Towards the sustainable discovery and development of new antibiotics

Nature Reviews Chemistry, Journal Year: 2021, Volume and Issue: 5(10), P. 726 - 749

Published: Aug. 19, 2021

An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast current level investment their development, particularly fields natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry modes action are desperately needed worldwide tackle public health menace posed antimicrobial resistance. Here, our consortium presents a strategic blueprint substantially improve ability discover develop new antibiotics. We propose both short-term long-term solutions overcome most urgent limitations various sectors research funding, aiming bridge gap between academic, industrial political stakeholders, unite interdisciplinary expertise order efficiently fuel translational pipeline benefit future generations.

Language: Английский

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The role of co-infections and secondary infections in patients with COVID-19

Pneumonia, Journal Year: 2021, Volume and Issue: 13(1)

Published: April 24, 2021

Abstract Background It has been recognised for a considerable time-period, that viral respiratory infections predispose patients to bacterial infections, and these co-infections have worse outcome than either infection on its own. However, it is still unclear what exact roles and/or superinfections play in with COVID-19 infection. Main body This was an extensive review of the current literature regarding SARS-CoV-2 The definitions used were those Centers Disease Control Prevention (US), which defines coinfection as one occurring concurrently initial infection, while are follow previous especially when caused by microorganisms resistant, or become antibiotics earlier. Some researchers envisioned three potential scenarios bacterial/SARS-CoV-2 co-infection; namely, secondary following colonisation, combined viral/bacterial pneumonia, superinfection SARS-CoV-2. There myriad published articles ranging from letters editor systematic reviews meta-analyses describing varying ranges co-infection COVID-19. concomitant described included other viruses, bacteria, including mycobacteria, fungi, well other, more unusual, pathogens. will be seen this review, there often not clear distinction made authors referring to, whether true concomitant/co-infections superinfections. In addition, possible mechanisms interactions between SARS-CoV-2, particularly discussed further. Lastly, impact severity their also described. Conclusion describes rates although two literature. When they occur, appear associated both poorer outcomes.

Language: Английский

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Neuroimaging manifestations in children with SARS-CoV-2 infection: a multinational, multicentre collaborative study

The Lancet Child & Adolescent Health, Journal Year: 2020, Volume and Issue: 5(3), P. 167 - 177

Published: Dec. 17, 2020

Language: Английский

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Viral Respiratory Pathogens and Lung Injury

Clinical Microbiology Reviews, Journal Year: 2021, Volume and Issue: 34(3)

Published: April 6, 2021

Several viruses target the human respiratory tract, causing different clinical manifestations spanning from mild upper airway involvement to life-threatening acute distress syndrome (ARDS). As dramatically evident in ongoing SARS-CoV-2 pandemic, picture is not always easily predictable due combined effect of direct viral and indirect patient-specific immune-mediated damage.

Language: Английский

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Coinfections with Other Respiratory Pathogens among Patients with COVID-19

Microbiology Spectrum, Journal Year: 2021, Volume and Issue: 9(1)

Published: July 21, 2021

Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are at an increased risk for coinfections; therefore, physicians need to be cognizant about excluding other treatable pathogens. Here, we report coinfection with SARS-CoV-2 and pathogens in patients admitted the disease (COVID) care facilities of Indian tertiary hospital. From June 2020 through January 2021, tested 191 33 using fast track diagnostics pathogen (FTD-33) assay. Additionally, information regarding relevant was collected by reviewing their laboratory data. Overall, 13 were identified among infected SARS-CoV-2, 46.6% (89/191) had one or more additional Bacterial coinfections (41.4% [79/191]) frequent, Staphylococcus aureus being most common, followed Klebsiella pneumoniae. Coinfections Pneumocystis jirovecii Legionella pneumophila also identified. The viral rate 7.3%, human adenovirus rhinovirus common. Five our cohort positive cultures Acinetobacter baumannii K. pneumoniae, two active Mycobacterium tuberculosis infection. In total, 47.1% (90/191) higher proportion supports systemic use antibiotics pneumonia rapid de-escalation based on PCR/culture results. timely simultaneous identification can contribute improved health COVID-19 enhanced antibiotic stewardship during pandemic. IMPORTANCE may worsen outcomes further investigation. We found a coinfected A better understanding prevalence profile effective patient management current

Language: Английский

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Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study

Frontiers in Microbiology, Journal Year: 2021, Volume and Issue: 12

Published: June 23, 2021

The human oral microbiome (HOM) is the second largest microbial community after gut and can impact onset progression of several localized systemic diseases, including those viral origin, especially for viruses entering body via oropharynx. However, this important aspect has not been clarified new pandemic coronavirus SARS-CoV-2, causing COVID-19 disease, despite it being one many respiratory having oropharynx as primary site replication. In particular, no data are available about non-bacterial components HOM (fungi, viruses), which instead shown to be crucial other diseases. Consistent with this, study aimed define in patients, evidence any association between its profile clinical disease. Seventy-five rinse samples were analyzed by Whole Genome Sequencing (WGS) simultaneously identify bacteria, fungi, viruses. To correlate local virus replication, SARS-CoV-2 amount cavity was quantified digital droplet PCR. Moreover, inflammation secretory immune response also assessed, respectively measuring release pro-inflammatory cytokines (L-6, IL-17, TNFα, GM-CSF) production immunoglobulins A (sIgA). results showed presence dysbiosis patients compared matched controls, significantly decreased alpha-diversity value lower species richness subjects. Notably, correlated symptom severity ( p = 0.006), increased < 0.01). parallel, a mucosal sIgA observed more severely symptomatic 0.02), suggesting that early control infection correct development influenced profile. conclusion, presented here suggest may defining individual susceptibility infection, facilitating or rather, inducing protective IgA response. Although possible determine whether alteration cause effect these parameters considered markers personalized therapy vaccine development.

Language: Английский

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Increasing Consumption of Antibiotics during the COVID-19 Pandemic: Implications for Patient Health and Emerging Anti-Microbial Resistance

Antibiotics, Journal Year: 2022, Volume and Issue: 12(1), P. 45 - 45

Published: Dec. 28, 2022

The emergence of COVID-19 infection led to the indiscriminate use antimicrobials without knowing their efficacy in treating disease. gratuitous antibiotics for treatment raises concerns about antimicrobial resistance (AMR). In this systematic review, we performed a thorough search using Preferred Reporting Items Systematic Reviews and Meta-Analyses (PRISMA) guidelines scientific databases (Scopus, Web Science, PubMed) identify studies where were prescribed treat (December 2019 December 2021). Of 970 identified studies, 130 included our analyses. Almost 78% patients have been an antibiotic. Cephalosporins most (30.1% patients) antibiotics, followed by azithromycin (26% patients). Antibiotics regardless reported severity; overall rate antibiotic was similar when comparing with severe or critical illness (77.4%) mild moderate (76.8%). Secondary infections mentioned only 11 studies. We conclude that related lack strategy overuse proper clinical rationale. Based on findings, propose stewardship should be retained as priority while viral pandemics.

Language: Английский

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Graphene-based flexible wearable sensors: mechanisms, challenges, and future directions

The International Journal of Advanced Manufacturing Technology, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 17, 2023

Language: Английский

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Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 2108 - 2108

Published: Feb. 20, 2021

Severe COVID-19 is characterized by a "cytokine storm", the mechanism of which not yet understood. I propose that cytokine storms result from synergistic interactions among Toll-like receptors (TLR) and nucleotide-binding oligomerization domain-like (NLR) due to combined infections SARS-CoV-2 with other microbes, mainly bacterial fungal. This proposition based on eight linked types evidence their logical connections. (1) cases differ healthy controls mild patients in exhibiting increased TLR4, TLR7, TLR9 NLRP3 activity. (2) related coronaviruses activate TLR3, RIG1 NLRP3. (3) cannot, therefore, account for innate receptor activation pattern (IRAP) found severe patients. (4) also differs its form being fungal infections. (5) Respiratory TLR2, (6) A combination bacterial/fungal coinfections accounts IRAP why it cases. (7) Notably, TLR7 (viral) TLR4 (bacterial/fungal) synergize, (both bacterial/fungal) synergize TLR2 (viral bacterial). (8) Thus, SARS-CoV-2-bacterium/fungus coinfection produces activation, resulting hyperinflammation characteristic storm. Unique clinical, experimental therapeutic predictions (such as melatonin effective treating COVID-19) are discussed, broader implications outlined understanding syndromes such acute lung injury, respiratory distress syndrome sepsis display varied storm symptoms.

Language: Английский

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Microbial co-infections in COVID-19: Associated microbiota and underlying mechanisms of pathogenesis

Microbial Pathogenesis, Journal Year: 2021, Volume and Issue: 156, P. 104941 - 104941

Published: May 4, 2021

Language: Английский

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