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1.
Antimicrob Resist Infect Control ; 11(1): 74, 2022 05 21.
Article in English | MEDLINE | ID: covidwho-1862157

ABSTRACT

BACKGROUND: Patients hospitalised for COVID-19 may present with or acquire bacterial or fungal infections that can affect the course of the disease. The aim of this study was to describe the microbiological characteristics of laboratory-confirmed infections in hospitalised patients with severe COVID-19. METHODS: We reviewed the hospital charts of a sample of patients deceased with COVID-19 from the Italian National COVID-19 Surveillance, who had laboratory-confirmed bacterial or fungal bloodstream infections (BSI) or lower respiratory tract infections (LRTI), evaluating the pathogens responsible for the infections and their antimicrobial susceptibility. RESULTS: Among 157 patients with infections hospitalised from February 2020 to April 2021, 28 (17.8%) had co-infections (≤ 48 h from admission) and 138 (87.9%) had secondary infections (> 48 h). Most infections were bacterial; LRTI were more frequent than BSI. The most common co-infection was pneumococcal LRTI. In secondary infections, Enterococci were the most frequently recovered pathogens in BSI (21.7% of patients), followed by Enterobacterales, mainly K. pneumoniae, while LRTI were mostly associated with Gram-negative bacteria, firstly Enterobacterales (27.4% of patients, K. pneumoniae 15.3%), followed by A. baumannii (19.1%). Fungal infections, both BSI and LRTI, were mostly due to C. albicans. Antibiotic resistance rates were extremely high in Gram-negative bacteria, with almost all A. baumannii isolates resistant to carbapenems (95.5%), and K. pneumoniae and P. aeruginosa showing carbapenem resistance rates of 59.5% and 34.6%, respectively. CONCLUSIONS: In hospitalised patients with severe COVID-19, secondary infections are considerably more common than co-infections, and are mostly due to Gram-negative bacterial pathogens showing a very high rate of antibiotic resistance.


Subject(s)
Anti-Bacterial Agents , Bacteremia , COVID-19 , Coinfection , Drug Resistance, Microbial , Fungemia , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteremia/complications , Bacteremia/drug therapy , Bacteremia/microbiology , COVID-19/complications , Coinfection/drug therapy , Coinfection/epidemiology , Coinfection/microbiology , Fungemia/complications , Fungemia/drug therapy , Fungemia/microbiology , Hospitalization/statistics & numerical data , Humans , Italy/epidemiology , Population Surveillance , Respiratory Tract Infections/complications , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology
2.
Medicina (Kaunas) ; 58(3)2022 Mar 17.
Article in English | MEDLINE | ID: covidwho-1753652

ABSTRACT

The general opinion in the literature is that these topics remain clearly understudied and underrated, with many unknown aspects and with controversial results in the respective areas of research. Based on the previous experience of our groups regarding such matters investigated separately, here we attempt a short overview upon their links. Thus, we summarize here the current state of knowledge regarding the connections between oxidative stress and: (a) orthopedic conditions; (b) COVID-19. We also present the reciprocal interferences among them. Oxidative stress is, of course, an interesting and continuously growing area, but what exactly is the impact of COVID-19 in orthopedic patients? In the current paper we also approached some theories on how oxidative stress, metabolism involvement, and even antibiotic resistance might be influenced by either orthopedic conditions or COVID-19. These manifestations could be relevant and of great interest in the context of this current global health threat; therefore, we summarize the current knowledge and/or the lack of sufficient evidence to support the interactions between these conditions.


Subject(s)
COVID-19 , Drug Resistance, Microbial , Global Health , Humans , Oxidative Stress
3.
Br J Gen Pract ; 72(714): 26-27, 2022 01.
Article in English | MEDLINE | ID: covidwho-1732292
4.
Eur J Hosp Pharm ; 29(2): 90-94, 2022 03.
Article in English | MEDLINE | ID: covidwho-1703505

ABSTRACT

AIMS AND OBJECTIVE: To compare antibiotic shortages in Europe between 2013 and 2020 and the views of hospital pharmacists on overcoming shortages via antimicrobial stewardship. METHODS: A series of European Association of Hospital Pharmacists (EAHP) surveys on medicine shortages, including a survey on the future crisis preparedness of hospital pharmacies, conducted between 2013 and 2020 were compared for the type of antibiotic shortages and respective mitigation strategy. These were analysed taking into account hospital pharmacists' views on antibiotics provided in the European Centre for Disease Prevention and Control (ECDC) survey on healthcare professionals' knowledge, attitudes and behaviours about antibiotics, antibiotic use and antibiotic resistance from 2018. RESULTS: Since 2013 there has frequently been a shortage of antibiotics in European hospitals. In 2014, 67% (347/521) of hospital pharmacists experienced shortages of antimicrobials compared with 77% (1032/1348) in 2018, 63% (1158/1837) in 2019 and 37% (539/1466) in 2020. More than 80% of hospital pharmacists managed antibiotic shortages through substitution in 2014 (284/336) and 2018 (786/946), while this percentage was 40% (63/158) and 42% (620/1466) in 2019 and 2020, respectively. Although 72% (870/1204) of hospital pharmacists received information on how to avoid inappropriate antibiotic prescribing, dispensing and administration, only 37% (450/1204) changed their views and 28% (338/1204) changed their practice in steering antimicrobial treatment. CONCLUSION: Antibiotic shortages affect proper antimicrobial stewardship because of limited appropriate alternatives, taking into account patients' clinical condition and type of infection. While substitution remains a leading mitigating tool for antibiotic shortages, it carries numerous risks and the potential for antimicrobial resistance and suboptimal health outcomes.


Subject(s)
Antimicrobial Stewardship , Pharmacists , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Microbial , Humans , Surveys and Questionnaires
5.
Int J Mol Sci ; 23(3)2022 Feb 08.
Article in English | MEDLINE | ID: covidwho-1686816

ABSTRACT

This Special Issue of the International Journal of Molecular Sciences, entitled "Antimicrobial Materials with Medical Applications", covers a selection of recent research and review articles in the field of antimicrobial materials, as well as their medical applications [...].


Subject(s)
Anti-Infective Agents/pharmacology , Disinfectants/pharmacology , Equipment Contamination/prevention & control , Drug Development , Drug Resistance, Microbial , Humans , Product Packaging
6.
J Antimicrob Chemother ; 77(2): 277-278, 2022 02 02.
Article in English | MEDLINE | ID: covidwho-1672216

ABSTRACT

COVID-19 has highlighted the worldwide inequities in access to the tools needed to tackle the pandemic. The same is the case for antibiotic resistance (ABR), which is projected to cause far greater devastation. The truth is that unless we tackle the burden of infectious diseases in low- and middle-income countries (LMICs), we will not impact ABR worldwide. Despite valiant efforts we have largely failed to address antibiotic conservation. We have directed millions of dollars into developing new antibiotics and surveillance systems and mostly ignored interventions such as infection prevention. Insufficient resources are dedicated to interventions such as sanitation and clean water, vaccination and changes in agricultural practice to reduce reliance on antimicrobials. Large-scale public health interventions are required. Funding mechanisms must be found to support LMICs in making these changes. Action is required at the highest levels.


Subject(s)
COVID-19 , Developing Countries , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Microbial , Humans , SARS-CoV-2
7.
Molecules ; 27(3)2022 Jan 18.
Article in English | MEDLINE | ID: covidwho-1625062

ABSTRACT

Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. Multidrug resistance may be also related to antimicrobial drugs, and is known to be one of the most serious global public health threats of this century. Indeed, this phenomenon has increased both mortality and morbidity as a consequence of treatment failures and its incidence in healthcare costs. The large amounts of antibiotics used in human therapies, as well as for farm animals and even for fishes in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. It is not negligible that the ongoing COVID-19 pandemic may further contribute to antimicrobial resistance. In this paper, multidrug resistance and antimicrobial resistance are underlined, focusing on the therapeutic options to overcome these obstacles in drug treatments. Lastly, some recent studies on nanodrug delivery systems have been reviewed since they may represent a significant approach for overcoming resistance.


Subject(s)
Drug Resistance, Multiple , Drug Resistance, Neoplasm , Animals , Drug Resistance, Microbial , Humans
8.
J Water Health ; 19(6): 895-906, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1606294

ABSTRACT

The continuous introduction of cleaning products containing benzalkonium chloride (BAC) from household discharges can mold the microbial communities in wastewater treatment plants (WWTPs) in a way still poorly understood. In this study, we performed an in vitro exposure of activated sludge from a WWTP in Costa Rica to BAC, quantified the changes in intI1, sul2, and qacE/qacEΔ1 gene profiles, and determined alterations in the bacterial community composition. The analysis of the qPCR data revealed elevated charges of antibiotic resistance genes in the microbial community; after BAC's exposure, a significant increase in the qacE/qacEΔ1 gene, which is related to ammonium quaternary resistance, was observed. The 16S rRNA gene sequences' analysis showed pronounced variations in the structure of the bacterial communities, including reduction of the alpha diversity values and an increase of the relative abundance of Alphaproteobacteria, particularly of Rhodospseudomonas and Rhodobacter. We confirmed that the microbial communities presented high resilience to BAC at the mg/mL concentration, probably due to constant exposure to this pollutant. They also presented antibiotic resistance-related genes with similar mechanisms to tolerate this substance. These mechanisms should be explored more thoroughly, especially in the context of high use of disinfectant.


Subject(s)
Benzalkonium Compounds , Sewage , Anti-Bacterial Agents/pharmacology , Bacteria/genetics , Benzalkonium Compounds/pharmacology , Drug Resistance, Microbial/genetics , Genes, Bacterial , RNA, Ribosomal, 16S/genetics , Waste Water
9.
Lancet Glob Health ; 10(2): e293-e297, 2022 02.
Article in English | MEDLINE | ID: covidwho-1573855

ABSTRACT

The COVID-19 pandemic has underlined the importance of an efficient and equitable supply of and access to essential health products. These factors are equally pertinent to the antimicrobial resistance pandemic, in which access to a portfolio of existing and pipeline antimicrobials plus complementary diagnostics is crucial. This Viewpoint focuses on market shaping in low-income and middle-income countries (LMICs), where the need for effective antimicrobials and complementary diagnostics is most acute. We propose the creation of a subscription and pooled procurement model that consolidates the growing demand for a portfolio of antimicrobials and diagnostics in LMICs. Anchored by regional market leaders, these pooling mechanisms would guarantee consistent private-sector and public-sector access in participating countries, while creating conditions for long-term best practice in stewardship. Supported by data from South Africa and India, this proposal sets out an innovative approach to tackle the antimicrobial resistance crisis in LMICs.


Subject(s)
Anti-Infective Agents/supply & distribution , COVID-19/epidemiology , Developing Countries , Diagnostic Tests, Routine , Anti-Infective Agents/economics , Drug Resistance, Microbial , Humans , Pandemics , Private Sector , Public Sector , SARS-CoV-2
10.
11.
Bioresour Technol ; 347: 126429, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1536445

ABSTRACT

Triclocarban (TCC) is in great market demand especially after the outbreak of COVID-19 pandemic, becoming an emerging pollutant. However, the impacts of TCC on the performance of nitrifying granular sludge system and the occurrence of antibiotic resistance genes (ARGs) were still unknown. This work explored the impacts of different concentrations of TCC on nitrifying granular sludge. Results showed that TCC suppressed the activities of ammonia-oxidizing microorganisms and decreased the abundance of Nitrospira. Adsorption was the main way for the removal of TCC and the biodegradation efficiency of TCC increased to 28.00% under 19.70 mg/L TCC addition. TCC enriched the ARGs and promoted the risks of their transferring in microorganisms. Pseudomonas might not only have strong resistance to TCC, but also propagate ARGs. The removal process of TCC and bacterial communities were important factors to promote the spread of ARGs. Thus, the existence of TCC presented a great environmental risk.


Subject(s)
COVID-19 , Microbiota , Anti-Bacterial Agents/pharmacology , Carbanilides , Drug Resistance, Microbial , Genes, Bacterial/genetics , Humans , Pandemics , SARS-CoV-2 , Sewage
12.
J Hazard Mater ; 425: 127774, 2022 03 05.
Article in English | MEDLINE | ID: covidwho-1517334

ABSTRACT

The demand for facial masks remains high. However, little is known about discarded masks as a potential refuge for contaminants and to facilitate enrichment and spread of antibiotic resistance genes (ARG) in the environment. We address this issue by conducting an in-situ time-series experiment to investigate the dynamic changes of ARGs, bacteria and protozoa associated with discarded masks. Masks were incubated in an estuary for 30 days. The relative abundance of ARGs in masks increased after day 7 but levelled off after 14 days. The absolute abundance of ARGs at 30 days was 1.29 × 1012 and 1.07 × 1012 copies for carbon and surgical masks, respectively. According to normalized stochasticity ratio analysis, the assembly of bacterial and protistan communities was determined by stochastic (NST = 62%) and deterministic (NST = 40%) processes respectively. A network analysis highlighted potential interactions between bacteria and protozoa, which was further confirmed by culture-dependent assays, that showed masks shelter and enrich microbial communities. An antibiotic susceptibility test suggested that antibiotic resistant pathogens co-exist within protozoa. This study provides an insight into the spread of ARGs through discarded masks and highlights the importance of managing discarded masks with the potential ecological risk of mask contamination.


Subject(s)
Anti-Bacterial Agents , COVID-19 , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Genes, Bacterial , Humans , Masks , Pandemics , SARS-CoV-2
13.
ACS Appl Mater Interfaces ; 13(46): 54706-54714, 2021 Nov 24.
Article in English | MEDLINE | ID: covidwho-1514382

ABSTRACT

Antimicrobial coatings are one method to reduce the spread of microbial diseases. Transparent coatings preserve the visual properties of surfaces and are strictly necessary for applications such as antimicrobial cell phone screens. This work describes transparent coatings that inactivate microbes within minutes. The coatings are based on a polydopamine (PDA) adhesive, which has the useful property that the monomer can be sprayed, and then the monomer polymerizes in a conformal film at room temperature. Two coatings are described (1) a coating where PDA is deposited first and then a thin layer of copper is grown on the PDA by electroless deposition (PDA/Cu) and (2) a coating where a suspension of Cu2O particles in a PDA solution is deposited in a single step (PDA/Cu2O). In the second coating, PDA menisci bind Cu2O particles to the solid surface. Both coatings are transparent and are highly efficient in inactivating microbes. PDA/Cu kills >99.99% of Pseudomonas aeruginosa and 99.18% of methicillin-resistant Staphylococcus aureus (MRSA) in only 10 min and inactivates 99.98% of SARS-CoV-2 virus in 1 h. PDA/Cu2O kills 99.94% of P. aeruginosa and 96.82% of MRSA within 10 min and inactivates 99.88% of SARS-CoV-2 in 1 h.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , Drug Resistance, Microbial/drug effects , SARS-CoV-2/drug effects , COVID-19/virology , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Pseudomonas aeruginosa/drug effects , Surface Properties
14.
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
15.
Antimicrob Agents Chemother ; 65(7): e0001321, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1476381

ABSTRACT

The SOS response to DNA damage is a conserved stress response in Gram-negative and Gram-positive bacteria. Although this pathway has been studied for years, its relevance is still not familiar to many working in the fields of clinical antibiotic resistance and stewardship. Under some conditions, the SOS response favors DNA repair and preserves the genetic integrity of the organism. On the other hand, the SOS response also includes induction of error-prone DNA polymerases, which can increase the rate of mutation, called the mutator phenotype or "hypermutation." As a result, mutations can occur in genes conferring antibiotic resistance, increasing the acquisition of resistance to antibiotics. Almost all of the work on the SOS response has been on bacteria exposed to stressors in vitro. In this study, we sought to quantitate the effects of SOS-inducing drugs in vivo, in comparison with the same drugs in vitro. We used a rabbit model of intestinal infection with enteropathogenic Escherichia coli strain E22. SOS-inducing drugs triggered the mutator phenotype response in vivo as well as in vitro. Exposure of E. coli strain E22 to ciprofloxacin or zidovudine, both of which induce the SOS response in vitro, resulted in increased antibiotic resistance to 3 antibiotics: rifampin, minocycline, and fosfomycin. Zinc was able to inhibit the SOS-induced emergence of antibiotic resistance in vivo, as previously observed in vitro. Our findings may have relevance in reducing the emergence of resistance to new antimicrobial drugs.


Subject(s)
Escherichia coli , SOS Response, Genetics , Animals , Anti-Bacterial Agents/pharmacology , Ciprofloxacin/pharmacology , Drug Resistance, Microbial , Escherichia coli/genetics , Mutation , Rabbits
16.
Molecules ; 26(19)2021 Oct 04.
Article in English | MEDLINE | ID: covidwho-1463767

ABSTRACT

Antimicrobial resistance was one of the top priorities for global public health before the start of the 2019 coronavirus pandemic (COVID-19). Moreover, in this changing medical landscape due to COVID-19, finding new organic structures with antimicrobial and antiviral properties is a priority in current research. The Biginelli synthesis that mediates the production of pyrimidine compounds has been intensively studied in recent decades, especially due to the therapeutic properties of the resulting compounds, such as calcium channel blockers, anticancer, antiviral, antimicrobial, anti-inflammatory or antioxidant compounds. In this review we aim to review the Biginelli syntheses reported recently in the literature that mediates the synthesis of antimicrobial compounds, the spectrum of their medicinal properties, and the structure-activity relationship in the studied compounds.


Subject(s)
Anti-Infective Agents/chemical synthesis , Pyrimidines/chemical synthesis , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Chemistry Techniques, Synthetic/methods , Drug Discovery , Drug Resistance, Microbial , Humans , Models, Molecular , Pyrimidines/chemistry , Pyrimidines/pharmacology , SARS-CoV-2/drug effects
17.
Pan Afr Med J ; 40: 12, 2021.
Article in English | MEDLINE | ID: covidwho-1458484

ABSTRACT

The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a new virus that is responsible for COVID-19, a disease that complicate health conditions and results in death. The total diversion of attention of government and health care workers (HCWs) to prevent the escalation of the pandemic disease has placed a great barrier to diagnosis and treatment of other illnesses that share common symptoms with COVID-19, and that has consequently enabled the endemic practice of self-antimicrobial medication to increase in Nigeria. Development of secondary infections in COVID-19 and in other conditions, caused by antibiotic resistant pathogens could make them more deadly now or in the future. The mitigation strategies adopted in Nigeria and its States, which include enforcing social distancing, partial or total lockdown, and restricting access to health care facilities for non COVID-19 patients, have further increased the demand of antimicrobial agents from unauthorized outlets in communities for inappropriate use. A cross-sectional survey of 162 randomly selected individuals that visited medical stores and 170 medical store owners to evaluates the level of self-medication with five oral broad spectrum antibiotics and antimalaria during the lockdown revealed an increase (68.5%) in practice of self-medication with at least one of the antimicrobial and emergence of new abusers. Blind treatment of symptoms of malaria and common cold without diagnosis and health care consultation was nearly 100%. Irrational use of sanitizers, disinfectants and other cidal agents that can fuel antimicrobial resistance has drastically increased in communities. Exposure of microorganisms in the environment without caution to large volume of fumigants is increasing on daily basis. We strongly recommend that while mitigating SARS-CoV-2 virus spread, efficacious and feasible technological, social, economic and behavioral interventions that will also control the evolution and spread antimicrobial resistant microorganisms should be applied.


Subject(s)
Anti-Bacterial Agents/therapeutic use , COVID-19/prevention & control , Communicable Disease Control , Drug Resistance, Microbial , Pandemics/prevention & control , Self Medication , COVID-19/epidemiology , Health Services Accessibility , Humans , Nigeria/epidemiology , Physical Distancing , SARS-CoV-2 , Self Medication/adverse effects
18.
J Laryngol Otol ; 135(10): 855-857, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1434031

ABSTRACT

OBJECTIVE: Recurrent acute otitis media is common in children. The preferred treatment measures for recurrent acute otitis media have a mixed evidence base. This study sought to assess baseline practice across ENT departments in England. METHODS: A national telephone survey of healthcare staff was conducted. Every ENT centre in England was contacted. A telephone script was used to ask about antibiotic and grommet use and duration in recurrent acute otitis media cases. RESULTS: Ninety-six centres (74 per cent) provided complete information. Recurrent acute otitis media treatment across England by ENT departments varied. The antibiotic first- and second-line prophylaxis offered varies, with trimethoprim used in 33 centres and 29 centres not offering any antibiotics. The timing or choice about when to use grommets also varies, but 87 centres (91 per cent) offer grommet surgery at one stage. CONCLUSION: The treatments received by children in England for recurrent acute otitis media vary by centre; collaborative research in this area is advised.


Subject(s)
Middle Ear Ventilation/statistics & numerical data , Otitis Media/drug therapy , Otolaryngology/statistics & numerical data , Surveys and Questionnaires/standards , Acute Disease , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents, Urinary/administration & dosage , Anti-Infective Agents, Urinary/therapeutic use , Child , Drug Resistance, Microbial , England/epidemiology , Humans , Middle Ear Ventilation/methods , Otitis Media/surgery , Otolaryngology/organization & administration , Personal Health Services/statistics & numerical data , Recurrence , State Medicine/organization & administration , Surveys and Questionnaires/statistics & numerical data , Trimethoprim/administration & dosage , Trimethoprim/therapeutic use
19.
PLoS Pathog ; 17(9): e1009929, 2021 09.
Article in English | MEDLINE | ID: covidwho-1430555

ABSTRACT

Remdesivir (RDV), a broadly acting nucleoside analogue, is the only FDA approved small molecule antiviral for the treatment of COVID-19 patients. To date, there are no reports identifying SARS-CoV-2 RDV resistance in patients, animal models or in vitro. Here, we selected drug-resistant viral populations by serially passaging SARS-CoV-2 in vitro in the presence of RDV. Using high throughput sequencing, we identified a single mutation in RNA-dependent RNA polymerase (NSP12) at a residue conserved among all coronaviruses in two independently evolved populations displaying decreased RDV sensitivity. Introduction of the NSP12 E802D mutation into our SARS-CoV-2 reverse genetics backbone confirmed its role in decreasing RDV sensitivity in vitro. Substitution of E802 did not affect viral replication or activity of an alternate nucleoside analogue (EIDD2801) but did affect virus fitness in a competition assay. Analysis of the globally circulating SARS-CoV-2 variants (>800,000 sequences) showed no evidence of widespread transmission of RDV-resistant mutants. Surprisingly, we observed an excess of substitutions in spike at corresponding sites identified in the emerging SARS-CoV-2 variants of concern (i.e., H69, E484, N501, H655) indicating that they can arise in vitro in the absence of immune selection. The identification and characterisation of a drug resistant signature within the SARS-CoV-2 genome has implications for clinical management and virus surveillance.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , COVID-19 , Coronavirus RNA-Dependent RNA Polymerase/genetics , Drug Resistance, Microbial/genetics , SARS-CoV-2/drug effects , Adenosine Monophosphate/pharmacology , Alanine/pharmacology , Animals , Biological Evolution , COVID-19/drug therapy , Chlorocebus aethiops , Humans , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
20.
J Hazard Mater ; 423(Pt B): 127152, 2022 02 05.
Article in English | MEDLINE | ID: covidwho-1401614

ABSTRACT

Chlorine disinfection is a key global public health strategy for the prevention and control of diseases, such as COVID-19. However, little is known about effects of low levels of residual chlorine on freshwater microbial communities and antibiotic resistomes. Here, we treated freshwater microcosms with continuous low concentrations of chlorine and quantified the effects on aquatic and zebrafish intestinal microbial communities and antibiotic resistomes, using shotgun metagenome and 16S rRNA gene sequencing. Although chlorine rapidly degraded, it altered the aquatic microbial community composition over time and disrupted interactions among microbes, leading to decreases in community complexity and stability. However, community diversity was unaffected. The majority of ecological functions, particularly metabolic capacities, recovered after treatment with chlorine for 14 d, due to microbial community redundancy. There were also increased levels of antibiotic-resistance gene dissemination by horizontal and vertical gene transfer under chlorine treatment. Although the zebrafish intestinal microbial community recovered from temporary dysbiosis, growth and behavior of zebrafish adults were negatively affected by chlorine. Overall, our findings demonstrate the negative effects of residual chlorine on freshwater ecosystems and highlight a possible long-term risk to public health.


Subject(s)
COVID-19 , Microbiota , Animals , Chlorine/toxicity , Drug Resistance, Microbial , Fresh Water , RNA, Ribosomal, 16S/genetics , SARS-CoV-2 , Zebrafish
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