bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmodium falciparum Malaria Is Associated With Increased Kaposi Sarcoma–Associated Herpesvirus (KSHV) Seropositivity and Higher KSHV Antibody Breadth and Magnitude: Results of a Case-Control Study From Rural Uganda
Authors: Nalwoga Angela , Sabourin Katherine R , Miley Wendell , Jackson Conner , Maktabi Mahdi , Labo Nazzarena , Mugisha Joseph , Whitby Denise , Rochford Rosemary , Newton Robert 
Published: August 2023

Abstract

Background
Previously, we showed that children with asymptomatic Plasmodium falciparum (Pf) malaria infection had higher Kaposi sarcoma–associated herpesvirus (KSHV) viral load, increased risk of KSHV seropositivity, and higher KSHV antibody levels. We hypothesize that clinical malaria has an even larger association with KSHV seropositivity. In the current study, we investigated the association between clinical malaria and KSHV seropositivity and antibody levels.

Methods
Between December 2020 and March 2022, sick children (aged 5–10 years) presenting at a clinic in Uganda were enrolled in a case-control study. Pf was detected using malaria rapid diagnostic tests (RDTs) and subsequently with quantitative real-time polymerase chain reaction (qPCR). Children with malaria were categorized into 2 groups: RDT+/PfPCR+ and RDT–/PfPCR+.

Results
The seropositivity of KSHV was 60% (47/78) among Pf-uninfected children, 79% (61/77) among children who were RDT–/PfPCR+ (odds ratio [OR], 2.41 [95% confidence interval {CI}, 1.15–5.02]), and 95% (141/149) in children who were RDT+/PfPCR+ (OR, 10.52 [95% CI, 4.17–26.58]; Ptrend &lt; .001). Furthermore, RDT+/PfPCR+ children followed by RDT–/PfPCR+ children had higher KSHV IgG and IgM antibody levels and reacted to more KSHV antigens compared to uninfected children.

Conclusions
Clinical malaria is associated with both increased KSHV seropositivity and antibody magnitude, suggesting that Pf is affecting KSHV immunity.
O02 Nitrofurantoin: what is the evidence for current guidance?
Authors: Kashouris Eleanor , Joseph Amelia , Lewis Tom 
Published: August 2023

Abstract
In this abstract, we review current approaches to the management of uncomplicated urinary tract infection (UTI) and begin to explore alternative approaches to antibiotic prescribing. We review clinical guidelines on the use of nitrofurantoin internationally to capture the level of variation in evidence-based guidance. We find that the evidence base has been interpreted in very different ways. UK guidelines from NICE and the Scottish Intercollegiate Guidelines Network (SIGN) are unusual in promoting short (3 day) courses of nitrofurantoin. We find little direct evidence to support this, and that this guidance has been extrapolated from studies based on other agents. ‘Short’ courses of antibiotics aim to provide optimum balance between providing effective treatment whilst reducing selective pressure driving resistance amongst colonizing microbial flora. Three days of nitrofurantoin may indeed be a useful intervention in a large group of patients. Longer courses of nitrofurantoin still demonstrate considerable rates of treatment failure. The concept of a course length in itself is limited. The variation between recommendations internationally reflects both the uncertain foundations upon which evidence-based guidelines are written, and the limits of what can be safely concluded from evidence. We join others in pointing out there may be ways of customizing duration of therapy to the patient’s response in primary care settings. There is a need for a more patient-focused approach to uncomplicated UTI, including better safety-netting and (currently lacking) guidance on best practice in the common clinical scenario of treatment failure.
O03 The effect of antibiotic selection on collateral susceptibility and evolvability of uropathogenic Escherichia coli
Authors: Hubbard Alasdair T M , James Beth , Whelan Rachel , Meehan Conor , Domingo Sananes Maria Rosa 
Published: August 2023

Abstract
Urinary tract infections (UTIs) are a common infection in healthy adult women and as such account for 1%–3% of all medical consultations and the second most common reason for prescribing antimicrobials in the UK. Escherichia coli is a frequent aetiological agent of uncomplicated UTIs, causing 75% of cases, associated with recurrence of infection (40%) and a major source of bacteraemia (∼40%). Trimethoprim and nitrofurantoin are currently recommended as first-line antibiotics for the treatment of uncomplicated UTIs. However, 48700 deaths in Europe in 2019 have been associated with antimicrobial-resistant UTIs and resistance to trimethoprim in community-acquired UTIs caused by E. coli is high (33.4%). With little to no antimicrobial development in recent years, new strategies are therefore required to maintain efficacy in currently available antibiotics. One such strategy is to use evolutionary principles to understand how antimicrobial resistance (AMR) to one antibiotic can affect the activity and probability of resistance development to a second antibiotic. Effect on antimicrobial activity can be assessed through collateral susceptibility, where prior resistance to one antibiotic either increases or decreases susceptibility to a second, unrelated class of antibiotic. While the probability of resistance development can be assessed by the mutant selection window (MSW), an antibiotic concentration range where AMR mutations can be selected for. This ranges from the MIC (the lowest concentration to select for resistance) to the mutant prevention concentration (MPC, the highest concentration to select for resistance). In this study, we aimed to determine the effect trimethoprim resistant derivatives of three clinical strains of uropathogenic E. coli on collateral susceptibility and MSWs to nitrofurantoin. We found that trimethoprim-resistant mutants conferred the expected decrease in susceptibility to trimethoprim and an increase in the MSW. This suggests prior selection with trimethoprim increases the probability of treatment failure and the selection of further mutations conferring high-level resistance to trimethoprim. We also observed collateral resistance to nitrofurantoin in the trimethoprim-resistant mutants. Importantly, however, there was a reduction in the MPC, and therefore a narrowing of the MSW, reducing the probability of selection of higher levels of nitrofurantoin resistance. This suggests that using nitrofurantoin after trimethoprim may reduce the probability of developing nitrofurantoin resistance compared with using nitrofurantoin first. These data provide a potential evidence base to use evolutionary principles when designing antimicrobial regimens to limit AMR development and improve treatment success.
P14 Optimization of real-time sequencing for rapid detection of bacterial species and antimicrobial resistance in blood and urine infections
Authors: Getino Maria , Stout Rebecca , Davies Frances , Jauneikaite Elita 
Published: August 2023

Abstract

Objectives
To optimize the process to obtain bacterial DNA directly from human urine and blood samples to produce high-quality genomic data using long-read Nanopore sequencer.

Methods
A total of 22 blood cultures and 24 urine samples positive for Escherichia coli or Klebsiella pneumoniae and corresponding isolates were collected from the microbiology diagnostics laboratory. DNA isolation optimization was performed testing three different sample volumes and seven DNA extraction kits. DNA concentration was quantified with Qubit fluorometer. Nanopore sequencing was performed on a MinION Mk1C device in R9.4.1 flow cells using the Rapid Barcoding Kit. Bacterial species and antimicrobial resistance (AMR) genes were determined with EPI2ME ARMA pipeline. Genomes were assembled with Flye, polished with Medaka and remaining human contigs removed with Krakentools. Bacterial isolates from the same samples were also sequenced using Illumina technology. Illumina and Nanopore assemblies were quality checked with Quast, Kraken was used to identify bacterial species, MLST for multilocus sequence typing and ABRicate with ResFinder database to detect AMR genes.

Results
A total of 72 DNA extractions from 24 urine and 22 blood samples with different kits were performed to find the optimal extraction protocol for each sample type. DNA from urine samples was isolated from 5 mL, while 1 mL was best for blood cultures. We found that the host depletion step prior to DNA extraction using MolYsis basic 5 Kit (VH-Bio) was essential. DNA from urine samples was extracted with GenElute Bacterial Genomic DNA Kit (Merck) and QIAamp Biostic bacteremia Kit (Qiagen) was best to allow successful bacterial genome sequencing for blood samples. Bacterial isolates from 11 urine and 1 blood sample (out of 54 sequenced) were successfully sequenced. In all 12 cases, the highest percentage of bacterial reads matched with the causative organism found during routine microbiology diagnostics (E. coli). A variety of clinically relevant AMR genes were detected, such as dfrA and bla CTX-M genes, which matched the phenotypic antimicrobial susceptibility testing results. Comparison of genomic assemblies obtained through Nanopore sequencing of 10 urine samples and Illumina sequencing of the corresponding clinical isolates showed a high degree of matching, validating Nanopore sequencing as an alternative option to support diagnosis and treatment choice.

Conclusions
We have successfully optimized the protocols to extract and sequence pathogenic bacterial DNA directly from blood and urine samples. Short-read sequencing confirmed results acquired by Nanopore sequencer, endorsing long-read sequencing in clinical settings to support timely diagnosis and treatment.
P19 Burden of illness and costs among female patients with uncomplicated urinary tract infection in England
Authors: Wilcox Mark , Heaton Dave , Mulgirigama Aruni , Joshi Ashish V , Chirikov Viktor , Gibbons Daniel C , Webb David , Marston Xiaocong , Alexander Myriam , Mitrani-Gold Fanny S 
Published: August 2023

Abstract

Background and Objectives
Uncomplicated urinary tract infection (uUTI) is usually community-acquired. Data regarding the wider burden of illness from uUTI are scarce. We evaluated the burden of uUTI in female patients in England.

Methods
This retrospective comparative cohort study utilized linked anonymized patient data from 1 January 2017 to 29 February 2020 from the Clinical Practice Research Datalink (CPRD) and English Hospital Episode Statistics databases. All eligible patients were female, aged ≥12 years and had ≥12 months’ CPRD data available pre- and post-index (i.e. ≥24 months total). Patients with an index UTI diagnosis who had received ≥1 oral antibiotic within ±5 days of index formed the uUTI cohort; uUTI episodes were defined as 28 days from index diagnosis. Patients who had visited a primary care setting but did not have a UTI (uUTI or complicated UTI [cUTI]) diagnosis during the study period formed the control cohort and were matched to the index date of uUTI patients. Patients who were hospitalized or visited an accident and emergency department 28 days prior to index, had cUTI and/or had received IV antibiotics as initial therapy were excluded. Burden of illness (index/12 month follow-up all-cause and UTI-related healthcare resource use [HCRU] and costs) was evaluated in a 1:1 age- and Charlson Comorbidity Index (CCI) score-matched cohort.

Results
Overall, 120519 female patients with uUTI and 233670 female control patients (without uUTI) were identified and matched 1:1. Before matching, more of the uUTI cohort patients versus controls were &lt;50 years old, had a higher mean CCI score, and were more often menopausal; region- and practice-level differences were modest (Table 1). HCRU and costs were significantly higher among uUTI patients versus matched controls, notably for primary care, specialist, and accident and emergency visits, and hospital admissions (P&lt;0.001, Table 2). After adjusting for patient characteristics, Poisson or negative binomial models showed significant HCRU differences in primary and secondary care for uUTI patients versus matched controls (Table 3).

Conclusions
Patients with uUTI in England had significantly higher burden of illness, consuming more resources, during index uUTI episodes and follow-up, versus matched controls.
P23 Prevalence of asymptomatic bacteriuria and associated risk factors in an adult population relevant to UK primary care: a systematic review and meta-analysis
Authors: Moore Abi , Coyle Conor , Seeley Anna , Cherrington-Walker Phoebe , Khan Maaedah , Fanshawe Thomas , Pouwels Koen , Lecky Donna , Hayward Gail , Cooper Emily 
Published: August 2023

Abstract

Background
The use of urine dipstick tests in people who are more likely to have asymptomatic bacteriuria (ASB) can lead to the over-diagnosis of urinary tract infection (UTI) and unnecessary antibiotic prescribing. As a result, urine dipsticks are not recommended in those over the age of 65 years, or those with a urinary catheter in UK primary care guidelines. However, due to variation in prevalence estimates for ASB and the age of some of the existing prevalence studies it is unclear whether the use of age 65 as a cut-off for dipstick testing remains appropriate.

Objectives
This systematic review aims to identify and synthesize more recent evidence around ASB prevalence and other risk factors relevant to a UK community context, in order to improve how UK primary care UTI diagnostic guidance addresses asymptomatic bacteriuria.

Methods
The protocol for this systematic review is registered with PROSPERO. Inclusion criteria are: study participants aged ≥18 years; prospective studies recruiting from a primary care relevant population; studies that measure ASB prevalence and risk factors; and studies from the Organization for Economic Co-operation and Development member countries. Exclusion criteria include: studies from inpatient hospital settings (including the emergency department); studies exclusively including people who are pregnant, who have urinary catheters, who are post renal transplant or who have structural urological abnormalities; animal studies; laboratory studies; studies published before 1990; and studies not written in English. Searches were conducted in CINAHL, Embase and Medline using MeSH and free text words adapted for each database including terms for bacteriuria AND asymptomatic disease. The Cochrane Collaboration Covidence platform is being used for the management of screening and assessment of studies. Two authors are independently completing screening, data extraction and quality assessments.

Results
The initial search identified 3891 studies. After screening, 685 are currently undergoing full text review. Overall findings will be reported in a narrative synthesis. We will describe the studies identified, including how ASB has been defined within each of the studies. If sufficient data are available we will complete a meta-analysis. Using standard meta-analysis methods we will generate forest plots showing prevalence and 95% CIs for each study. If possible, we will estimate pooled prevalence of ASB from the reported prevalence of eligible studies, by age group and gender.

Conclusions
The results of this review may highlight where new evidence around ASB prevalence and risk factors relevant to a UK primary care population is needed.
P26 Evaluating the antibacterial activity of recombinant phage-encoded lysin against drug-resistant uropathogenic Escherichia coli
Authors: Dhar Sakshi , Nain Sonia , Gupta Vaishali , Gaharwar Utkarsh , Chavan Bhakti , Das Ritam , Hanif Sarmad , Bajpai Urmi , Sikriwal Deepa , Choudhary Aasiya , Syeda Safia , Shah Sanket , Ahmed Syed 
Published: August 2023

Abstract

Background
Atrocious use of antibiotics has led to the emergence of MDR in uropathogenic Escherichia coli (UPEC) that poses a serious challenge in the management of urinary tract infections (UTIs). The WHO has described antibiotic resistance in uropathogens as a key pressure point in the burgeoning global antimicrobial resistance crisis. Given this grim situation, we are exploring phage-encoded lysins as plausible alternatives.

Objectives
Our study involved an in silico strategy for the discovery and characterization of lysin sequences (seq) targeting E. coli cell wall and evaluating the bactericidal activity of these recombinant lysins using in-vitro assays.

Methods
Novel lysin sequences were searched by BLAST homology and by screening E. coli prophages in the database (using PHASTER). Lysozyme-like domain was observed in 9 out of 16 lysins. Their characterization depicted modular or globular structure. Based on the physicochemical properties, 7 out of 16 lysins were selected for cloning, expression, and purification as recombinant proteins for evaluating the bactericidal activity.

Results
Among the several lysins screened, lysin seq 5 demonstrated the highest activity using in vitro assays. Using static biofilm assay, lysin seq 5 (180 μg) showed efficient reduction (&gt;50%) in the biofilm formed by ATCC UPEC 700928 strain. As per turbidity reduction method, lysin seq 5 (50 μg) showed 37% drop in OD600nm on UPEC 700928 strain after 3 h of incubation at 37°C. Using spot on lawn assay, lysin seq 5 (20 μg) exhibited lytic activity (zone of inhibition) on five drug-resistant clinical UTI isolates, which were pretreated with an outer membrane permeabilizer (OMP), viz., EDTA (0.3 mM).

Conclusions
Lysin seq 5 exhibited antibiofilm activity against UPEC 700928 strain as well as lytic activity against drug-resistant clinical UTI isolates. Screening of additional drug-resistant clinical isolates from UTI patients is underway.
P27 Rethinking UTI diagnosis: how gold is the ‘gold standard’ and how much does antimicrobial susceptibility testing really matter?
Authors: Diggle Joanna , Nieuwland Jeroen , Hayhurst Emma 
Published: August 2023

Abstract

Objectives
To analyse the results provided by culture methods for UTI diagnosis and estimate its potential effectiveness for clinical decision making.

Methods
The results of all 80981 urine samples processed by the Public Health Wales laboratory in Cardiff in 2022 were collated and analysed. Prevalence and resistance data were collected and analysed using Datastore. Specific aims were as follows: (i) determine the prevalence of ‘no growth’ and ‘mixed growth’ samples, and of each individual uropathogen; (ii) determine resistance rates for each pathogen; and (iii) estimate the potential effectiveness of these culture results for making clinical decisions.

Results
Of the 80981 urine samples analysed, 22775 (28%) were negative following flow cytometry analysis and were not cultured. Of the 58206 urine samples cultured, 18656 (32%) showed no growth and 20516 (35%) showed mixed growth and were not analysed further. A total of 19034 (33%) showed growth of one or more specific pathogens. The most common uropathogen was Escherichia coli (58%), followed by Klebsiella pneumoniae (8.6%), Enterococcus spp. (7.3%) and Proteus mirabilis (4.2%). Resistance rates varied by pathogen. Resistance to nitrofurantoin in E. coli was low (2.4%) but resistance to trimethoprim amongst E. coli isolates was higher (30.5%). Klebsiella, Pseudomonas and Proteus spp. were not routinely tested for resistance to nitrofurantoin, presumably due to high levels of inherent resistance. Of the 22 P. mirabilis isolates tested, all were resistant to nitrofurantoin. Trimethoprim resistance was high for all species routinely tested. Only 24% of all samples analysed returned an antimicrobial susceptibility test (AST) result. AST results relevant to the first-choice antibiotics of nitrofurantoin or trimethoprim were obtained for only 16% and 19% of all urines tested, respectively. Overall resistance to nitrofurantoin was 2.8% and to trimethoprim 32%, representing 0.44% and 6% of total samples tested, respectively.

Conclusions
These results highlight issues with laboratory culturing. Over one-third of all samples cultured did not return a usable clinical result due to mixed growth and AST results were returned for less than one-quarter of all samples tested. The clinical utility of AST depends on the specific antibiotic and species being tested. With nitrofurantoin resistance currently so low in all species routinely tested, knowing whether there is an infection and which bacteria is causing it will have more impact than performing susceptibility testing for this antibiotic. However, for trimethoprim, resistance rates are higher and more variable, so AST has more potential clinical impact.
P29 Catheter-associated urinary tract infections, potential for diagnostic and antimicrobial stewardship
Authors: Kelly Siobháin , O’ Donnell Sinead , Powderly Ailish , Fitzpatrick Fidelma 
Published: August 2023

Abstract

Background and Objectives
Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections.1 Microbiological investigation of catheter specimens of urine (CSUs) results in a significant workload for microbiology laboratories. As bacteria cultured from CSUs often reflect colonization rather than infection, we must prudently interpret these culture results and judiciously prescribe antimicrobials in this setting. For these reasons, we felt it was important to assess if CAUTIs are being appropriately investigated and managed in our hospital.

Methods
We identified all the CSUs received in the microbiology laboratory from inpatients over a 7 day period in an 820-bed adult tertiary referral hospital. Once identified, a retrospective review of each patient’s clinical and drug charts was undertaken. The CDC definition of CAUTI was applied for the purpose of this audit.2

Results
A total of 126 CSUs from 101 patients were included. The majority of patients (n=79, 78%) had a urinary catheter introduced during their hospital admission. At the time of CSU sampling, suspicion of infection was documented in only 47 patients. Only 9% of patients who had a CSU processed met the criteria for a CAUTI.2 Fifty-six percent of patients were commenced on antibiotics, despite only 31% returning a culture positive CSU sample. CSU results were documented in only 10% of patient charts. In cases where a CAUTI was suspected, it took an average of 6.75 days for the urinary catheter to be exchanged or removed. Four patients continued to receive an antibiotic despite the organism isolated being reported as resistant.

Conclusions
Overall, we noted that there was poor documentation of both urinary catheter status and of CSU results. Our audit revealed that several patients had multiple specimens processed within the 7 day period. Most patients had no clear indication for CSU sampling. From an antimicrobial stewardship perspective, there was unnecessary and inappropriate prescribing of antimicrobials. The results of this audit show that there is potential for both diagnostic and antimicrobial stewardship in the management of CAUTIs.
Radio emission from the first quasars at z = 6–15
Authors: Latif Muhammad A , Whalen Daniel J , Mezcua Mar 
Published: August 2023

ABSTRACT
Nearly 300 quasars have now been found at z &gt; 6, including nine at z &gt; 7. They are thought to form from the collapse of supermassive primordial stars to 104–105 M⊙ black holes at z ∼ 20–25, which then rapidly grow in the low-shear environments of rare, massive haloes fed by strong accretion flows. Sensitive new radio telescopes such as the Next-Generation Very Large Array (ngVLA) and the Square Kilometre Array (SKA) could probe the evolution of these objects at much earlier times. Here, we estimate radio flux from the first quasars at z ∼ 6–15 at 0.5–12.5 GHz. We find that SKA and ngVLA could detect a quasar like ULAS J1120+0641, a 1.35 × 109 M⊙ black hole at z = 7.1, at much earlier stages of evolution, z ∼ 14–16, with 100 h integration times in targeted searches. The advent of these new observatories, together with the JWST, Euclid, and the Roman Space Telescope, will inaugurate the era of z ≲ 15 quasar astronomy in the coming decade.