, and bacteraemia other than primary or catheter-related as independent predictors of mortality, while a combination of at least three antimicrobials was identified as an independent predictor of survival. Conclusions: Mortality of PDR-Kp bloodstream infections was high. Administration of at least three antimicrobials might be beneficial for infections in critically ill patients caused by such pathogens. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Open AccessArticle
Prevalence and Characterization of Coagulase Positive Staphylococci from Food Products and Human Specimens in Egypt
Antibiotics 2021, 10(1), 75; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010075 - 14 Jan 2021
Viewed by 675
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) strains have veterinary and public health importance as they are responsible for a wide range of difficult to treat infections and food poisoning. Two hundred samples (50 samples each of minced meat, beef luncheon, Karish cheese, and human samples [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) strains have veterinary and public health importance as they are responsible for a wide range of difficult to treat infections and food poisoning. Two hundred samples (50 samples each of minced meat, beef luncheon, Karish cheese, and human samples (pus swab from open wounds)) were cultured, and MRSA strains were identified using disk diffusion tests and mecA gene-based PCR. A total of 35% (70/200) of the examined samples were confirmed as coagulase-positive S. aureus in minced meat (46%), beef luncheon (44%), Karish cheese (44%), and human samples (22%). The MRSA strains showed resistance to amoxicillin (91.4%), penicillin (97.1%), cefoxitin (85.7%), cephradine (82.9%), tetracycline (57.2%), and erythromycin (52.8%). More than half of the tested S. aureus isolates harbored the mecA gene. The sequence analysis of the mecA gene from the minced meat, Karish cheese, and human samples revealed high genetic similarities between the S. aureus isolates from these sources. In conclusion, our findings indicate a risk for the transmission of the mecA gene of S. aureus across the food chain between humans and animal food products. Further studies should focus on finding additional epidemiological aspects of the MRSA strains in food chain. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: From Farm to Fork)
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Open AccessArticle
Antimicrobial Resistance of Non-O157 Shiga Toxin-Producing Escherichia coli Isolated from Humans and Domestic Animals
Antibiotics 2021, 10(1), 74; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010074 - 14 Jan 2021
Viewed by 420
Abstract
Non-O157 Shiga toxin-producing Escherichia coli (STEC) is an important pathogen that can cause zoonotic diseases. To investigate the antimicrobial resistance of STEC in China, non-O157 STEC isolates, recovered from domestic animals and humans from 12 provinces, were analyzed using antimicrobial susceptibility testing and [...] Read more.
Non-O157 Shiga toxin-producing Escherichia coli (STEC) is an important pathogen that can cause zoonotic diseases. To investigate the antimicrobial resistance of STEC in China, non-O157 STEC isolates, recovered from domestic animals and humans from 12 provinces, were analyzed using antimicrobial susceptibility testing and whole genome characterization. Out of the 298 isolates tested, 115 strains showed resistance to at least one antimicrobial and 85 strains showed multidrug resistance. The highest resistance rate was to tetracycline (32.6%), followed by nalidixic acid (25.2%) and chloramphenicol and azithromycin (both 18.8%). However, imipenem and meropenem were effective against all isolates. Antimicrobial resistance patterns varied among strains from different sources. Strains from pig, sheep, humans, and cattle showed resistance rates of 100.0%, 46.9%, 30.3%, and 6.3% to one or more antimicrobials, respectively. Forty-three genes related to 11 antimicrobial classes were identified among these strains. The colistin-resistance gene mcr was only carried by strains from pigs. A new fosfomycin-resistant gene, fosA7, was detected in strains from humans, cattle, and sheep. Whole genome phylogenetic analysis showed that strains from the four sources were genetically diverse and scattered throughout the phylogenetic tree; however, some strains from the same source had a tendency to cluster closely. These results provide a reference to monitor the emergence and spread of multidrug resistant STEC strains among animals and humans. Furthermore, with a better understanding of antimicrobial genotypes and phenotypes among the diverse STEC strains obtained, this study could guide the administration of antimicrobial drugs in STEC infections when necessary. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessArticle
Defining the Scope of Antimicrobial Stewardship Interventions on the Prescription Quality of Antibiotics for Surgical Intra-Abdominal Infections
Antibiotics 2021, 10(1), 73; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010073 - 14 Jan 2021
Viewed by 377
Abstract
Background: The aim of this study was to assess the impact of antimicrobial stewardship interventions on surgical antibiotic prescription behavior in the management of non-elective surgical intra-abdominal infections, focusing on postoperative antibiotic use, including the appropriateness of indications. Methods: A single-center quality improvement [...] Read more.
Background: The aim of this study was to assess the impact of antimicrobial stewardship interventions on surgical antibiotic prescription behavior in the management of non-elective surgical intra-abdominal infections, focusing on postoperative antibiotic use, including the appropriateness of indications. Methods: A single-center quality improvement study with retrospective evaluation of the impact of antimicrobial stewardship measures on optimizing antibacterial use in intra-abdominal infections requiring emergency surgery was performed. The study was conducted in a tertiary hospital in Germany from January 1, 2016, to January 30, 2020, three years after putting a set of antimicrobial stewardship standards into effect. Results: 767 patients were analyzed (n = 495 in 2016 and 2017, the baseline period; n = 272 in 2018, the antimicrobial stewardship period). The total days of therapy per 100 patient days declined from 47.0 to 42.2 days (p = 0.035). The rate of patients receiving postoperative therapy decreased from 56.8% to 45.2% (p = 0.002), comparing both periods. There was a significant decline in the rate of inappropriate indications (17.4% to 8.1 %, p = 0.015) as well as a significant change from broad-spectrum to narrow-spectrum antibiotic use (28.8% to 6.5%, p ≤ 0.001) for postoperative therapy. The significant decline in antibiotic use did not affect either clinical outcomes or the rate of postoperative wound complications. Conclusions: Postoperative antibiotic use for intra-abdominal infections could be significantly reduced by antimicrobial stewardship interventions. The identification of inappropriate indications remains a key target for antimicrobial stewardship programs. Full article
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Open AccessArticle
A Molecule of the Viridomycin Family Originating from a Streptomyces griseus-Related Strain Has the Ability to Solubilize Rock Phosphate and to Inhibit Microbial Growth
Antibiotics 2021, 10(1), 72; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010072 - 14 Jan 2021
Viewed by 413
Abstract
Some soil-borne microorganisms are known to have the ability to solubilize insoluble rock phosphate and this process often involves the excretion of organic acids. In this issue, we describe the characterization of a novel solubilizing mechanism used by a Streptomyces strain related to [...] Read more.
Some soil-borne microorganisms are known to have the ability to solubilize insoluble rock phosphate and this process often involves the excretion of organic acids. In this issue, we describe the characterization of a novel solubilizing mechanism used by a Streptomyces strain related to Streptomyces griseus isolated from Moroccan phosphate mines. This process involves the excretion of a compound belonging to the viridomycin family that was shown to play a major role in the rock phosphate bio weathering process. We propose that the chelation of the positively charged counter ions of phosphate constitutive of rock phosphate by this molecule leads to the destabilization of the structure of rock phosphate. This would result in the solubilization of the negatively charged phosphates, making them available for plant nutrition. Furthermore, this compound was shown to inhibit growth of fungi and Gram positive bacteria, and this antibiotic activity might be due to its strong ability to chelate iron, a metallic ion indispensable for microbial growth. Considering its interesting properties, this metabolite or strains producing it could contribute to the development of sustainable agriculture acting as a novel type of slow release bio-phosphate fertilizer that has also the interesting ability to limit the growth of some common plant pathogens. Full article
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Open AccessArticle
Clinical Presentation and Incidence of Anaerobic Bacteria in Surgically Treated Biliary Tract Infections and Cholecystitis
Antibiotics 2021, 10(1), 71; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010071 - 13 Jan 2021
Cited by 1 | Viewed by 340
Abstract
(1) Background: Cholecystitis and cholangitis are among the most common diseases treated by general surgery. Gallstones lead to inflammation and bacterial infection of the biliary tract. Biliary infections can lead to live threatening bacteremia and liver abscesses. The true role of anaerobes remains [...] Read more.
(1) Background: Cholecystitis and cholangitis are among the most common diseases treated by general surgery. Gallstones lead to inflammation and bacterial infection of the biliary tract. Biliary infections can lead to live threatening bacteremia and liver abscesses. The true role of anaerobes remains unclear. (2) Methods: We retrospectively analyzed bacterial cultures from biliary samples obtained from bile ducts and gallbladders at our tertiary care center. Patient characteristics and clinical outcomes were analyzed. (3) Results: In our database of 1719 patients, 365 patients had microbial testing, of which 42 grew anaerobic bacteria. Anaerobes were more frequently cultured in patients with hepatic abscesses and gallbladder perforation. These patients were older and had more comorbidities than the control group. The overall outcomes of all patients were favorable and the resistance rate to commonly used antibiotics remained low. (4) Conclusions: Anaerobes in biliary tract infections appear to be underdiagnosed and more prevalent in the elderly with advanced disease. Due to low antibiotic resistance, the combination of source control and adjunct anti-infective treatment leads to favorable outcomes. Full article
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Open AccessEditorial
Natural Products and Their Derivatives with Antibacterial, Antioxidant and Anticancer Activities
Antibiotics 2021, 10(1), 70; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010070 - 13 Jan 2021
Viewed by 386
Abstract
Natural products and their derivatives have been commonly used in our daily life, as they play important roles in boosting immune systems and fighting diseases [...] Full article
Open AccessReview
Antimicrobial Resistance in Escherichia coli Strains Isolated from Humans and Pet Animals
Antibiotics 2021, 10(1), 69; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010069 - 13 Jan 2021
Viewed by 682
Abstract
Throughout scientific literature, we can find evidence that antimicrobial resistance has become a big problem in the recent years on a global scale. Public healthcare systems all over the world are faced with a great challenge in this respect. Obviously, there are many [...] Read more.
Throughout scientific literature, we can find evidence that antimicrobial resistance has become a big problem in the recent years on a global scale. Public healthcare systems all over the world are faced with a great challenge in this respect. Obviously, there are many bacteria that can cause infections in humans and animals alike, but somehow it seems that the greatest threat nowadays comes from the Enterobacteriaceae members, especially Escherichia coli. Namely, we are witnesses to the fact that the systems that these bacteria developed to fight off antibiotics are the strongest and most diverse in Enterobacteriaceae. Our great advantage is in understanding the systems that bacteria developed to fight off antibiotics, so these can help us understand the connection between these microorganisms and the occurrence of antibiotic-resistance both in humans and their pets. Furthermore, unfavorable conditions related to the ease of E. coli transmission via the fecal–oral route among humans, environmental sources, and animals only add to the problem. For all the above stated reasons, it is evident that the epidemiology of E. coli strains and resistance mechanisms they have developed over time are extremely significant topics and all scientific findings in this area will be of vital importance in the fight against infections caused by these bacteria. Full article
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Open AccessReview
Insects, Rodents, and Pets as Reservoirs, Vectors, and Sentinels of Antimicrobial Resistance
Antibiotics 2021, 10(1), 68; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010068 - 12 Jan 2021
Viewed by 695
Abstract
This paper reviews the occurrence of antimicrobial resistance (AMR) in insects, rodents, and pets. Insects (e.g., houseflies, cockroaches), rodents (rats, mice), and pets (dogs, cats) act as reservoirs of AMR for first-line and last-resort antimicrobial agents. AMR proliferates in insects, rodents, and pets, [...] Read more.
This paper reviews the occurrence of antimicrobial resistance (AMR) in insects, rodents, and pets. Insects (e.g., houseflies, cockroaches), rodents (rats, mice), and pets (dogs, cats) act as reservoirs of AMR for first-line and last-resort antimicrobial agents. AMR proliferates in insects, rodents, and pets, and their skin and gut systems. Subsequently, insects, rodents, and pets act as vectors that disseminate AMR to humans via direct contact, human food contamination, and horizontal gene transfer. Thus, insects, rodents, and pets might act as sentinels or bioindicators of AMR. Human health risks are discussed, including those unique to low-income countries. Current evidence on human health risks is largely inferential and based on qualitative data, but comprehensive statistics based on quantitative microbial risk assessment (QMRA) are still lacking. Hence, tracing human health risks of AMR to insects, rodents, and pets, remains a challenge. To safeguard human health, mitigation measures are proposed, based on the one-health approach. Future research should include human health risk analysis using QMRA, and the application of in-silico techniques, genomics, network analysis, and ’big data’ analytical tools to understand the role of household insects, rodents, and pets in the persistence, circulation, and health risks of AMR. Full article
(This article belongs to the Special Issue Antimicrobial Resistance and the Environment: One Health Approach)
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Open AccessArticle
Antibiotic Prescribing Practices in Endodontic Infections: A Survey of Dentists in Serbia
Antibiotics 2021, 10(1), 67; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010067 - 12 Jan 2021
Viewed by 348
Abstract
The study goal was to provide an overview of antibiotic prescribing practices of Serbian dentists when treating endodontic infections and to disseminate the current ESE (European Society of Endodontology) recommendations to the study participants. A link to an online questionnaire was sent to [...] Read more.
The study goal was to provide an overview of antibiotic prescribing practices of Serbian dentists when treating endodontic infections and to disseminate the current ESE (European Society of Endodontology) recommendations to the study participants. A link to an online questionnaire was sent to 628 Serbian dentists whose email addresses were publicly available on the Internet, 158 of whom responded to the survey, resulting in a 25.16% response rate. The significance of possible associations was assessed via the Chi-squared test and Cramer’s V measure of association, with p < 0.05 considered as statistically significant. According to the study findings, 55.7% of respondents prescribed a 5-day antibiotic course. Moreover, Amoxicillin 500 mg was the first-choice antibiotic for 55.1% of the respondents, followed by Clindamycin 600 mg (18.4%). For patients allergic to penicillin, 61.4% of respondents prescribed Clindamycin. Statistically significant differences emerged only in relation to acute apical abscess with systemic involvement, whereby dentists aged 46–55 were least likely to prescribe antibiotics in these clinical situations (p = 0.04). Analyses further revealed that recommendations for safe antibiotic prescribing practices were not always followed, as in certain cases, patients were given antibiotics even when this was not indicated. These findings highlight the need for additional education on responsible antibiotic use to prevent bacterial resistance. Full article
(This article belongs to the Special Issue Antibiotic Use in the Communities)
Open AccessArticle
Understanding of Pharmacy Students towards Antibiotic Use, Antibiotic Resistance and Antibiotic Stewardship Programs: A Cross-Sectional Study from Punjab, Pakistan
Antibiotics 2021, 10(1), 66; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010066 - 12 Jan 2021
Viewed by 586
Abstract
Antibiotic resistance (ABR) is a significant issue for public health globally. An adequate understanding of ABR and the approaches used to tackle ABR, including antibiotic stewardship programs, are vital. This study aimed to get an insight into antibiotic use, ABR, and antibiotic stewardship [...] Read more.
Antibiotic resistance (ABR) is a significant issue for public health globally. An adequate understanding of ABR and the approaches used to tackle ABR, including antibiotic stewardship programs, are vital. This study aimed to get an insight into antibiotic use, ABR, and antibiotic stewardship programs among pharmacy students of Punjab, Pakistan. This multicenter study was undertaken among final (fifth) year undergraduate pharmacy students of 7 universities of Punjab, Pakistan. A paper-based self-administered questionnaire comprising 48-items was utilized for data collection. Descriptive and inferential statistics were employed for data analysis. This study included a total of 296 respondents with a response rate of 85.8%. Most of the students had an average understanding of antibiotic use (59.8%), ABR (42.6%), ABR mechanisms (48.0%), and factors of ABR (51.7%). Only 21.6% of students have heard about antibiotic stewardship programs. More than half of the students believed that educating and training healthcare professionals (53.4%) and medical students (57.8%) about the prescribing and judicial usage of antibiotics could reduce the ABR burden. The awareness of most of the pharmacy students about certain aspects of antibiotic use, ABR, and stewardship programs was suboptimal. Full article
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