JAC Antimicrob Resist
December 2024
Background: The impact of antimicrobial resistance (AMR) on death at the patient level is challenging to estimate. We aimed to characterize AMR-attributable deaths in a large UK teaching hospital.
Methods: This retrospective study investigated all deceased patients in 2022.
HIV causes susceptibility to respiratory pathogens, including tuberculosis (TB), but the underlying immunological mechanisms remain incompletely understood. We obtained whole blood and bronchoalveolar lavage (BAL) from TB-exposed people in the presence or absence of antiretroviral-naïve HIV co-infection. Bulk transcriptional profiling demonstrated compartment-specific enrichment of immunological processes.
View Article and Find Full Text PDFTuberculosis is a major global health problem and is one of the top 10 causes of death worldwide. There is a pressing need for new treatments that circumvent emerging antibiotic resistance. parasitises macrophages, reprogramming them to establish a niche in which to proliferate, therefore macrophage manipulation is a potential host-directed therapy if druggable molecular targets could be identified.
View Article and Find Full Text PDFBackground: Tuberculosis (TB) can induce secondary hemophagocytic lymphohistiocytosis (HLH), a severe inflammatory syndrome with high mortality. We integrated all published reports of adult HIV-negative TB-associated HLH (TB-HLH) to define clinical characteristics, diagnostic strategies, and therapeutic approaches associated with improved survival.
Methods: PubMed, Embase, and Global Index Medicus were searched for eligible records.
Mechanisms by which HIV causes susceptibility to respiratory pathogens remain incompletely understood. We obtained whole blood and bronchoalveolar lavage (BAL) from people with latent TB infection in the presence or absence of antiretroviral-naïve HIV co-infection. Transcriptomic and flow cytometric analyses demonstrated HIV-associated cell proliferation plus type I interferon activity in blood and effector memory CD8 T-cells in BAL.
View Article and Find Full Text PDFObjectives: To assess the performance of T2Candida for the diagnosis of invasive candidiasis (IC) against gold standards of candidaemia or consensus IC definitions, and to evaluate the impact of T2Candida on antifungal drug prescribing.
Methods: A retrospective review was undertaken of all T2Candida (T2MR technology, T2 Biosystems) performed from October 2020 to February 2022. T2Candida performance was evaluated against confirmed candidaemia or against proven/probable IC within 48 hours of T2Candida, and its impact on antifungal drug prescriptions.
IL-6 responses are ubiquitous in () infections, but their role in determining human tuberculosis (TB) disease risk is unknown. We used single nucleotide polymorphisms (SNPs) in and near the IL-6 receptor () gene, focusing on the non-synonymous variant, rs2228145, associated with reduced classical IL-6 signalling, to assess the effect of altered IL-6 activity on TB disease risk. We identified 16 genome wide association studies (GWAS) of TB disease collating 17,982 cases of TB disease and 972,389 controls across 4 continents.
View Article and Find Full Text PDFBackground: A low procalcitonin (PCT) concentration facilitates exclusion of bacterial co-infections in COVID-19, but high costs associated with PCT measurements preclude universal adoption. Changes in inflammatory markers, including C-reactive protein (CRP), can be concordant, and predicting low PCT concentrations may avoid costs of redundant tests and support more cost-effective deployment of this diagnostic biomarker.
Objectives: To explore whether, in COVID-19, low PCT values could be predicted by the presence of low CRP concentrations.
Background: We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.
Methods: We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew's Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work.
Host immune responses at the site of infection can mediate pathogenesis of tuberculosis (TB) and onward transmission of infection. We hypothesized that pathological immune responses would be enriched at the site of host-pathogen interactions modeled by a standardized tuberculin skin test (TST) challenge in patients with active TB compared to those without disease, and interrogated immune responses by genome-wide transcriptional profiling. We show exaggerated interleukin-17A (IL-17A) and T helper 17 (T17) responses among 48 individuals with active TB compared to 191 with latent TB infection, associated with increased neutrophil recruitment and matrix metalloproteinase-1 expression, both involved in TB pathogenesis.
View Article and Find Full Text PDFObjective: In people living with HIV (PLHIV), we sought to test the hypothesis that long term anti-retroviral therapy restores the normal T cell repertoire, and investigate the functional relationship of residual repertoire abnormalities to persistent immune system dysregulation.
Methods: We conducted a case-control study in PLHIV and HIV-negative volunteers, of circulating T cell receptor repertoires and whole blood transcriptomes by RNA sequencing, complemented by metadata from routinely collected health care records.
Results: T cell receptor sequencing revealed persistent abnormalities in the clonal T cell repertoire of PLHIV, characterized by reduced repertoire diversity and oligoclonal T cell expansion correlated with elevated CD8 T cell counts.
Background: COVID-19 is infrequently complicated by bacterial co-infection, but antibiotic prescriptions are common. We used community-acquired pneumonia (CAP) as a benchmark to define the processes that occur in bacterial pulmonary infections, testing the hypothesis that baseline inflammatory markers and their response to antibiotic therapy could distinguish bacterial co-infection from COVID-19.
Methods: Retrospective cohort study of CAP (lobar consolidation on chest radiograph) and COVID-19 (PCR detection of SARS-CoV-2) patients admitted to Royal Free Hospital (RFH) and Barnet Hospital (BH), serving as independent discovery and validation cohorts.
Dysregulated IL-1β and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokines are urgently needed to complement clinical trials of therapeutic targeting of IL-1β and IL-6 in COVID-19. We show that the expression of IL-1β or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis.
View Article and Find Full Text PDFDysregulated IL-1β and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokines are urgently needed to complement clinical trials of therapeutic targeting of IL-1β and IL-6 in COVID-19. We show that the expression of IL-1β or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis.
View Article and Find Full Text PDFIntroduction: Ageing is associated with increased number of infections, decreased vaccine efficacy and increased systemic inflammation termed inflammageing. These changes are reflected by reduced recall responses to varicella zoster virus (VZV) challenge in the skin of older adults. Vitamin D deficiency is more common in the old and has been associated with frailty and increased inflammation.
View Article and Find Full Text PDFThe outbreak of COVID-19 in the UK in March 2020 required a radical remodelling of the medical workforce at Royal Free London NHS Foundation Trust to prepare for the anticipated surge of hospital admissions. The provision of relevant teaching and training was immediately identified as a priority, particularly for staff due to work outside their regular medical specialty. Rather than deliver face-to-face teaching, doctors at the Trust utilised Microsoft Teams, an online communications and collaboration platform, to deliver a multi-disciplinary Trust-wide education programme responsive to the needs of surveyed medical staff.
View Article and Find Full Text PDFThe emergence of the novel beta coronavirus SARS-CoV-2 and the ensuing COVID-19 pandemic has generated a rapidly evolving research landscape in the search for new therapeutic agents. The intravenous antiviral drug remdesivir has activity against SARS-CoV-2 and now studies have reported its clinical efficacy, demonstrating shorter time to recovery in hospitalised patients with severe COVID-19. Adverse event rates were low and remdesivir has now received conditional marketing authorisation from the European Medicines Agency.
View Article and Find Full Text PDFTeicoplanin possesses several convenient properties for use in the delivery of outpatient parenteral antimicrobial therapy (OPAT) services. However, its use is not widespread and data on its efficacy in the OPAT setting are limited. Here we present a case series of patients undergoing OPAT care being treated by either teicoplanin-based (n = 107) or ceftriaxone-based (n = 191) antibiotic regimens.
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