Investigating the time to blood culture positivity: why does it take so long?

Bloodstream infections (BSIs) are one of the most serious infections investigated by microbiologists. However, the time to detect a BSI fails to meet the rapidity required to inform clinical decisions in real time. Blood culture (BC) is considered the gold standard for diagnosing bloodstream infections.

Application of Pathogen Genomics to Outbreak Investigation.

Outbreaks are a risk to public health particularly when pathogenic, hypervirulent, and/or multidrug-resistant organisms (MDROs) are involved. In a hospital setting, vulnerable populations such as the immunosuppressed, intensive care patients, and neonates are most at risk. Rapid and accurate outbreak detection is essential to implement effective interventions in clinical areas to control and stop further transmission.

Community antibiotic prescribing in patients with COVID-19 across three pandemic waves: a population-based study in Scotland, UK.

Objectives: This study aims to examine community antibiotic prescribing across a complete geographical area for people with a positive COVID-19 test across three pandemic waves, and to examine health and demographic factors associated with antibiotic prescribing.

Design: A population-based study using administrative data.

Setting: A complete geographical region within Scotland, UK.

Rapid determination of antimicrobial susceptibility of Gram-negative bacteria from clinical blood cultures using a scattered light-integrated collection device.

A bloodstream infection (BSI) presents a complex and serious health problem, a problem that is being exacerbated by increasing antimicrobial resistance (AMR). The current turnaround times (TATs) for most antimicrobial susceptibility testing (AST) methods offer results retrospective of treatment decisions, and this limits the impact AST can have on antibiotic prescribing and patient care. Progress must be made towards rapid BSI diagnosis and AST to improve antimicrobial stewardship and reduce preventable deaths from BSIs.

Repurposing Mitomycin C in Combination with Pentamidine or Gentamicin to Treat Infections with Multi-Drug-Resistant (MDR) .

The aims of this study were (i) to determine if the combination of mitomycin C with pentamidine or existing antibiotics resulted in enhanced efficacy versus infections with MDR in vivo; and (ii) to determine if the doses of mitomycin C and pentamidine in combination can be reduced to levels that are non-toxic in humans but still retain antibacterial activity. Resistant clinical isolates of , a mutant strain over-expressing the MexAB-OprM resistance nodulation division (RND) efflux pump and a strain with three RND pumps deleted, were used. MIC assays indicated that all strains were sensitive to mitomycin C, but deletion of three RND pumps resulted in hypersensitivity and over-expression of MexAB-OprM caused some resistance.

Modulation of multidrug-resistant clone success in Escherichia coli populations: a longitudinal, multi-country, genomic and antibiotic usage cohort study.

Background: The effect of antibiotic usage on the success of multidrug-resistant (MDR) clones in a population remains unclear. With this genomics-based molecular epidemiology study, we aimed to investigate the contribution of antibiotic use to Escherichia coli clone success, relative to intra-strain competition for colonisation and infection.

Methods: We sequenced all the available E coli bloodstream infection isolates provided by the British Society for Antimicrobial Chemotherapy (BSAC) from 2012 to 2017 (n=718) and combined these with published data from the UK (2001-11; n=1090) and Norway (2002-17; n=3254).

Combination Therapy with Ciprofloxacin and Pentamidine against Multidrug-Resistant : Assessment of In Vitro and In Vivo Efficacy and the Role of Resistance-Nodulation-Division (RND) Efflux Pumps.

The aim of this work was to (i) evaluate the efficacy of a combination treatment of pentamidine with ciprofloxacin against larvae infected with an MDR strain of and (ii) determine if pentamidine acts as an efflux-pump inhibitor. Resistant clinical isolates, mutant strains overexpressing one of three RND efflux pumps (MexAB-OprM, MexCD-OprJ, and MexEF-OprN), and a strain with the same three pumps deleted were used. MIC assays confirmed that the clinical isolates and the mutants overexpressing efflux pumps were resistant to ciprofloxacin and pentamidine.

Clinical and Genomic Evolution of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections over Two Time Periods at a Tertiary Care Hospital in South India: A Prospective Cohort Study.

Introduction: The objective of this study was to examine the evolution of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections and their impact at a tertiary care hospital in South India.

Methods: A comparative analysis of clinical data from two prospective cohorts of patients with CRKp bacteremia (C1, 2014-2015; C2, 2021-2022) was carried out. Antimicrobial susceptibilities and whole genome sequencing (WGS) data of selected isolates were also analyzed.

Activity of Two Cefepime-Based Novel Combinations, Cefepime/Taniborbactam and Cefepime/Zidebactam, against Carbapenemase-Expressing Collected in India.

In recent times, discovery efforts for novel antibiotics have mostly targeted carbapenemase-producing Gram-negative organisms. Two different combination approaches are pertinent: β-lactam-β-lactamase inhibitor (BL/BLI) or β-lactam-β-lactam enhancer (BL/BLE). Cefepime combined with a BLI, taniborbactam, or with a BLE, zidebactam, has been shown to be promising.

Carbapenem-Only Combination Therapy against Multi-Drug Resistant : Assessment of In Vitro and In Vivo Efficacy and Mode of Action.

The aim of the study was to determine the efficacy of carbapenem-only combination treatments derived from four approved drugs (meropenem, doripenem, ertapenem and imipenem) against a MDR strain of in a larvae infection model. larvae were infected with NCTC 13437 (carrying the VIM 10 carbapenamase) and the efficacy of the six possible dual, four triple, and one quadruple carbapenem combination(s) were compared to their constituent monotherapies. Four of these combinations showed significantly enhanced survival compared to monotherapies and reduced the bacterial burden inside infected larvae but without complete elimination.

A computational investigation of COVID-19 transmission inside hospital wards and associated costs.

The COVID-19 pandemic has placed a particular burden on hospitals: from intra-hospital transmission of the infections to reduced admissions of non-COVID-19 patients. There are also high costs associated with the treatment of hospitalised COVID-19 patients, as well as reductions in revenues due to delayed and cancelled treatments. In this study we investigate computationally the transmission of COVID-19 inside a hospital ward that contains multiple-bed bays (with 4 or 6 beds) and multiple single-bed side rooms (that can accommodate the contacts of COVID-19-positive patients).

Presence of mediated linezolid resistance in multiple lineages and plasmids of revealed by long read sequencing.

Transferable linezolid resistance due to , , and -like genes is increasingly detected in enterococci associated with animals and humans globally. We aimed to characterize the genetic environment of in linezolid-resistant isolates from Scotland. Six linezolid-resistant isolated from urogenital samples were confirmed to carry the gene by PCR.

Probabilistic microsimulation to examine the cost-effectiveness of hospital admission screening strategies for carbapenemase-producing enterobacteriaceae (CPE) in the United Kingdom.

Background: Antimicrobial resistance has been recognised as a global threat with carbapenemase- producing-Enterobacteriaceae (CPE) as a prime example. CPE has similarities to COVID-19 where asymptomatic patients may be colonised representing a source for onward transmission. There are limited treatment options for CPE infection leading to poor outcomes and increased costs.

The association between SARS-CoV-2 RT-PCR cycle threshold and mortality in a community cohort.

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The protective effect of SARS-CoV-2 antibodies in Scottish healthcare workers.

Background: Healthcare workers (HCWs) are believed to be at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is not known to what extent the natural production of antibodies to SARS-CoV-2 is protective against re-infection.

Methods: A prospective observational study of HCWs in Scotland (UK) from May to September 2020 was performed.

Modelling the transmission of infectious diseases inside hospital bays: implications for COVID-19.

Healthcare associated transmission of viral infections is a major problem that has significant economic costs and can lead to loss of life. Infections with the highly contagious SARS-CoV-2 virus have been shown to have a high prevalence in hospitals around the world. The spread of this virus might be impacted by the density of patients inside hospital bays.

Genomic epidemiology reveals multiple introductions of SARS-CoV-2 from mainland Europe into Scotland.

Coronavirus disease 2019 (COVID-19) was first diagnosed in Scotland on 1 March 2020. During the first month of the outbreak, 2,641 cases of COVID-19 led to 1,832 hospital admissions, 207 intensive care admissions and 126 deaths. We aimed to identify the source and number of introductions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into Scotland using a combined phylogenetic and epidemiological approach.

Repurposing the anti-viral drug zidovudine (AZT) in combination with meropenem as an effective treatment for infections with multi-drug resistant, carbapenemase-producing strains of Klebsiella pneumoniae.

Multi-drug resistant (MDR) Klebsiella pneumoniae represent a global threat to healthcare due to lack of effective treatments and high mortality rates. The aim of this research was to explore the potential of administering zidovudine (AZT) in combination with an existing antibiotic to treat resistant K. pneumoniae infections.

Drive-through testing for SARS-CoV-2 in symptomatic health and social care workers and household members: an observational cohort study.

The requirement for health and social care workers to self-isolate when they or their household contacts develop symptoms consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to critical staff shortages in the context of a pandemic. In this report, we describe the implementation of a drive-through testing service in a single National Health Service region in Scotland. From 17 March 2020 to 11 April 2020, 1890 SARS-CoV-2 reverse transcription PCR assay (RT-PCR) tests were performed.

Characteristics and outcomes of health and social care workers testing positive for SARS-CoV-2 in the Tayside region of Scotland.

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Rapid molecular testing for bacteraemia improves clinical management.

bacteraemia (SAB) causes significant morbidity and mortality. Standard diagnostic methods require 24-48 h to provide results, during which time management is guideline-based and may be suboptimal. Evaluate the impact of rapid molecular detection of in positive blood culture bottle fluid on patient management.