Showing papers in "The Journal of Antibiotics in 2021"
TL;DR: In this paper, the authors provide a concise summary on the adaptability, virulence, and antibiotic resistance of Pseudomonas aeruginosa to a readership of basic scientists and clinicians.
Abstract: Pseudomonas aeruginosa is the most frequent cause of infection among non-fermenting Gram-negative bacteria, predominantly affecting immunocompromised patients, but its pathogenic role should not be disregarded in immunocompetent patients. These pathogens present a concerning therapeutic challenge to clinicians, both in community and in hospital settings, due to their increasing prevalence of resistance, and this may lead to prolonged therapy, sequelae, and excess mortality in the affected patient population. The resistance mechanisms of P. aeruginosa may be classified into intrinsic and acquired resistance mechanisms. These mechanisms lead to occurrence of resistant strains against important antibiotics—relevant in the treatment of P. aeruginosa infections—such as β-lactams, quinolones, aminoglycosides, and colistin. The occurrence of a specific resistotype of P. aeruginosa, namely the emergence of carbapenem-resistant but cephalosporin-susceptible (Car-R/Ceph-S) strains, has received substantial attention from clinical microbiologists and infection control specialists; nevertheless, the available literature on this topic is still scarce. The aim of this present review paper is to provide a concise summary on the adaptability, virulence, and antibiotic resistance of P. aeruginosa to a readership of basic scientists and clinicians.
105 citations
TL;DR: The use of metal oxide nanoparticles (IONPs) is one of the promising ways for overcoming antibiotic resistance in bacteria and fungi as discussed by the authors, however, the effectiveness of IONPs has not yet been evaluated.
Abstract: The use of metal oxide nanoparticles is one of the promising ways for overcoming antibiotic resistance in bacteria. Iron oxide nanoparticles (IONPs) have found wide applications in different fields of biomedicine. Several studies have suggested using the antimicrobial potential of IONPs. Iron is one of the key microelements and plays an important role in the function of living systems of different hierarchies. Iron abundance and its physiological functions bring into question the ability of iron compounds at the same concentrations, on the one hand, to inhibit the microbial growth and, on the other hand, to positively affect mammalian cells. At present, multiple studies have been published that show the antimicrobial effect of IONPs against Gram-negative and Gram-positive bacteria and fungi. Several studies have established that IONPs have a low toxicity to eukaryotic cells. It gives hope that IONPs can be considered potential antimicrobial agents of the new generation that combine antimicrobial action and high biocompatibility with the human body. This review is intended to inform readers about the available data on the antimicrobial properties of IONPs, a range of susceptible bacteria, mechanisms of the antibacterial action, dependence of the antibacterial action of IONPs on the method for synthesis, and the biocompatibility of IONPs with eukaryotic cells and tissues.
104 citations
TL;DR: Wang et al. as discussed by the authors addressed the pollution problems of antibiotics; in particular, the wide spread of antimicrobial resistance (AMR), which seriously affects animal and human health, food safety, ecosystems, and the sustainable future development of animal protein production.
Abstract: The demand for animal protein has increased considerably worldwide, especially in China, where large numbers of livestock and poultry are produced. Antibiotics have been widely applied to promote growth and prevent diseases. However, the overuse of antibiotics in animal feed has caused serious environmental and health risks, especially the wide spread of antimicrobial resistance (AMR), which seriously affects animal and human health, food safety, ecosystems, and the sustainable future development of animal protein production. Unfortunately, AMR has already become a worldwide challenge, so international cooperation is becoming more important for combatting it. China's efforts and determination to restrict antibiotic usage through law enforcement and effective management are of significance. In this review, we address the pollution problems of antibiotics; in particular, the AMR in water, soil, and plants caused by livestock and poultry manure in China. The negative impact of widespread and intensive use of antibiotics in livestock production is discussed. To reduce and mitigate AMR problems, we emphasize in this review the development of antibiotic substitutes for the era of antibiotic prohibition.
59 citations
TL;DR: In this paper, the synergy between endolysins and antibiotics is discussed, as well as the formulation of endolysin formulations for clinical trials involving endolySins, and the authors provide new insights into the synergy and synergy between the two drugs.
Abstract: Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.
57 citations
TL;DR: A review of antimicrobial resistance mechanisms in infectious bacteria can be found in this article, where the authors summarize the various antimicrobial mechanisms that are harbored within infectious bacteria and present suitable focuses for investigation to establish the means for their circumvention and to reestablish therapeutic effectiveness.
Abstract: Bacterial pathogens as causative agents of infection constitute an alarming concern in the public health sector. In particular, bacteria with resistance to multiple antimicrobial agents can confound chemotherapeutic efficacy towards infectious diseases. Multidrug-resistant bacteria harbor various molecular and cellular mechanisms for antimicrobial resistance. These antimicrobial resistance mechanisms include active antimicrobial efflux, reduced drug entry into cells of pathogens, enzymatic metabolism of antimicrobial agents to inactive products, biofilm formation, altered drug targets, and protection of antimicrobial targets. These microbial systems represent suitable focuses for investigation to establish the means for their circumvention and to reestablish therapeutic effectiveness. This review briefly summarizes the various antimicrobial resistance mechanisms that are harbored within infectious bacteria.
56 citations
TL;DR: In this article, a review of emerging contaminants (ECs) in leachate from landfills is presented, highlighting the need to develop a novel eco-friendly management strategy to combat these global issues.
Abstract: The disposal of municipal solid waste (MSW) directly at landfills or open dump areas, without segregation and treatment, is a significant concern due to its hazardous contents of antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs), and metal resistance genes (MGEs). The released leachate from landfills greatly effects the soil physicochemical, biological, and groundwater properties associated with agricultural activity and human health. The abundance of ARB, ARGs, and MGEs have been reported worldwide, including MSW landfill sites, animal husbandry, wastewater, groundwater, soil, and aerosol. This review elucidates the occurrence and abundance of ARB, ARGs, and MRGs, which are regarded as emerging contaminants (ECs). Recently, ECs have received global attention because of their prevalence in leachate as a substantial threat to environmental and public health, including an economic burden for developing nations. The present review exclusively discusses the demands to develop a novel eco-friendly management strategy to combat these global issues. This review also gives an intrinsic discussion about the insights of different aspects of environmental and public health concerns caused due to massive leachate generation, the abundance of antibiotics resistance (AR), and the effects of released leachate on the various environmental reservoirs and human health. Furthermore, the current review throws light on the source and fate of different ECs of landfill leachate and their possible impact on the nearby environments (groundwater, surface water, and soil) affecting human health. The present review strongly suggests the demand for future research focuses on the advancement of the removal efficiency of contaminants with the improvement of relevant landfill management to reduce the potential effects of disposable waste. We propose the necessity of the identification and monitoring of potential environmental and human health risks associated with landfill leachate contaminants.
52 citations
TL;DR: New compounds, including volatiles as well as nonvolatiles, are steadily being discovered from these ascomycetes, and polythetic taxonomy now allows for elucidation of the life cycle of the endophytes for the first time.
Abstract: The families Xylariaceae and Hypoxylaceae (Xylariales, Ascomycota) represent one of the most prolific lineages of secondary metabolite producers. Like many other fungal taxa, they exhibit their highest diversity in the tropics. The stromata as well as the mycelial cultures of these fungi (the latter of which are frequently being isolated as endophytes of seed plants) have given rise to the discovery of many unprecedented secondary metabolites. Some of those served as lead compounds for development of pharmaceuticals and agrochemicals. Recently, the endophytic Xylariales have also come in the focus of biological control, since some of their species show strong antagonistic effects against fungal and other pathogens. New compounds, including volatiles as well as nonvolatiles, are steadily being discovered from these ascomycetes, and polythetic taxonomy now allows for elucidation of the life cycle of the endophytes for the first time. Moreover, recently high-quality genome sequences of some strains have become available, which facilitates phylogenomic studies as well as the elucidation of the biosynthetic gene clusters (BGC) as a starting point for synthetic biotechnology approaches. In this review, we summarize recent findings, focusing on the publications of the past 3 years.
51 citations
TL;DR: In this article, a retrospective data collection and evaluation was conducted to include all the patients hospitalized for TB at INMI from 9 March to 31 August 2020 (lockdown period and three months thereafter).
Abstract: Background: The WHO advised that the impact of COVID-19 pandemic on TB services was estimated to be dramatic due to the disruption of TB services. Methods: A retrospective data collection and evaluation was conducted to include all the patients hospitalized for TB at INMI from 9 March to 31 August 2020 (lockdown period and three months thereafter). For the purpose of the study, data from patients hospitalized in the same period of 2019 were also collected. Results: In the period of March–August 2019, 201 patients were hospitalized with a diagnosis of TB, while in the same period of 2020, only 115 patients, with a case reduction of 43%. Patients with weight loss, acute respiratory failure, concurrent extrapulmonary TB, and higher Timika radiographic scores were significantly more frequently hospitalized during 2020 vs. 2019. The median patient delay was 75 days (IQR: 40–100) in 2020 compared to 30 days (IQR: 10–60) in 2019 (p < 0.01). Diagnostic delays in 2020 remain significant in the multiple logistic model (AOR = 6.93, 95%CI: 3.9–12.3). Conclusions: Our experience suggests that COVID-19 pandemic had an impact on TB patient care in terms of higher diagnostic delay, reduction in hospitalization, and a greater severity of clinical presentations.
50 citations
TL;DR: In this article, the combination of aztreonam and avibactam was used to treat metallo-β-lactamase (MBL)-producing bacteria.
Abstract: Infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales and Pseudomonas are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. However, since many MBL-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g., AmpC, ESBL), a robust β-lactamase inhibitor such as avibactam could be given as a partner drug. We performed a systematic review including 35 in vitro and 18 in vivo studies on the combination aztreonam + avibactam for infections sustained by MBL-producing Gram-negatives. In vitro data on 2209 Gram-negatives were available, showing the high antimicrobial activity of aztreonam (MIC ≤ 4 mg/L when combined with avibactam) in 80% of MBL-producing Enterobacterales, 85% of Stenotrophomonas and 6% of MBL-producing Pseudomonas. Clinical data were available for 94 patients: 83% of them had bloodstream infections. Clinical resolution within 30 days was reported in 80% of infected patients. Analyzing only patients with bloodstream infections (64 patients), death occurred in 19% of patients treated with aztreonam + ceftazidime/avibactam. The combination aztreonam + avibactam appears to be a promising option against MBL-producing bacteria (especially Enterobacterales, much less for Pseudomonas) while waiting for new antimicrobials.
49 citations
TL;DR: A review of different types of nanomaterials explored specifically for wound healing properties combined with infection control is presented in this paper, where the authors present an overview of various types of NM materials for wound wound dressing drug formulations and materials with combined antibacterial, antibiofilm and wound health properties.
Abstract: Wounds continue to be a serious medical concern due to their increasing incidence from injuries, surgery, burns and chronic diseases such as diabetes. Delays in the healing process are influenced by infectious microbes, especially when they are in the biofilm form, which leads to a persistent infection. Biofilms are well known for their increased antibiotic resistance. Therefore, the development of novel wound dressing drug formulations and materials with combined antibacterial, antibiofilm and wound healing properties are required. Nanomaterials (NM) have unique properties due to their size and very large surface area that leads to a wide range of applications. Several NMs have antimicrobial activity combined with wound regeneration features thus give them promising applicability to a variety of wound types. The idea of NM-based antibiotics has been around for a decade at least and there are many recent reviews of the use of nanomaterials as antimicrobials. However, far less attention has been given to exploring if these NMs actually improve wound healing outcomes. In this review, we present an overview of different types of nanomaterials explored specifically for wound healing properties combined with infection control.
49 citations
TL;DR: In this paper, the authors provide an overview of current knowledge of the stages of biofilm development and what difficulties may arise when trying to eradicate staphylococcal biofilms.
Abstract: Staphylococci, like Staphylococcus aureus and S epidermidis, are common colonizers of the human microbiota While being harmless in many cases, many virulence factors result in them being opportunistic pathogens and one of the major causes of hospital-acquired infections worldwide One of these virulence factors is the ability to form biofilms-three-dimensional communities of microorganisms embedded in an extracellular polymeric matrix (EPS) The EPS is composed of polysaccharides, proteins and extracellular DNA, and is finely regulated in response to environmental conditions This structured environment protects the embedded bacteria from the human immune system and decreases their susceptibility to antimicrobials, making infections caused by staphylococci particularly difficult to treat With the rise of antibiotic-resistant staphylococci, together with difficulty in removing biofilms, there is a great need for new treatment strategies The purpose of this review is to provide an overview of our current knowledge of the stages of biofilm development and what difficulties may arise when trying to eradicate staphylococcal biofilms Furthermore, we look into promising targets and therapeutic methods, including bacteriocins and phage-derived antibiofilm approaches
TL;DR: In this paper, the authors present a review of the chemical structures and the antibacterial activities and mechanisms of alkaloids and provide a certain theoretical basis and research ideas for the development of new antibacterial drugs.
Abstract: Alkaloids are nitrogen-containing heterocyclic compounds typically isolated from plants. They represent one of the most important types of natural products because of their large number and structural diversity and complexity. Based on their chemical core structures, alkaloids are classified as isoquinolines, quinolines, indoles, piperidine alkaloids, etc. In-depth analyses of alkaloids have revealed their antibacterial activities. To date, due to the widespread use of antibiotics, the problem of drug-resistant bacterial infections has been gradually increasing, which severely affects the clinical efficacy of antibacterial therapies and patient safety. Therefore, significant research efforts are focused on alkaloids because they represent a potentially new type of natural antibiotic with a wide antibacterial spectrum, rare adverse reactions, and a low tendency to produce drug resistance. Their main antibacterial mechanisms include inhibition of bacterial cell wall synthesis, change in cell membrane permeability, inhibition of bacterial metabolism, and inhibition of nucleic acid and protein synthesis. This article reviews recent reports about the chemical structures and the antibacterial activities and mechanisms of alkaloids. The purpose is to solve the problem of bacterial resistance and to provide a certain theoretical basis and research ideas for the development of new antibacterial drugs.
TL;DR: In this article, the authors performed a systematic review and meta-analysis to estimate the pooled occurrence of ventilator-associated pneumonia (VAP) among patients admitted to an intensive care unit with COVID-19 and mortality of those who developed VAP.
Abstract: The aim of this systematic review and meta-analysis was to estimate the pooled occurrence of ventilator-associated pneumonia (VAP) among patients admitted to an intensive care unit with COVID-19 and mortality of those who developed VAP. We performed a systematic search on PubMed, EMBASE and Web of Science from inception to 2nd March 2021 for nonrandomized studies specifically addressing VAP in adult patients with COVID-19 and reporting data on at least one primary outcome of interest. Random effect single-arm meta-analysis was performed for the occurrence of VAP and mortality (at the longest follow up) and ICU length of stay. Twenty studies were included in the systematic review and meta-analysis, for a total of 2611 patients with at least one episode of VAP. The pooled estimated occurrence of VAP was of 45.4% (95% C.I. 37.8-53.2%; 2611/5593 patients; I2 = 96%). The pooled estimated occurrence of mortality was 42.7% (95% C.I. 34-51.7%; 371/946 patients; I2 = 82%). The estimated summary estimated metric mean ICU LOS was 28.58 days (95% C.I. 21.4-35.8; I2 = 98%). Sensitivity analysis showed that patients with COVID-19 may have a higher risk of developing VAP than patients without COVID-19 (OR 3.24; 95% C.I. 2.2-4.7; P = 0.015; I2 = 67.7%; five studies with a comparison group).
TL;DR: In this paper, a pH-responsive hydrogel that can provide controlled, pH-triggered release of silver nanoparticles (AgNPs) was designed to sense the environmental pH and trigger the release of AgNPs when the pH changes from acidic to alkaline due to the presence of pathogenic bacteria in the wound.
Abstract: Persistent wound infections have been a therapeutic challenge for a long time. Current treatment approaches are mostly based on the delivery of antibiotics, but these are not effective for all infections. Here, we report the development of a sensitive pH-responsive hydrogel that can provide controlled, pH-triggered release of silver nanoparticles (AgNPs). This delivery system was designed to sense the environmental pH and trigger the release of AgNPs when the pH changes from acidic to alkaline, as occurs due to the presence of pathogenic bacteria in the wound. Our results show that the prepared hydrogel restricts the release of AgNPs at acidic pH (pH = 4) but substantially amplifies it at alkaline pH (pH = 7.4 and pH = 10). This indicates the potential use of the hydrogel for the on-demand release of Ag+ depending on the environmental pH. In vitro antibacterial studies demonstrated effective elimination of both Gram-negative and positive bacteria. Additionally, the effective antibacterial dose of Ag+ showed no toxicity towards mammalian skin cells. Collectively, this pH-responsive hydrogel presents potential as a promising new material for the treatment of infected wounds.
TL;DR: In this article, a review describes the developments in current cutting-edge methods and technologies, organized by key enabling research domains, towards fighting the looming antimicrobial resistance (AMR) menace by employing recent advances in AMR diagnostic tools.
Abstract: Antimicrobial resistance (AMR) is one of the most challenging threats in public health; thus, there is a growing demand for methods and technologies that enable rapid antimicrobial susceptibility testing (AST). The conventional methods and technologies addressing AMR diagnostics and AST employed in clinical microbiology are tedious, with high turnaround times (TAT), and are usually expensive. As a result, empirical antimicrobial therapies are prescribed leading to AMR spread, which in turn causes higher mortality rates and increased healthcare costs. This review describes the developments in current cutting-edge methods and technologies, organized by key enabling research domains, towards fighting the looming AMR menace by employing recent advances in AMR diagnostic tools. First, we summarize the conventional methods addressing AMR detection, surveillance, and AST. Thereafter, we examine more recent non-conventional methods and the advancements in each field, including whole genome sequencing (WGS), matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) spectrometry, Fourier transform infrared (FTIR) spectroscopy, and microfluidics technology. Following, we provide examples of commercially available diagnostic platforms for AST. Finally, perspectives on the implementation of emerging concepts towards developing paradigm-changing technologies and methodologies for AMR diagnostics are discussed.
TL;DR: In this paper, the authors present the current knowledge of the prevalence and risk factors for colonization by multidrug-resistant organisms in long-term care facilities (LTCF), thereby providing a useful reference to establish objectives for implementing successful antimicrobial stewardship programs (ASPs).
Abstract: Elderly people confined to chronic care facilities face an increased risk of acquiring infections by multidrug-resistant organisms (MDROs). This review presents the current knowledge of the prevalence and risk factors for colonization by MDROs in long-term care facilities (LTCF), thereby providing a useful reference to establish objectives for implementing successful antimicrobial stewardship programs (ASPs). We searched in PubMed and Scopus for studies examining the prevalence of MDROs and/or risk factors for the acquisition of MDROs in LTCF. One hundred and thirty-four studies published from 1987 to 2020 were included. The prevalence of MDROs in LTCF varies between the different continents, where Asia reported the highest prevalence of extended-spectrum s-lactamase (ESBL) Enterobacterales (71.6%), carbapenem resistant (CR) Enterobacterales (6.9%) and methicillin-resistant Staphylococcus aureus (MRSA) (25.6%) and North America the highest prevalence to MDR Pseudomonas aeruginosa (5.4%), MDR Acinetobacter baumannii (15.0%), vancomycin-resistant Enterococcus spp. (VRE) (4.0%), and Clostridioides difficile (26.1%). Furthermore, MDRO prevalence has experienced changes over time, with increases in MDR P. aeruginosa and extended spectrum s-lactamase producing Enterobacterales observed starting in 2015 and decreases of CR Enterobacterales, MDR A. baumannii, VRE, MRSA and C. difficile. Several risk factors have been found, such as male sex, chronic wounds, the use of medical devices, and previous antibiotic use. The last of these aspects represents one of the most important modifiable factors for reducing colonization with MDROs through implementing ASPs in LTCF.
TL;DR: In this paper, the authors summarized data from 73 scientific studies reporting antimicrobial residues in animal products that were freely available for sale, starting from 1999 to 2021 and identified through the Pubmed search engine.
Abstract: The extensive use of antibiotics leads to antibiotic residues in frequently consumed foods. Generally, the main use of antibiotics in animals is to treat and prevent diseases and growth promotion. However, the residues and their breakdown products have several side effects on the human body and, in a broader sense, on the environment. In relation to the human body, the frequency of mutations is increased, the bone marrow is damaged (chloramphenicol), and the reproductive organs of humans are affected. Carcinogenic effects have been found with antibiotics such as sulfamethazine, oxytetracycline, and furazolidone. We summarized data from 73 scientific studies reporting antimicrobial residues in animal products that were freely available for sale. The studies were published in English starting from 1999 till 2021 and identified through the Pubmed search engine. The aims were to find out which antibiotics, legal or illegal, could be found in animal foods worldwide. Which are stable to get into the food chain and exceed the maximum residue limits (MRL) regarding the EU guidelines as a comparison. Reducing antimicrobial residues in food from animal origin and, in addition to this, fighting the tremendous growth and spread of antimicrobial resistance will undoubtedly be one of the most difficult food safety challenges in the coming years.
TL;DR: In this article, the mechanism of action of Ivermectin against SARS-CoV-2 and summarizing the available literature over the years is discussed, and a schematic of the key cellular and biomolecular interactions between Iversectin, host cell, and SARS CoV2 in COVID-19 pathogenesis and prevention of complications have been proposed.
Abstract: Considering the urgency of the ongoing COVID-19 pandemic, detection of various new mutant strains and future potential re-emergence of novel coronaviruses, repurposing of approved drugs such as Ivermectin could be worthy of attention. This evidence-based review article aims to discuss the mechanism of action of ivermectin against SARS-CoV-2 and summarizing the available literature over the years. A schematic of the key cellular and biomolecular interactions between Ivermectin, host cell, and SARS-CoV-2 in COVID-19 pathogenesis and prevention of complications have been proposed.
TL;DR: In this article, the authors investigated the impact of the COVID-19 pandemic on infections and antibiotic prescribing in Dutch primary care and found that the number of infectious disease episodes treated with antibiotics decreased.
Abstract: In 2020, the COVID-19 pandemic brought dramatic changes in the delivery of primary health care across the world, presumably changing the number of consultations for infectious diseases and antibiotic use. We aimed to assess the impact of the pandemic on infections and antibiotic prescribing in Dutch primary care. All patients included in the routine health care database of the Julius General Practitioners' Network were followed from March through May 2019 (n = 389,708) and March through May 2020 (n = 405,688). We extracted data on consultations for respiratory/ear, urinary tract, gastrointestinal and skin infections using the International Classification of Primary Care (ICPC) codes. These consultations were combined in disease episodes and linked to antibiotic prescriptions. The numbers of infectious disease episodes (total and those treated with antibiotics), complications, and antibiotic prescription rates (i.e., proportion of episodes treated with antibiotics) were calculated and compared between the study periods in 2019 and 2020. Fewer episodes were observed during the pandemic months than in the same months in 2019 for both the four infectious disease entities and complications such as pneumonia, mastoiditis and pyelonephritis. The largest decline was seen for gastrointestinal infections (relative risk (RR), 0.54; confidence interval (CI), 0.51 to 0.58) and skin infections (RR, 0.71; CI, 0.67 to 0.75). The number of episodes treated with antibiotics declined as well, with the largest decrease seen for respiratory/ear infections (RR, 0.54; CI, 0.52 to 0.58). The antibiotic prescription rate for respiratory/ear infections declined from 21% to 13% (difference -8.0% (CI, -8.8 to -7.2)), yet the prescription rates for other infectious disease entities remained similar or increased slightly. The decreases in primary care infectious disease episodes and antibiotic use were most pronounced in weeks 15-19, mid-COVID-19 wave, after an initial peak in respiratory/ear infection presentation in week 11, the first week of lock-down. In conclusion, our findings indicate that the COVID-19 pandemic has had profound effects on the presentation of infectious disease episodes and antibiotic use in primary care in the Netherlands. Consequently, the number of infectious disease episodes treated with antibiotics decreased. We found no evidence of an increase in complications.
TL;DR: In this paper, the primary role of Actinomycetes in the history of antibiotics is described thoroughly and how their chemical structures have inspired generations of scientists working in the synthesis of new drugs are described thoroughly.
Abstract: The discovery of penicillin by Sir Alexander Fleming in 1928 provided us with access to a new class of compounds useful at fighting bacterial infections: antibiotics. Ever since, a number of studies were carried out to find new molecules with the same activity. Microorganisms belonging to Actinobacteria phylum, the Actinomycetes, were the most important sources of antibiotics. Bioactive compounds isolated from this order were also an important inspiration reservoir for pharmaceutical chemists who realized the synthesis of new molecules with antibiotic activity. According to the World Health Organization (WHO), antibiotic resistance is currently one of the biggest threats to global health, food security, and development. The world urgently needs to adopt measures to reduce this risk by finding new antibiotics and changing the way they are used. In this review, we describe the primary role of Actinomycetes in the history of antibiotics. Antibiotics produced by these microorganisms, their bioactivities, and how their chemical structures have inspired generations of scientists working in the synthesis of new drugs are described thoroughly.
TL;DR: Wang et al. as discussed by the authors developed a nanocomposite scaffold composed of chitosan (CS), polyvinyl alcohol (PVA), and phytogenic iron oxide nanoparticles (FeO NPs), for accelerated anemia-associated diabetic wound healing.
Abstract: Diabetic and anemia-associated diabetic wounds increase the considerable morbidity and mortality in people, as reported by clinical studies. However, no anemia-associated diabetic wound dressing materials have been developed until now. Hence, this study aimed to develop a nanocomposite scaffold composed of chitosan (CS), poly (vinyl alcohol) (PVA), and phytogenic iron oxide nanoparticles (FeO NPs), for accelerated anemia-associated diabetic wound healing. The aqueous leaves extract of Pinus densiflora (PD) was utilized for the synthesis of iron oxide nanoparticles (FeO NPs). TEM and elemental analysis confirmed smaller size PD-FeO NPs (<50 nm) synthesis with the combination of iron and oxide. In addition, in vitro biological studies displayed the moderate antioxidant, antidiabetic activities, and considerable antibacterial activity of PD-FeO NPs. Further, the different concentrations of PD-FeO NPs (0.01, 0.03, and 0.05%) incorporated CS/PVA nanocomposites sponges were developed by the freeze-drying method. The porous structured morphology and the presence of PD-FeO NPs were observed under FE-SEM. Among nanocomposite sponges, PD-FeO NPs (0.01%) incorporated CS/PVA sponges were further chosen for the in vitro wound-healing assay, based on the porous and water sorption nature. Furthermore, the in vitro wound-healing assay revealed that PD-FeO NPs (0.01%) incorporated CS/PVA has significantly increased the cell proliferation in HEK293 cells. In conclusion, the CS/PVA-PD-FeO NPs (0.01%) sponge would be recommended for diabetic wound dressing after a detailed in vivo evaluation.
TL;DR: In this paper, the current status and suitability of the thiamine pyrophosphate (TPP), flavin mononucleotide (FMN), glmS, guanine, and other riboswitches as antibacterial targets are discussed.
Abstract: Riboswitches reside in the untranslated region of RNA and regulate genes involved in the biosynthesis of essential metabolites through binding of small molecules. Since their discovery at the beginning of this century, riboswitches have been regarded as potential antibacterial targets. Using fragment screening, high-throughput screening and rational ligand design guided by X-ray crystallography, lead compounds against various riboswitches have been identified. Here, we review the current status and suitability of the thiamine pyrophosphate (TPP), flavin mononucleotide (FMN), glmS, guanine, and other riboswitches as antibacterial targets and discuss them in a biological context. Further, we highlight challenges in riboswitch drug discovery and emphasis the need to develop riboswitch specific high-throughput screening methods.
TL;DR: In this article, the authors established the relationship between biofilm-forming capacity, the expression of some important virulence factors, and the multidrug-resistant (MDR) phenotype in Pseudomonas aeruginosa.
Abstract: Pseudomonas aeruginosa (P. aeruginosa) possesses a plethora of virulence determinants, including the production of biofilm, pigments, exotoxins, proteases, flagella, and secretion systems. The aim of our present study was to establish the relationship between biofilm-forming capacity, the expression of some important virulence factors, and the multidrug-resistant (MDR) phenotype in P. aeruginosa. A total of three hundred and two (n = 302) isolates were included in this study. Antimicrobial susceptibility testing and phenotypic detection of resistance determinants were carried out; based on these results, isolates were grouped into distinct resistotypes and multiple antibiotic resistance (MAR) indices were calculated. The capacity of isolates to produce biofilm was assessed using a crystal violet microtiter-plate based method. Motility (swimming, swarming, and twitching) and pigment-production (pyoverdine and pyocyanin) were also measured. Pearson correlation coefficients (r) were calculated to determine for antimicrobial resistance, biofilm-formation, and expression of other virulence factors. Resistance rates were the highest for ceftazidime (56.95%; n = 172), levofloxacin (54.97%; n = 166), and ciprofloxacin (54.64%; n = 159), while lowest for colistin (1.66%; n = 5); 44.04% (n = 133) of isolates were classified as MDR. 19.87% (n = 60), 20.86% (n = 63) and 59.27% (n = 179) were classified as weak, moderate, and strong biofilm producers, respectively. With the exception of pyocyanin production (0.371 ± 0.193 vs. non-MDR: 0.319 ± 0.191; p = 0.018), MDR and non-MDR isolates did not show significant differences in expression of virulence factors. Additionally, no relevant correlations were seen between the rate of biofilm formation, pigment production, or motility. Data on interplay between the presence and mechanisms of drug resistance with those of biofilm formation and virulence is crucial to address chronic bacterial infections and to provide strategies for their management.
TL;DR: The third International Symposium on Alternatives to Antibiotics: Challenges and Solutions in Animal Health and Production as mentioned in this paper was organized by the USDA Agricultural Research Service, Faculty of Veterinary Science, Chulalongkorn University and Department of Livestock Development-Thailand Ministry of Agriculture and Cooperative, supported by OIE World Organization for Animal Health.
Abstract: Antibiotics have improved the length and quality of life of people worldwide and have had an immeasurable influence on agricultural animal health and the efficiency of animal production over the last 60 years. The increased affordability of animal protein for a greater proportion of the global population, in which antibiotic use has played a crucial part, has resulted in a substantial improvement in human quality of life. However, these benefits have come with major unintended consequences, including antibiotic resistance. Despite the inherent benefits of restricting antibiotic use in animal production, antibiotics remain essential to ensuring animal health, necessitating the development of novel approaches to replace the prophylactic and growth-promoting benefits of antibiotics. The third International Symposium on “Alternatives to Antibiotics: Challenges and Solutions in Animal Health and Production” in Bangkok, Thailand was organized by the USDA Agricultural Research Service, Faculty of Veterinary Science, Chulalongkorn University and Department of Livestock Development-Thailand Ministry of Agriculture and Cooperative; supported by OIE World Organization for Animal Health; and attended by more than 500 scientists from academia, industry, and government from 32 nations across 6 continents. The focus of the symposium was on ensuring human and animal health, food safety, and improving food animal production efficiency as well as quality. Attendees explored six subject areas in detail through scientific presentations and panel discussions with experts, and the major conclusions were as follows: (1) defining the mechanisms of action of antibiotic alternatives is paramount to enable their effective use, whether they are used for prevention, treatment, or to enhance health and production; (2) there is a need to integrate nutrition, health, and disease research, and host genetics needs to be considered in this regard; (3) a combination of alternatives to antibiotics may need to be considered to achieve optimum health and disease management in different animal production systems; (4) hypothesis-driven field trials with proper controls are needed to validate the safety, efficacy, and return of investment (ROI) of antibiotic alternatives.
TL;DR: In this article, the authors present and discuss the recent progress in the preparation and application of metal-based nanoparticles biogenically synthesized for antibacterial and antivirus applications.
Abstract: Much progress has been achieved in the preparation and application of engineered nanoparticles (NPs) in the field of medicine, mainly for antibacterial and antiviral applications. In the war against bacteria and viruses, besides traditional antibiotics and antiviral drugs, metal-based nanoparticles, such as silver (AgNPs), copper (CuNPs), copper oxides (CuO-NPs), iron oxide (FeO-NPs), zinc oxide (ZnO-NPs), and titanium oxide (TiO2-NPs) have been used as potent antimicrobial agents. These nanoparticles can be synthesized by traditional methods, such as chemical and physical routes, or more recently by biogenic processes. A great variety of macro and microorganisms can be successfully used as reducing agents of metal salt precursors in the biogenic synthesis of metal-based NPs for antimicrobial activity. Depending on the nature of the biological agent, NPs with different sizes, aggregation states, morphology, surface coatings and charges can be obtained, leading to different antimicrobial effects. Considering the drug resistance to traditional therapies, the development of versatile nanomaterials with potent antimicrobial effects is under intensive investigation. In this sense, this review presents and discusses the recent progress in the preparation and application of metal-based nanoparticles biogenically synthesized for antibacterial and antivirus applications. The strength and limitations are critically discussed.
TL;DR: In this article, a series of hybrid sulfaguanidine moieties, bearing 2-cyanoacrylamide 2a-d, pyridine-2-one 3-10, and 2-imino-2H-chromene-3-carboxamide 11, 12 derivatives, were synthesized, and their structure confirmed by spectral data and elemental analysis.
Abstract: Herein, a series of novel hybrid sulfaguanidine moieties, bearing 2-cyanoacrylamide 2a-d, pyridine-2-one 3-10, and 2-imino-2H-chromene-3-carboxamide 11, 12 derivatives, were synthesized, and their structure confirmed by spectral data and elemental analysis All the synthesized compounds showed moderate to good antimicrobial activity against eight pathogens The most promising six derivatives, 2a, 2b, 2d, 3a, 8, and 11, revealed to be best in inhibiting bacterial and fungal growth, thus showing bactericidal and fungicidal activity These derivatives exhibited moderate to potent inhibition against DNA gyrase and DHFR enzymes, with three derivatives 2d, 3a, and 2a demonstrating inhibition of DNA gyrase, with IC50 values of 1817-2387 µM, and of DHFR, with IC50 values of 433-554 µM; their potency is near to that of the positive controls Further, the six derivatives exhibited immunomodulatory potential and three derivatives, 2d, 8, and 11, were selected for further study and displayed an increase in spleen and thymus weight and enhanced the activation of CD4+ and CD8+ T lymphocytes Finally, molecular docking and some AMED studies were performed
TL;DR: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020 as discussed by the authors.
Abstract: Background: Bacterial antibiotic resistance changes over time depending on multiple factors; therefore, it is essential to monitor the susceptibility trends to reduce the resistance impact on the effectiveness of various treatments. Objective: To conduct a time-trend analysis of Helicobacter pylori resistance to antibiotics in Europe. Methods: The international prospective European Registry on Helicobacter pylori Management (Hp-EuReg) collected data on all infected adult patients diagnosed with culture and antimicrobial susceptibility testing positive results that were registered at AEG-REDCap e-CRF until December 2020. Results: Overall, 41,562 patients were included in the Hp-EuReg. Culture and antimicrobial susceptibility testing were performed on gastric biopsies of 3974 (9.5%) patients, of whom 2852 (7%) were naive cases included for analysis. The number of positive cultures decreased by 35% from the period 2013-2016 to 2017-2020. Concerning naive patients, no antibiotic resistance was found in 48% of the cases. The most frequent resistances were reported against metronidazole (30%), clarithromycin (25%), and levofloxacin (20%), whereas resistances to tetracycline and amoxicillin were below 1%. Dual and triple resistances were found in 13% and 6% of the cases, respectively. A decrease (p < 0.001) in the metronidazole resistance rate was observed between the 2013-2016 (33%) and 2017-2020 (24%) periods. Conclusion: Culture and antimicrobial susceptibility testing for Helicobacter pylori are scarcely performed (<10%) in Europe. In naive patients, Helicobacter pylori resistance to clarithromycin remained above 15% throughout the period 2013-2020 and resistance to levofloxacin, as well as dual or triple resistances, were high. A progressive decrease in metronidazole resistance was observed.
TL;DR: In this paper, mice were fed dextran sodium sulfate (DSS) solution for 5 days, followed by 5 days of normal drinking water, to investigate the gut microbiota response to colitis and the initial alteration of microbiota in recovery phase.
Abstract: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic and relapsing inflammation within the gastrointestinal tract. Antibiotics have been used to treat IBD, primarily utilizing metronidazole. Although there does seem to be a treatment effect, the broad-spectrum antibiotics that have been used to date are crude tools and have many adverse effects. Available evidence suggests that the host microbiome is implicated in the pathogenesis of IBD, though the key bacteria remain unknown. If the bacterial population can be modified appropriately, the use of antibiotics will have a better therapeutic effect. In this study, mice were fed dextran sodium sulfate (DSS) solution for 5 days, followed by 5 days of normal drinking water, to investigate the gut microbiota response to colitis and the initial alteration of microbiota in recovery phase. Day 0 was considered the normal control, while day 5 and day 10 were considered the colitis mouse model progressive phase and recovery phase, respectively. Results showed that inflammation could induce proportional changes in the gut microbiota. Furthermore, transplanting the microbiota in progressive phase to antibiotic-induced microbiota-depleted mice could induce inflammation similar to colitis, which proves the importance of initial alteration of the microbiota for IBD recovery and the potential of the microbiota as a target for the treatment of IBD. Meanwhile, we have also identified three possible target microorganisms in the development of colitis, namely genera Muribaculaceae (negative correlation), Turicibacter (positive correlation) and Lachnospiraceae (negative correlation) in inflammation status through comprehensive analysis.
TL;DR: In this article, the authors review the mechanism of action of antibiotics from different classes and discuss insights into the well-established primary targets in Staphylococcus aureus, including cell wall synthesis, protein synthesis (translation), DNA replication, RNA synthesis (transcription), and metabolic processes, such as folic acid synthesis.
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent bacterial pathogens and continues to be a leading cause of morbidity and mortality worldwide. MRSA is a commensal bacterium in humans and is transmitted in both community and healthcare settings. Successful treatment remains a challenge, and a search for new targets of antibiotics is required to ensure that MRSA infections can be effectively treated in the future. Most antibiotics in clinical use selectively target one or more biochemical processes essential for S. aureus viability, e.g., cell wall synthesis, protein synthesis (translation), DNA replication, RNA synthesis (transcription), or metabolic processes, such as folic acid synthesis. In this review, we briefly describe the mechanism of action of antibiotics from different classes and discuss insights into the well-established primary targets in S. aureus. Further, several components of bacterial cellular processes, such as teichoic acid, aminoacyl-tRNA synthetases, the lipid II cycle, auxiliary factors of β-lactam resistance, two-component systems, and the accessory gene regulator quorum sensing system, are discussed as promising targets for novel antibiotics. A greater molecular understanding of the bacterial targets of antibiotics has the potential to reveal novel therapeutic strategies or identify agents against antibiotic-resistant pathogens.
TL;DR: A review of extremophilic actinobacteria found in various unique and extreme niches is presented in this article, focusing on the diversity and bioactive potentials/medically relevant biomolecules.
Abstract: Actinobacteria constitute prolific sources of novel and vital bioactive metabolites for pharmaceutical utilization. In recent years, research has focused on exploring actinobacteria that thrive in extreme conditions to unearth their beneficial bioactive compounds for natural product drug discovery. Natural products have a significant role in resolving public health issues such as antibiotic resistance and cancer. The breakthrough of new technologies has overcome the difficulties in sampling and culturing extremophiles, leading to the outpouring of more studies on actinobacteria from extreme environments. This review focuses on the diversity and bioactive potentials/medically relevant biomolecules of extremophilic actinobacteria found from various unique and extreme niches. Actinobacteria possess an excellent capability to produce various enzymes and secondary metabolites to combat harsh conditions. In particular, a few strains have displayed substantial antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), shedding light on the development of MRSA-sensitive antibiotics. Several strains exhibited other prominent bioactivities such as antifungal, anti-HIV, anticancer, and anti-inflammation. By providing an overview of the recently found extremophilic actinobacteria and their important metabolites, we hope to enhance the understanding of their potential for the medical world.