The Effects of COVID-19 on Antifungal Prescribing in the UK-Lessons to Learn.

Fungal infections are increasingly prevalent; however, antifungal stewardship attracts little funding or attention. Previous studies have shown that knowledge of guidelines and scientific evidence regarding antifungals is poor, leading to prescribing based on personal experiences and the inherent biases this entails. We carried out a retrospective study of inpatient antifungal usage at two major hospitals.

Rising incidence of Pneumocystis pneumonia: A population-level descriptive ecological study in England.

Objectives: Pneumocystis pneumonia (PCP) is an opportunistic infection that causes significant morbidity and mortality in the immunocompromised population. This population is growing and diversifying, yet contemporary epidemiology is lacking. We investigated the population-level incidence of PCP over the past decade.

Characterisation of SARS-CoV-2 genomic variation in response to molnupiravir treatment in the AGILE Phase IIa clinical trial.

Molnupiravir is an antiviral, currently approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) for treating at-risk COVID-19 patients, that induces lethal error catastrophe in SARS-CoV-2. How this drug-induced mechanism of action might impact the emergence of resistance mutations is unclear. To investigate this, we used samples from the AGILE Candidate Specific Trial (CST)-2 (clinical trial number NCT04746183).

Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial.

Background: The antiviral drug molnupiravir was licensed for treating at-risk patients with COVID-19 on the basis of data from unvaccinated adults. We aimed to evaluate the safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals with COVID-19.

Methods: This randomised, placebo-controlled, double-blind, phase 2 trial (AGILE CST-2) was done at five National Institute for Health and Care Research sites in the UK.

Pneumolysin suppresses the initial macrophage pro-inflammatory response to Streptococcus pneumoniae.

Published data for the Streptococcus pneumoniae virulence factor Pneumolysin (Ply) show contradictory effects on the host inflammatory response to infection. Ply has been shown to activate the inflammasome, but also can bind to MRC-1 resulting in suppression of dendritic cell inflammatory responses. We have used an in vitro infection model of human monocyte-derived macrophages (MDM), and a mouse model of pneumonia to clarify whether pro- or anti-inflammatory effects dominate the effects of Ply on the initial macrophage inflammatory response to S.

Inpatient COVID-19 mortality has reduced over time: Results from an observational cohort.

Background: The Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes for those admitted with severe Covid were different in the first and second waves.

Methods: The study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and March 2021, who tested positive for Covid-19 by PCR within 3-days of admissions.

Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia.

Background: A standardised approach to assessing COVID-19 survivors has not been established, largely due to the paucity of data on medium- and long-term sequelae. Interval chest radiography is recommended following community-acquired pneumonia; however, its utility in monitoring recovery from COVID-19 pneumonia remains unclear.

Methods: This was a prospective single-centre observational cohort study.

Hospital Mortality and Resource Implications of Hospitalisation with COVID-19 in London, UK: A Prospective Cohort Study.

Background: Coronavirus disease 2019 (COVID-19) had a significant impact on the National Health Service in the United Kingdom (UK), with over 35 000 cases reported in London by July 30, 2020. Detailed hospital-level information on patient characteristics, outcomes, and capacity strain is currently scarce but would guide clinical decision-making and inform prioritisation and planning.

Methods: We aimed to determine factors associated with hospital mortality and describe hospital and ICU strain by conducting a prospective cohort study at a tertiary academic centre in London, UK.

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report.

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement.

The perils of a persistent cough.

http://bit.ly/3aBTQip.

Opportunistic bacterial, viral and fungal infections of the lung.

Opportunistic infections are a major cause of morbidity and mortality in severely immunocompromised patients, such as those given chemotherapy or biological therapies, and those with haematological malignancy, aplastic anaemia or HIV infection, or recipients of solid organ or stem cell transplants. The type and degree of immune defect dictates the profile of potential opportunistic pathogens; T-cell-mediated defects increase the risk of viral (cytomegalovirus, respiratory viruses) and infections, whereas neutrophil defects are associated with bacterial pneumonia and invasive aspergillosis. However, patients often have combinations of immune defects, and a wide range of other opportunistic infections can cause pneumonia.

Relative Contributions of Extracellular and Internalized Bacteria to Early Macrophage Proinflammatory Responses to Streptococcus pneumoniae.

Both intracellular immune sensing and extracellular innate immune sensing have been implicated in initiating macrophage proinflammatory cytokine responses to The capsule, a major virulence determinant, prevents phagocytosis, and we hypothesized that this would reduce activation of host innate inflammatory responses by preventing activation of intracellular proinflammatory signaling pathways. We investigated this hypothesis in human monocyte-derived macrophages stimulated with encapsulated or isogenic unencapsulated mutant Unexpectedly, despite strongly inhibiting bacterial internalization, the capsule resulted in enhanced inflammatory cytokine production by macrophages infected with Experiments using purified capsule material and a mutant expressing an serotype 4 capsule indicated these differences required whole bacteria and were not due to proinflammatory effects of the capsule itself. Transcriptional profiling demonstrated relatively few differences in macrophage gene expression profiles between infections with encapsulated and those with unencapsulated , largely limited to reduced expression of proinflammatory genes in response to unencapsulated bacteria, predicted to be due to reduced activation of the NF-κB family of transcription factors.

A Prospective Real-World Study of the Impact of an Antifungal Stewardship Program in a Tertiary Respiratory-Medicine Setting.

There has been an increase in fungal infections in patients with chronic lung disease over the past decades, which is associated with rapidly increasing costs to health care systems. An antifungal stewardship team was introduced to a tertiary cardiopulmonary hospital, consisting of a medical mycologist and pharmacy support providing weekly stewardship ward rounds, twice-monthly multidisciplinary team meetings, and a dedicated weekly outpatient clinic. A database was set up to record the activity of the stewardship team.

A Quorum-Sensing System That Regulates Biofilm Formation and Surface Polysaccharide Production.

Despite vaccines, kills more than a million people yearly. Thus, understanding how pneumococci transition from commensals to pathogens is particularly relevant. Quorum sensing regulates collective behaviors and thus represents a potential driver of commensal-to-pathogen transitions.

Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae.

Background: Welders are at increased risk of pneumococcal pneumonia. The mechanism for this association is not known. The capacity of pneumococci to adhere to and infect lower airway cells is mediated by host-expressed platelet-activating factor receptor (PAFR).

Community-acquired pneumonia.

Purpose Of Review: Community-acquired pneumonia (CAP) is the most common infectious disease cause of death. We summarize recent findings regarding the epidemiology of CAP in adults, efficacy of vaccines against Streptococcus pneumoniae, diagnostics, and discuss the current controversy between CAP and healthcare-associated pneumonia (HCAP).

Recent Findings: The emergence of the Middle East respiratory syndrome coronavirus and the avian influenza A strain H7N9 are of concern but still these are infrequent causes of CAP.

TLR-mediated inflammatory responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial lipoproteins.

Streptococcus pneumoniae infections induce inflammatory responses that contribute toward both disease pathogenesis and immunity, but the host-pathogen interactions that mediate these effects are poorly defined. We used the surface lipoprotein-deficient ∆lgt pneumococcal mutant strain to test the hypothesis that lipoproteins are key determinants of TLR-mediated immune responses to S. pneumoniae.

Protective role of the capsule and impact of serotype 4 switching on Streptococcus mitis.

The polysaccharide capsule surrounding Streptococcus pneumoniae is essential for virulence. Recently, Streptococcus mitis, a human commensal and a close relative of S. pneumoniae, was also shown to have a capsule.