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1.
Antimicrob Resist Infect Control ; 11(1): 45, 2022 03 07.
Article in English | MEDLINE | ID: covidwho-1731546

ABSTRACT

BACKGROUND: Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). OBJECTIVES: We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. METHODS: We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. RESULTS: Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8-40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1-0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. CONCLUSIONS: During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.


Subject(s)
Bacteria/drug effects , Bacterial Infections/drug therapy , COVID-19/complications , Drug Resistance, Bacterial , Drug Resistance, Fungal , Mycoses/drug therapy , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bacterial Infections/etiology , Bacterial Infections/microbiology , COVID-19/virology , Fungi/classification , Fungi/drug effects , Fungi/genetics , Fungi/isolation & purification , Humans , Mycoses/etiology , Mycoses/microbiology , SARS-CoV-2/physiology
2.
PLoS One ; 16(9): e0257085, 2021.
Article in English | MEDLINE | ID: covidwho-1690808

ABSTRACT

A kiosk-based survey at the American Museum of Natural History in New York City in 2016-2018 allowed us to assess public knowledge of antibiotics and public attitudes toward microbes in museum goers. Over 22,000 visitors from 172 countries and territories answered several carefully designed questions about microbes and antibiotics. These visitors also entered age, gender, and country demographic data that allowed for stratification along these demographic and geographic divisions. Because museum goers are likely to be better informed about these and other science-based topics, the results described here can set a potential upper bound for public knowledge on these topics. Surprisingly, the results of our analysis of museum goers' answers about microbes and antibiotics indicate a substantial lack of familiarity with both topics. For example, overall only about 50% of respondents can correctly identify penicillin as an antibiotic and less than 50% of museum visitors view microbes as beneficial. The results described here suggest that we are perhaps off target with our educational efforts in this area and that a major shift in approach toward more basic microbial topics is warranted in our educational efforts.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Health Knowledge, Attitudes, Practice , Museums , Natural History , Perception , Surveys and Questionnaires , Data Analysis , Humans , Language
3.
ACS Appl Mater Interfaces ; 14(1): 49-56, 2022 Jan 12.
Article in English | MEDLINE | ID: covidwho-1608662

ABSTRACT

The development of low-cost, non-toxic, scalable antimicrobial textiles is needed to address the spread of deadly pathogens. Here, we report a polysiloxane textile coating that possesses two modes of antimicrobial inactivation, passive contact inactivation through amine/imine functionalities and active photodynamic inactivation through the generation of reactive oxygen species (ROS). This material can be coated and cross-linked onto natural and synthetic textiles through a simple soak procedure, followed by UV cure to afford materials exhibiting no aqueous leaching and only minimal leaching in organic solvents. This coating minimally impacts the mechanical properties of the fabric while also imparting hydrophobicity. Passive inactivation of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) is achieved with >98% inactivation after 24 h, with a 23× and 3× inactivation rate increase against E. coli and MRSA, respectively, when green light is used to generate ROS. Up to 90% decrease in the infectivity of SARS-CoV-2 after 2 h of irradiated incubation with the material is demonstrated. These results show that modifying textiles with dual-functional polymers results in robust and highly antimicrobial materials that are expected to find widespread use in combating the spread of deadly pathogens.


Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , Coated Materials, Biocompatible/chemistry , Polymers/chemistry , SARS-CoV-2/drug effects , Textiles/analysis , Anti-Infective Agents/chemistry , COVID-19/prevention & control , COVID-19/virology , Coated Materials, Biocompatible/pharmacology , Escherichia coli/drug effects , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Photochemotherapy/methods , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification , Textiles/toxicity , Ultraviolet Rays
4.
Molecules ; 27(1)2021 Dec 29.
Article in English | MEDLINE | ID: covidwho-1607266

ABSTRACT

The rising tide of antibacterial drug resistance has given rise to the virtual elimination of numerous erstwhile antibiotics, intensifying the urgent demand for novel agents. A number of drugs have been found to possess potent antimicrobial action during the past several years and have the potential to supplement or even replace the antibiotics. Many of these 'non-antibiotics', as they are referred to, belong to the widely used class of neuroleptics, the phenothiazines. Another chemically and pharmacologically related class is the thioxanthenes, differing in that the aromatic N of the central phenothiazine ring has been replaced by a C atom. Such "carbon-analogues" were primarily synthesized with the hope that these would be devoid of some of the toxic effects of phenothiazines. Intensive studies on syntheses, as well as chemical and pharmacological properties of thioxanthenes, were initiated in the late 1950s. Although a rather close parallelism with respect to structure activity relationships could be observed between phenothiazines and thioxanthenes; several thioxanthenes were synthesized in pharmaceutical industries and applied for human use as neuroleptics. Antibacterial activities of thioxanthenes came to be recognized in the early 1980s in Europe. During the following years, many of these drugs were found not only to be antibacterial agents but also to possess anti-mycobacterial, antiviral (including anti-HIV and anti-SARS-CoV-2) and anti-parasitic properties. Thus, this group of drugs, which has an inhibitory effect on the growth of a wide variety of microorganisms, needs to be explored for syntheses of novel antimicrobial agents. The purpose of this review is to summarize the neuroleptic and antimicrobial properties of this exciting group of bioactive molecules with a goal of identifying potential structures worthy of future exploration.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antipsychotic Agents/pharmacology , Bacteria/drug effects , Psychotic Disorders/drug therapy , Thioxanthenes/pharmacology , Animals , Humans , Microbiota
5.
Bioorg Chem ; 119: 105550, 2022 02.
Article in English | MEDLINE | ID: covidwho-1561636

ABSTRACT

Infectious diseases caused by new or unknown bacteria and viruses, such as anthrax, cholera, tuberculosis and even COVID-19, are a major threat to humanity. Thus, the development of new synthetic compounds with efficient antimicrobial activity is a necessity. Herein, rationally designed novel multifunctional cationic alternating copolymers were directly synthesized through a step-growth polymerization reaction using a bivalent electrophilic cross-linker containing disulfide bonds and a diamine heterocyclic ring. To optimize the activity of these alternating copolymers, several different diamines and cross-linkers were explored to find the highest antibacterial effects. The synthesized nanopolymers not only displayed good to excellent antibacterial activity as judged by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli, but also reduced the number of biofilm cells even at low concentrations, without killing mammalian cells. Furthermore, in vivo experiments using infected burn wounds in mice demonstrated good antibacterial activity and stimulated wound healing, without causing systemic inflammation. These findings suggest that the multifunctional cationic nanopolymers have potential as a novel antibacterial agent for eradication of multidrug resistant bacterial infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Biofilms/drug effects , Cations/pharmacology , Polymers/pharmacology , Wound Healing/drug effects , Amines/chemistry , Animals , Bacteria/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/etiology , Burns/complications , COVID-19 , Cell Survival/drug effects , Cross-Linking Reagents , Drug Resistance, Multiple, Bacterial/drug effects , HEK293 Cells/drug effects , Humans , Mice , Microbial Sensitivity Tests , Polymers/chemistry
6.
Microbiol Spectr ; 9(3): e0028321, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1501550

ABSTRACT

The Infectious Disease Surveillance of Pediatrics (ISPED) program was established in 2015 to monitor and analyze the trends of bacterial epidemiology and antimicrobial resistance (AMR) in children. Clinical bacterial isolates were collected from 11 tertiary care children's hospitals in China in 2016 to 2020. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer method or automated systems, with interpretation according to the Clinical and Laboratory Standards Institute 2019 breakpoints. A total of 288,377 isolates were collected, and the top 10 predominant bacteria were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii. In 2020, the coronavirus disease 2019 (COVID-19) pandemic year, we observed a significant reduction in the proportion of respiratory tract samples (from 56.9% to 44.0%). A comparable reduction was also seen in the primary bacteria mainly isolated from respiratory tract samples, including S. pneumoniae, H. influenzae, and S. pyogenes. Multidrug-resistant organisms (MDROs) in children were commonly observed and presented higher rates of drug resistance than sensitive strains. The proportions of carbapenem-resistant K. pneumoniae (CRKP), carbapenem-resistant A. baumannii (CRAB), carbapenem-resistant P. aeruginosa (CRPA), and methicillin-resistant S. aureus (MRSA) strains were 19.7%, 46.4%%, 12.8%, and 35.0%, respectively. The proportions of CRKP, CRAB, and CRPA strains all showed decreasing trends between 2015 and 2020. Carbapenem-resistant Enterobacteriaceae (CRE) and CRPA gradually decreased with age, while CRAB showed the opposite trend with age. Both CRE and CRPA pose potential threats to neonates. MDROs show very high levels of AMR and have become an urgent threat to children, suggesting that effective monitoring of AMR and antimicrobial stewardship among children in China are required. IMPORTANCE AMR, especially that involving multidrug-resistant organisms (MDROs), is recognized as a global threat to human health; AMR renders infections increasingly difficult to treat, constituting an enormous economic burden and producing tremendous negative impacts on patient morbidity and mortality rates. There are many surveillance programs in the world to address AMR profiles and MDRO prevalence in humans. However, published studies evaluating the overall AMR rates or MDRO distributions in children are very limited or are of mixed quality. In this study, we showed the bacterial epidemiology and resistance profiles of primary pathogens in Chinese children from 2016 to 2020 for the first time, analyzed MDRO distributions with time and with age, and described MDROs' potential threats to children, especially low-immunity neonates. Our study will be very useful to guide antiinfection therapy in Chinese children, as well as worldwide pediatric patients.


Subject(s)
Bacteria/classification , Communicable Diseases/epidemiology , Communicable Diseases/microbiology , Drug Resistance, Bacterial , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacteria/isolation & purification , COVID-19/epidemiology , Child , China/epidemiology , Drug Resistance, Bacterial/drug effects , Escherichia coli/drug effects , Humans , Klebsiella pneumoniae/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Moraxella catarrhalis , Pseudomonas aeruginosa/drug effects , SARS-CoV-2 , Staphylococcus aureus/drug effects , Staphylococcus epidermidis , Streptococcus pneumoniae , Streptococcus pyogenes
7.
Photochem Photobiol Sci ; 20(11): 1497-1545, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1491552

ABSTRACT

Photodynamic therapy is witnessing a revival of its origins as a response to the rise of multi-drug resistant infections and the shortage of new classes of antibiotics. Photodynamic disinfection (PDDI) of microorganisms is making progresses in preclinical models and in clinical cases, and the perception of its role in the clinical armamentarium for the management of infectious diseases is changing. We review the positioning of PDDI from the perspective of its ability to respond to clinical needs. Emphasis is placed on the pipeline of photosensitizers that proved effective to inactivate biofilms, showed efficacy in animal models of infectious diseases or reached clinical trials. Novel opportunities resulting from the COVID-19 pandemic are briefly discussed. The molecular features of promising photosensitizers are emphasized and contrasted with those of photosensitizers used in the treatment of solid tumors. The development of photosensitizers has been accompanied by the fabrication of a variety of affordable and customizable light sources. We critically discuss the combination between photosensitizer and light source properties that may leverage PDDI and expand its applications to wider markets. The success of PDDI in the management of infectious diseases will ultimately depend on the efficacy of photosensitizers, affordability of the light sources, simplicity of the procedures, and availability of fast and efficient treatments.


Subject(s)
Communicable Disease Control/methods , Drug Resistance, Microbial/drug effects , Drug Resistance, Multiple/drug effects , Photochemotherapy , Photosensitizing Agents/therapeutic use , Animals , Bacteria/drug effects , Biofilms/drug effects , Fungi/drug effects , Humans , Microbial Sensitivity Tests , Neoplasms/drug therapy , Photosensitizing Agents/pharmacology
8.
J Am Chem Soc ; 143(43): 17891-17909, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1483091

ABSTRACT

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.


Subject(s)
Anti-Infective Agents/chemistry , Drug Design , Phototherapy/methods , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Bacteria/drug effects , Biofilms/drug effects , Biofilms/radiation effects , Coloring Agents/chemistry , Coloring Agents/pharmacology , Equipment and Supplies/microbiology , Equipment and Supplies/virology , Escherichia coli/drug effects , Escherichia coli/physiology , Eye Diseases/drug therapy , Eye Diseases/pathology , Fungi/drug effects , Graphite/chemistry , Light , Nanoparticles/chemistry , Nanoparticles/toxicity , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Quantum Theory , Reactive Oxygen Species/metabolism , Viruses/drug effects
9.
Viruses ; 13(11)2021 10 20.
Article in English | MEDLINE | ID: covidwho-1481016

ABSTRACT

Antimicrobial resistance is an urgent threat to public health and global development; in this scenario, the SARS-CoV2 pandemic has caused a major disruption of healthcare systems and practices. A narrative review was conducted on articles focusing on the impact of COVID-19 on multidrug-resistant gram-negative, gram-positive bacteria, and fungi. We found that, worldwide, multiple studies reported an unexpected high incidence of infections due to methicillin-resistant S. aureus, carbapenem-resistant A. baumannii, carbapenem-resistant Enterobacteriaceae, and C. auris among COVID-19 patients admitted to the intensive care unit. In this setting, inappropriate antimicrobial exposure, environmental contamination, and discontinuation of infection control measures may have driven selection and diffusion of drug-resistant pathogens.


Subject(s)
Bacterial Infections/microbiology , COVID-19/epidemiology , Coinfection/epidemiology , Drug Resistance, Bacterial , Drug Resistance, Fungal , Mycoses/microbiology , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacterial Infections/complications , Bacterial Infections/epidemiology , COVID-19/complications , Coinfection/microbiology , Drug Resistance, Multiple, Bacterial , Fungi/drug effects , Humans , Infection Control , Intensive Care Units , Mycoses/complications , Mycoses/epidemiology
10.
Int J Mol Sci ; 22(20)2021 Oct 16.
Article in English | MEDLINE | ID: covidwho-1480793

ABSTRACT

The rapid rise of multidrug-resistant (MDR) bacteria has once again caused bacterial infections to become a global health concern. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), offer a viable solution to these pathogens due to their diverse mechanisms of actions, which include direct killing as well as immunomodulatory properties (e.g., anti-inflammatory activity). HDPs may hence provide a more robust treatment of bacterial infections. In this review, the advent of and the mechanisms that lead to antibiotic resistance will be described. HDP mechanisms of antibacterial and immunomodulatory action will be presented, with specific examples of how the HDP aurein 2.2 and a few of its derivatives, namely peptide 73 and cG4L73, function. Finally, resistance that may arise from a broader use of HDPs in a clinical setting and methods to improve biocompatibility will be briefly discussed.


Subject(s)
Antimicrobial Cationic Peptides/immunology , Antimicrobial Cationic Peptides/pharmacology , Bacteria/drug effects , Bacteria/immunology , Bacterial Infections/drug therapy , Bacterial Infections/immunology , Immunomodulation , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/chemistry , Bacterial Infections/microbiology , Drug Resistance, Bacterial , Host Microbial Interactions , Humans , /pharmacology
11.
Molecules ; 26(19)2021 Oct 06.
Article in English | MEDLINE | ID: covidwho-1463769

ABSTRACT

Pristine high-density bulk disks of MgB2 with added hexagonal BN (10 wt.%) were prepared using spark plasma sintering. The BN-added samples are machinable by chipping them into desired geometries. Complex shapes of different sizes can also be obtained by the 3D printing of polylactic acid filaments embedded with MgB2 powder particles (10 wt.%). Our present work aims to assess antimicrobial activity quantified as viable cells (CFU/mL) vs. time of sintered and 3D-printed materials. In vitro antimicrobial tests were performed against the bacterial strains Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Enterococcus faecium DSM 13590, and Enterococcus faecalis ATCC 29212; and the yeast strain Candida parapsilosis ATCC 22019. The antimicrobial effects were found to depend on the tested samples and microbes, with E. faecium being the most resistant and E. coli the most susceptible.


Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , Boron Compounds/pharmacology , Fungi/drug effects , Magnesium Compounds/pharmacology , Candida parapsilosis/drug effects , Enterococcus faecalis/drug effects , Enterococcus faecium/drug effects , Escherichia coli/drug effects , Microbial Sensitivity Tests , Polyesters/pharmacology , Printing, Three-Dimensional , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects
12.
ChemMedChem ; 16(23): 3553-3558, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1437037

ABSTRACT

In the search for a fast contact-killing antimicrobial surface to break the transmission pathway of lethal pathogens, nanostructured copper surfaces were found to exhibit the desired antimicrobial properties. Compared with plain copper, these nanostructured copper surfaces with Cu(OH)2 nano-sword or CuO nano-foam were found to completely eliminate pathogens at a fast rate, including clinically isolated drug resistant species. Additionally these nanostructured copper surfaces demonstrated potential antiviral properties when assessed against bacteriophages, as a viral surrogate, and murine hepatitis virus, a surrogate for SARS-CoV-2. The multiple modes of killing, physical killing and copper ion mediated killing contribute to the superior and fast kinetics of antimicrobial action against common microbes, and ESKAPE pathogens. Prototypes for air and water cleaning with current nanostructured copper surface have also been demonstrated.


Subject(s)
Bacteria/drug effects , Copper/chemistry , Hepatitis Viruses/drug effects , Hydroxides/chemistry , Nanostructures/toxicity , SARS-CoV-2/drug effects , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Copper/pharmacology , Drug Resistance, Bacterial/drug effects , Mice , Microbial Sensitivity Tests , Nanostructures/chemistry , Surface Properties
13.
Ann Clin Microbiol Antimicrob ; 20(1): 69, 2021 Sep 25.
Article in English | MEDLINE | ID: covidwho-1438275

ABSTRACT

BACKGROUND: Coronavirus SARS-CoV-2 causes COVID-19 illness which can progress to severe pneumonia. Empiric antibacterials are often employed though frequency of bacterial coinfection superinfection is debated and concerns raised about selection of bacterial antimicrobial resistance. We evaluated sputum bacterial and fungal growth from 165 intubated COVID-19 pneumonia patients. Objectives were to determine frequency of culture positivity, risk factors for and outcomes of positive cultures, and timing of antimicrobial resistance development. METHODS: Retrospective reviews were conducted of COVID-19 pneumonia patients requiring intubation admitted to a 1058-bed four community hospital system on the east coast United States, March 1 to May 1, 2020. Length of stay (LOS) was expressed as mean (standard deviation); 95% confidence interval (95% CI) was computed for overall mortality rate using the exact binomial method, and overall mortality was compared across each level of a potential risk factor using a Chi-Square Test of Independence. All tests were two-sided, and significance level was set to 0.05. RESULTS: Average patient age was 68.7 years and LOS 19.9 days. Eighty-three patients (50.3% of total) originated from home, 10 from group homes (6.1% of total), and 72 from nursing facilities (43.6% of total). Mortality was 62.4%, highest for nursing home residents (80.6%). Findings from 253 sputum cultures overall did not suggest acute bacterial or fungal infection in 73 (45%) of 165 individuals sampled within 24 h of intubation. Cultures ≥ 1 week following intubation did grow potential pathogens in 72 (64.9%) of 111 cases with 70.8% consistent with late pneumonia and 29.2% suggesting colonization. Twelve (10.8% of total) of these late post-intubation cultures revealed worsened antimicrobial resistance predominantly in Pseudomonas, Enterobacter, or Staphylococcus aureus. CONCLUSIONS: In severe COVID-19 pneumonia, a radiographic ground glass interstitial pattern and lack of purulent sputum prior to/around the time of intubation correlated with no culture growth or recovery of normal oral flora ± yeast. Discontinuation of empiric antibacterials should be considered in these patients aided by other clinical findings, history of prior antimicrobials, laboratory testing, and overall clinical course. Continuing longterm hospitalisation and antibiotics are associated with sputum cultures reflective of hospital-acquired microbes and increasing antimicrobial resistance. TRIAL REGISTRATION: Not applicable as this was a retrospective chart review study without interventional arm.


Subject(s)
Bacteria/drug effects , Bacterial Infections/complications , COVID-19/therapy , Cross Infection/complications , Fungi/drug effects , Mycoses/complications , Pneumonia/therapy , Sputum/microbiology , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents , Anti-Infective Agents/pharmacology , Bacteria/genetics , Bacteria/isolation & purification , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Cross Infection/drug therapy , Cross Infection/microbiology , Drug Resistance, Bacterial , Drug Resistance, Multiple, Fungal , Female , Fungi/genetics , Fungi/isolation & purification , Hospitalization , Humans , Intubation , Length of Stay , Male , Middle Aged , Mycoses/microbiology , Pneumonia/complications , Pneumonia/mortality , Pneumonia/virology , Retrospective Studies , SARS-CoV-2/physiology
14.
Int Immunol ; 33(12): 787-790, 2021 11 25.
Article in English | MEDLINE | ID: covidwho-1398105

ABSTRACT

Dysbiosis is alterations in the microbial composition compared with a healthy microbiota and often features a reduction in gut microbial diversity and a change in microbial taxa. Dysbiosis, especially in the gut, has also been proposed to play a crucial role in the pathogenesis of a wide variety of diseases, including inflammatory bowel disease, colorectal cancer, cardiovascular disease, obesity, diabetes and multiple sclerosis. A body of evidence has shown that intestinal polymeric immunoglobulin A (IgA) antibodies are important to regulate the gut microbiota as well as to exclude pathogenic bacteria or viral infection such as influenza and SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) at mucosal sites. Since the 1970s, trials for oral administration of therapeutic IgA or IgG have been performed mainly to treat infectious enteritis caused by pathogenic Escherichia coli or Clostridium difficile. However, few of them have been successfully developed for clinical application up to now. In addition to the protective function against intestinal pathogens, IgA is well known to modulate the gut commensal microbiota leading to symbiosis. Nevertheless, the development of therapeutic IgA drugs to treat dysbiosis is not progressing. In this review, the advantages of therapeutic IgA antibodies and the problems for their development will be discussed.


Subject(s)
Bacteria/drug effects , Gastrointestinal Microbiome/drug effects , Immunoglobulin A/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Intestines/drug effects , Animals , Bacteria/immunology , Dysbiosis , Host-Pathogen Interactions , Humans , Immunoglobulin A/adverse effects , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/microbiology , Intestines/immunology , Intestines/microbiology , Species Specificity
15.
Biochem Soc Trans ; 49(5): 2411-2429, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1397910

ABSTRACT

The importance of vaccine-induced protection was repeatedly demonstrated over the last three decades and emphasized during the recent COVID-19 pandemic as the safest and most effective way of preventing infectious diseases. Vaccines have controlled, and in some cases, eradicated global viral and bacterial infections with high efficiency and at a relatively low cost. Carbohydrates form the capsular sugar coat that surrounds the outer surface of human pathogenic bacteria. Specific surface-exposed bacterial carbohydrates serve as potent vaccine targets that broadened our toolbox against bacterial infections. Since first approved for commercial use, antibacterial carbohydrate-based vaccines mostly rely on inherently complex and heterogenous naturally derived polysaccharides, challenging to obtain in a pure, safe, and cost-effective manner. The introduction of synthetic fragments identical with bacterial capsular polysaccharides provided well-defined and homogenous structures that resolved many challenges of purified polysaccharides. The success of semisynthetic glycoconjugate vaccines against bacterial infections, now in different phases of clinical trials, opened up new possibilities and encouraged further development towards fully synthetic antibacterial vaccine solutions. In this mini-review, we describe the recent achievements in semi- and fully synthetic carbohydrate vaccines against a range of human pathogenic bacteria, focusing on preclinical and clinical studies.


Subject(s)
Anti-Bacterial Agents/immunology , Bacteria/immunology , Bacterial Infections/immunology , Carbohydrates/immunology , Glycoconjugates/immunology , Vaccines, Synthetic/immunology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Carbohydrate Sequence , Carbohydrates/chemistry , Glycoconjugates/chemistry , Glycoconjugates/therapeutic use , Humans , Vaccines, Synthetic/chemistry , Vaccines, Synthetic/therapeutic use
16.
Photochem Photobiol Sci ; 20(7): 955-965, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1384775

ABSTRACT

The pandemic created by SARS-CoV-2 has caused a shortage in the supplies of N95 filtering facepiece respirators (FFRs), disposable respirators with at least 95% efficiency to remove non-oily airborne particles, due to increasing cases all over the world. The current article reviewed various possible decontamination methods for FFR reuse including ultraviolet germicidal irradiation (UVGI), hydrogen peroxide vapor (HPV), microwave-generated steam (MGS), hydrogen peroxide gas plasma (HPGP), and 70% or higher ethanol solution. HPV decontamination was effective against bacterial spores (6 log10 reduction of Geobacillus stearothermophilus spores) on FFRs and viruses (> 4 log10 reduction of various types of viruses) on inanimate surfaces, and no degradation of respirator materials and fit has been reported. 70% or higher ethanol decontamination showed high efficacy in inactivation of coronaviruses on inanimate surfaces (> 3.9 log10 reduction) but it was lower on FFRs which filtration efficiency was also decreased. UVGI method had good biocidal efficacy on FFRs (> 3 log10 reduction of H1N1 virus) combined with inexpensive, readily available equipment; however, it was more time-consuming to ensure sufficient reduction in SARS-CoV-2. MGS treatment also provided good viral decontamination on FFRs (> 4 log10 reduction of H1N1 virus) along with less time-intensive process and readily available equipment while inconsistent disinfection on the treated surfaces and deterioration of nose cushion of FFRs were observed. HPGP was a good virucidal system (> 6 log10 reduction of Vesicular stomatitis virus) but filtration efficiency after decontamination was inconsistent. Overall, HPV appeared to be one of the most promising methods based on the high biocidal efficacy on FFRs, preservation of respirator performance after multiple cycles, and no residual chemical toxicity. Nonetheless, equipment cost and time of the HPV process and a suitable operating room need to be considered.


Subject(s)
COVID-19 , Decontamination/methods , N95 Respirators/microbiology , N95 Respirators/virology , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/radiation effects , COVID-19/epidemiology , Disinfection/methods , Ethanol/pharmacology , Humans , Hydrogen Peroxide/pharmacology , Microwaves , Ultraviolet Rays , Viruses/drug effects , Viruses/isolation & purification , Viruses/radiation effects
17.
Molecules ; 26(15)2021 Jul 22.
Article in English | MEDLINE | ID: covidwho-1346513

ABSTRACT

Prunus mahaleb L. fruit has long been used in the production of traditional liqueurs. The fruit also displayed scavenging and reducing activity, in vitro. The present study focused on unravelling peripheral and central protective effects, antimicrobial but also anti-COVID-19 properties exerted by the water extract of P. mahaleb. Anti-inflammatory effects were studied in isolated mouse colons exposed to lipopolysaccharide. Neuroprotection, measured as a blunting effect on hydrogen-peroxide-induced dopamine turnover, was investigated in hypothalamic HypoE22 cells. Antimicrobial effects were tested against different Gram+ and Gram- bacterial strains. Whereas anti-COVID-19 activity was studied in lung adenocarcinoma H1299 cells, where the gene expression of ACE2 and TMPRSS2 was measured after extract treatment. The bacteriostatic effects induced on Gram+ and Gram- strains, together with the inhibition of COX-2, TNFα, HIF1α, and VEGFA in the colon, suggest the potential of P. mahaleb water extract in contrasting the clinical symptoms related to ulcerative colitis. The inhibition of the hydrogen peroxide-induced DOPAC/DA ratio indicates promising neuroprotective effects. Finally, the downregulation of the gene expression of ACE2 and TMPRSS2 in H1299 cells, suggests the potential to inhibit SARS-CoV-2 virus entry in the human host. Overall, the results support the valorization of the local cultivation of P. mahaleb.


Subject(s)
Bacteria/drug effects , Colon/drug effects , Neuroprotection , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/metabolism , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19 , Cell Line , Colitis, Ulcerative/drug therapy , Cytokines/genetics , Cytokines/metabolism , Dopamine/metabolism , Fruit/chemistry , Gene Expression Regulation/drug effects , HCT116 Cells , Humans , Inflammation/drug therapy , Male , Mice , Plant Extracts/chemistry , Prunus/chemistry , Serine Endopeptidases/metabolism
18.
Eur J Med Chem ; 224: 113696, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1300086

ABSTRACT

The antimicrobial resistance (AMR) is an intractable problem for the world. Metal ions are essential for the cell process and biological function in microorganisms. Many metal-based complexes with the potential for releasing ions are more likely to be absorbed for their higher lipid solubility. Hence, this review highlights the clinical potential of organometallic compounds for the treatment of infections caused by bacteria or fungi in recent five years. The common scaffolds, including antimicrobial peptides, N-heterocyclic carbenes, Schiff bases, photosensitive-grand-cycle skeleton structures, aliphatic amines-based ligands, and special metal-based complexes are summarized here. We also discuss their therapeutic targets and the risks that should be paid attention to in the future studies, aiming to provide information for researchers on metal-based complexes as antimicrobial agents and inspire the design and synthesis of new antimicrobial drugs.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacteria/drug effects , Drug Discovery , Fungi/drug effects , Organometallic Compounds/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Microbial Sensitivity Tests , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry
19.
mBio ; 12(1)2021 02 16.
Article in English | MEDLINE | ID: covidwho-1325089

ABSTRACT

The world faces two seemingly unrelated challenges-a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.


Subject(s)
Anti-Bacterial Agents , Drug Discovery/education , Science/education , Students , Bacteria/drug effects , Drug Discovery/methods , Humans
20.
Bioorg Chem ; 114: 105153, 2021 09.
Article in English | MEDLINE | ID: covidwho-1324044

ABSTRACT

A series of novel substituted phenyl 1, 3-thiazolidin-4-one sulfonyl derivatives 5 (a-t) were synthesized and screened for their in-vitro anti-microbial and anti-viral activity. The result of the anti-microbial assay demonstrated compounds 5d, 5f, 5g, 5h, 5i, 5j showed prominent inhibitory activity against all the tested Gram-positive and Gram-negative bacterial strains, while compounds 5g, 5j, 5o, 5p, 5q showed significant activity against the entire set of fungal strains as compared to standard drug Ampicillin and Clotrimazole, respectively. The antimicrobial study revealed that compounds having electron-withdrawing groups showed significant antimicrobial potency. The most active antibacterial compound 5j showed potent inhibition of S. aureus DNA Gyrase enzyme as a possible mechanism of action for antimicrobial activity. Moreover, the antiviral testing of selected compounds showed considerable activity against Herpes simplex virus-1(KOS), Herpes simplex virus-2 (G), Herpes simplex virus-1(TK- KOS ACVr), Vaccinia virus, Human Coronavirus (229E), Reovirus-1, Sindbis virus, Coxsackie virus B4, Yellow Fever virus and Influenza A, B virus. Compounds 5h exhibited low anti-viral activity against HIV-1(strain IIIB) and HIV-2 (strain ROD). The study clearly outlined that synthesized compounds endowed with good antimicrobial property together with considerable antiviral activity.


Subject(s)
Phenols/chemical synthesis , Sulfonamides/chemical synthesis , Toluene/analogs & derivatives , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Bacteria/classification , Bacteria/drug effects , Cell Line , Chlorocebus aethiops , Humans , Phenols/chemistry , Phenols/pharmacology , Sulfonamides/chemistry , Sulfonamides/pharmacology , Toluene/chemical synthesis , Toluene/chemistry , Toluene/pharmacology , Vero Cells , Viruses/classification , Viruses/drug effects
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