bluuebunny/crossref_metadata_2025 huggingface dataset:
Tomato-Associated Archaea Show a Cultivar-Specific Rhizosphere Effect but an Unspecific Transmission by Seeds
Authors: Taffner Julian , Bergna Alessandro , Cernava Tomislav , Berg Gabriele
Published: March 2020

Archaea have recently been identified as substantial members of the plant microbiome. As for other microorganisms, the rhizosphere is a favorable habitat for archaea; however, less is known about their community assembly, composition, or origin. Therefore, we analyzed archaeal communities in the rhizosphere of tomato plants (Solanum lycopersicum ‘Moneymaker’ and ‘Hildares F1’) nurtured in two different soil types. In complementary experiments, archaeal communities were assessed in two generations of tomato seeds. The abundance of the archaea was significantly different for each plant genotype and habitat. In the rhizosphere of Moneymaker, the archaeal abundance was 10-fold higher than in Hildares F1, whereas the decrease in archaeal abundance from seeds of the first generation to the second was much higher by 104-fold in the same cultivar. Overall, the archaeal community in tomato was dominated by Thaumarchaeota and Euryarchaeota. The core community in tomato consisted of species assigned to the Soil Crenarchaeotic Group (Thaumarchaeota; 60.7%), Methanosarcina (Euryarchaeota; 12.6%), Methanoculleus (Euryarchaeota; 3.4%), and unassigned archaeal species (7.2%). Differences in abundance, diversity, and composition between cultivars were so distinct that they masked any effect determined by the different composition of soil. In seeds, archaeal abundance and diversity was comparably low and the composition showed random patterns; no indications of a plant-mediated vertical transmission were found. We assume that archaea represent only bystander microorganisms in seeds, while their cultivar-specific enrichment in the rhizosphere suggests a role in functioning of the plant holobiont.
Switchgrass Rhizosphere Metabolite Chemistry Driven by Nitrogen Availability
Authors: Smercina Darian N. , Bowsher Alan W. , Evans Sarah E. , Friesen Maren L. , Eder Elizabeth K. , Hoyt David W. , Tiemann Lisa K.
Published: March 2020

Plants and soil microorganisms interact closely in the rhizosphere where plants may exchange carbon (C) for functional benefits from the microbial community. For example, the bioenergy crop, switchgrass (Panicum virgatum) is thought to exchange root-exuded C for nitrogen (N) fixed by diazotrophs (free-living N-fixers). However, this interaction is not well characterized and it is not known how or if switchgrass responds to diazotrophs or their activity. To explore this question, we assessed rhizosphere metabolite chemistry of switchgrass grown in a hydroponic system under two N levels and under inoculated or uninoculated conditions. Plants were grown with the inoculum Azotobacter vinelandii DJ for 3 days before harvest. We found switchgrass root exudate chemistry to be driven by N availability. Total metabolite concentrations were generally greater under high N versus low N and unaffected by inoculation. Examination of rhizosphere chemical fingerprints indicates metabolite chemistry was also driven strongly by N availability with a greater relative abundance of carbohydrates under high N and greater relative abundance of organic acids under low N. We also found evidence of changes in rhizosphere chemical fingerprints by inoculation treatment. However, we found little evidence of N treatment and inoculation interaction effects that suggests this response is not directly mediated by N availability.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Phenotypic variation of Gardnerella vaginalis subgroups in relation to virulence potential
Authors: Bulavaitė Aistė , Janulaitienė Miglė , Baranauskienė Lina , Gėgžna Vilmantas , Plečkaitytė Milda
Published: March 2020

Background

Phenotypic and genotypic diversity of vaginal bacteria Gardnerella vaginalis resulted in its classification into genotypic subgroups. The virulence potential of these subgroups was evaluated.

Methods

G. vaginalis clinical isolates were subtyped on the basis of subgroup-specific genes by PCR. The virulence-related phenotypic characteristics of the isolates were evaluated assessing their in vitro ability to grow as biofilm on abiotic surfaces, produce the toxin vaginolysin, and express sialidase activity. Vaginolysin in the supernatant of the cultures was quantified using toxin-specific antibodies by sandwich ELISA. Sialidase activity was tested using fluorogenic substrate. Cloning and expression of the sialidase gene of G. vaginalis in E. coli was performed. Differences in the expression of phenotypic properties of the isolates were evaluated by agglomerative hierarchical clustering and principal component analysis.

Results

Thirty-five clinical isolates of G. vaginalis were subtyped into three subgroups 1, 2 and 4. Analysis of sialidase activity indicated statistically significant differences among the subgroups. All isolates were grouped into three clusters by the methods of statistical analysis. The distinct profile of each cluster was based on the phenotypic characteristics of isolates. Subgroup 4 was the most homogenous group, as all isolates were found in the same cluster, which was characterized by the low production of all studied virulence factors. Subgroup 2 isolates were mainly distributed between two clusters, whereas subgroup 1 isolates were found in all three clusters.

Conclusion

G. vaginalis subgroups with different virulence potential might play distinct roles in vaginal microbiota.
Is hand surface coverage a good measure of hand hygiene effectiveness?
Authors: Gozdzielewska Lucyna , Price Lesley , McAloney Kareena , Lang Sue , Reilly Jacqui
Published: March 2020

Background: Effective hand hygiene (HH) is fundamental to the prevention of healthcare-associated infections. One of the commonly used ways for assessing the effectiveness of HH procedure is measuring the extent of hand surface coverage with alcohol-based handrub (ABHR).

Methods: In this Latin square design study, handrubbing with ABHR was performed seven times by each of the 35 volunteers. Volunteers’ hands were contaminated with the Escherichia coli K12 strain as per EN 1500 guidelines. Glove juice samples were collected from their hands before and after each ABHR application and surface coverage was measured using Hand-in-Scan® scanner. The relationship between the bacterial log10 reduction and percent surface coverage was analysed using Spearman’s Rank Order Correlation and simple linear regression.

Results: Surface coverage ranged from 49.38% to 100% (N= 208, Mdn: 97,33%, IQR= 83.52 – 99.93), while the E. coli reduction ranged from 0.96 to 5.92 log10 (N= 221, M: 3.07, SD= 0.94). The Spearman’s Rank Order Correlation results showed no significant correlation between percent hand surface coverage and E. coli log10 reduction [r= -0.009, n= 198, p= 0.905]. The lack of correlation was further confirmed by the linear regression.

Conclusions: These findings suggest that the rate of surface coverage does not correlate with reduction in bacterial load on hands following HH. Although visual feedback on surface coverage can be a good approach to teaching the correct HH technique, these findings suggest that surface coverage alone is not a reliable measure of HH effectiveness.
Doxycycline for the empiric treatment of low-severity hospital acquired pneumonia
Authors: Cevik Muge , Russell Clark , Evans Morgan , Mackintosh Claire
Published: March 2020

Background

In the U.K., doxycycline is widely recommended as first-line empiric treatment for mild HAP, however this practice is based on expert opinion and we are aware of no data describing the outcomes of patients treated with doxycycline. Here we describe the outcomes of non-ICU patients treated empirically with doxycycline for low-severity HAP.

Methods

1680 inpatient chest x-rays were manually screened to identify cases of HAP. HAP was defined as new or progressive CXR consolidation occurring ³48 hours after admission, combined with compatible symptoms or signs. Treatment failure was defined as requirement for antimicrobial escalation, HAP recurrence or mortality attributed to HAP. We compared groups according to treatment outcome using the Kruskal-Wallis test and receiver operator characteristic (ROC) analysis.

Results

Forty-nine patients who received doxycycline were included in the analysis. The median age was 78 years and 63% had >2 co-morbidities. Hypoxia was common (57%) but extra-pulmonary organ dysfunction was uncommon. 71% of patients were successfully treated with doxycycline as first-line empiric therapy. Treatment failure was associated with increased duration of hospitalisation prior to HAP onset (median 21.5 vs. 10 days, p=0.03) and higher neutrophil count (10.1 vs. 6.1 x109L-1, p=0.04). ROC analysis identified HAP onset >14 days after admission as the optimum cut-off for predicting treatment failure.

Conclusions

In this cohort, the majority of patients with low-severity HAP were successfully treated with doxycycline. Treatment failure was associated with prolonged hospitalisation prior to HAP onset with 14d identified as a potential surrogate marker for patients requiring antimicrobials against Gram-negative organisms.
Post-influenza meningitis in an immunosuppressed man
Authors: Senanayake Rashantha , Burns Daniel , Canning Benjamin , Dedicoat Martin , Moran Ed
Published: March 2020

Background:

We report a case of post-influenza invasive aspergillosis causing ventriculitis in a patient immunosuppressed on methotrexate for rheumatoid arthritis.

A 63-year-old male with a positive H1N1 throat swab presented with increasing dyspnoea and pyrexia that failed to improve despite broad-spectrum antibiotics and zanamivir. Imaging of his chest showed cavitating lung disease and a possible post influenza fungal infection. He was initiated on antifungal treatment that was stopped after 10 days following a negative bronchoalveolar lavage and serum galactomann test. Respiratory symptoms and inflammatory markers improved but he developed confusion and falls. Computed tomography of the head showed hydrocephalus but there was no papilloedema. Examination of the cerebrospinal fluid (CSF) showed lymphocytosis with elevated proteins but negative initial investigations. Subsequent magnetic resonance imaging of the head with contrast showed obstructing hydrocephalus with ventriculitis. He underwent an urgent ventriculostomy by the neurosurgeons which demonstrated purulent CSF. CSF testing was strongly positive for beta-D glucan, a positive PCR result for aspergillus in CSF was received from the initial lumbar puncture and histology from operative samples showed fungal hyphae. Dual antifungal treatment was recommenced but the patient’s conditioned worsened, and he died on ITU.

Conclusion:

Whilst invasive pulmonary aspergillosis is a recognised complication of influenza, extrapulmonary infection is less well documented. This is the first case in the literature in which ventriculitis due to aspergillus is described as a sequel to infection with influenza. Clinicians should remain vigilant for fungal infection in patients with influenza who are immunosuppressed.
Developing a quality assurance system for the use of stimulan beads in a diabetic foot clinic
Authors: Burns Phillipa , Adams Kate , Hajjawi Mark , Wearmouth Deborah
Published: March 2020

Background

Diabetic foot infections are an increasing healthcare issue and managing these infections can be difficult. A recent innovation in the way they are managed in the Hull clinic is the use of antibiotic impregnated (generally Gentamicin and Vancomycin) STIMULAN beads. Often only a couple of beads can be used in a foot wound making it a very uneconomical strategy if the beads can’t be stored and used on other wounds. There is no recommended quality assurance method provided by the manufacturers to validate this practice leading to this study.

Methods

Five beads were removed from a batch; at 1, 4, 8 and 12 week intervals for testing:

Bacterial Challenge: a 10mL spot of bead suspension was placed on Mueller Hinton seeded with Staphylococcus aureus ATCC 29213 and E. coli ATCC 25922 and incubated in Air, at 35±1ºC for 18±2hrs; zones of inhibition were read and recorded.

TDM: Vancomycin and Gentamicin levels present in each bead was established by analysing 50mL of suspension (1:5 DF) using a therapeutic drug monitoring assay.

Results

Beads were microbiologically active for 12 weeks with no notable loss of potency.

Bacterial challenge: Staphylococcus aureus range 17-23mm, av. 20.4mm and E. coli range 11-20mm, av. 17.5mm.

TDM Assay: Vancomycin range 62.01 – 110.18 Av. 88.88mg/L, Gentamicin range 20.38 – 27.41 Av.23.20mg/L.

Conclusion

Quality assurance of the STIMULAN beads can be established using standard TDM assays and microbiological activity, enabling a kit to be used for up to 12 weeks with clinical confidence.
Is prior antibiotic exposure a risk factor for the development of bacteraemia in bone marrow transplant patients?
Authors: Hills George , Dulobdas Vaishali , Perera Nelun
Published: March 2020

Background: Bone marrow transplantation (BMT) is a unique immunosuppressed state, and the consequences of infection are often severe. We hypothesized that disruption of the faecal microbiota (such as with use of broad spectrum antibiotics) may predispose to gastrointestinal related sepsis post bone marrow transplantation.

Methods: We reviewed the laboratory data from all BMT patients between January 2016 and August 2018 and recorded the presence of bacteraemia. We matched these patients to controls with no recorded bacteraemia. We then recorded antibiotic exposure in the immediate pre-transplant period.

Results: 238 records were reviewed (81 allografts, 157 autografts). We identified 28 patients with bacteraemia from gastrointestinal related pathogens. 28 controls with no positive blood cultures were matched according to the type of BMT. In both groups there were 18 allografts, 12 of which were matched unrelated donors. In the bacteraemic group there were a total of 12 antibiotic episodes (60 days) pre-transplant, compared with 6 (41 days) in the control group. The most common antibiotics used were meropenem (47 days in the bacteraemic group, 24 control) and piperacillin/tazobactan (13 days in the bacteraemic group, 3 control).

Conclusion: Our results support the hypothesis that broad spectrum antibiotics pre-transplant may predispose to post-transplant sepsis. Although the small population size limits this study, further studies are necessary to confirm this finding, and to investigate which components of the faecal microbiota are the most important to preserve prior to BMT. This may open the door to novel therapeutics in this patient group, such as faecal microbiota transplant.
Pharmacokinetics of TKM-130803 in Ebola virus disease in Sierra Leonean subjects
Authors: Scott Janet , Sharma Raman , Meredith Luke , Dunning Jake , Moore Catrin , Sahr Foday , Ward Steve , Goodfellow Ian , Horby Peter , team RAPIDE-TKM trial
Published: March 2020

TKM-130803 is a specific anti-EBOV therapeutic comprising of two small interfering RNAs (siRNA) siLpol-2 and siVP35-2. The pharmacokinetics (PK) of these siRNAs was defined in Ebola virus disease (EVD) patients. The relationship between PK and patient survival was explored.

Plasma concentration of siRNA was compared to survival at 14 days for seven subjects with EVD in Sierra Leone who received 0.3 mg/kg of TKM-130803 by intravenous infusion over 2 hours daily for up to 7 days. PKdatawere fitted to two-compartment models then Monte Carlo simulated PK profiles were compared to ET (Cmax 0.04-0.57 ng/mL and mean concentration 1.43 ng/mL), and TT (3000 ng/mL).

siRNA was in quantitative excess of virus genomes throughout treatment, but the 95% percentile exceeded TT. Plasma concentration of both siRNAs were higher in subjects who died compared to subjects who survived (p<0.025 both siRNAs).The maximum AUC for which the 95% percentile remained under TT was a continuous infusion of 0.15mg/kg/day.

TKM-130803 was circulating at sufficient concentrations, considered needed for efficacy but given extremely high viral loads it seems likely that the patients died because they were physiologically beyond the point of no return. Subjects who died exhibited some indication of impaired drug clearance, justifying caution in dosing strategies for such patients. This analysis has given a useful insight into the pharmacokinetics of the siRNA in the disease state andillustrates the valueof designing PKPD studies into future clinical trials in epidemic situations.
Case-control study of recurrent Extended-Spectrum Beta Lactamase Enterobacteriaceae Urinary Tract Infections (ESBL UTIs): the management challenges
Authors: Ghani Rohma , Mullish Benjamin , Thursz Mark , Marchesi Julian , Ghazy Anan , Davies Frances
Published: March 2020

Recurrent UTIs are associated with increased hospitalisation and antibiotic use. We investigated patients with recurrent ESBL versus non-ESBL UTIs to identify risk factors and potential treatments.

A30 month retrospective case-control study was performed in patients with recurrent EBSL versus non-ESBL UTI. Definition :1) > three in a year (>two weeks apart) or 2) > two in six months (>one week apart) with the same profile. 3) ESBL UTIs were Enterobacteriaceae resistant to cefalexin AND ceftazadime/ceftriaxone.

281/1449 “recurrent UTI” patients were ESBLs. Patients were more likely to be older, male, with associated bacteraemia, colonisation with carbapenemase-producing Enterobacteriaceae (CPE) and higher resistance rates to non beta-lactam antibiotics. 75% of renal patients were transplant cases, 81% of urology patients had a tube insertion.

Recurrent ESBL UTIRecurrent non-ESBL UTIp value

Number (%)Number (%)(Chi-squared test)

Patients 281 1168

Organism Klebsiella spp (%)42 (14.9) 10 (0.8) <0.001

E coli (%)199 (70.8)811 (69.4)0.665

Demographics Age (mean, SD)64.1, 19 58.7, 22 <0.001

Male 137 (48.8)328 (28) <0.001

Associations Gram negative bacteraemia 35 (12.4) 37 (3.1) 0.001

Colonisation with CPE 21 (7.5) 31 (2.7) <0.001

Speciality Renal 84 (30.0) 196 (16.8)<0.001

Urology 47 (16.7) 104 (8.9) <0.001

Resistance Trimethoprim 219 (77.9)354 (30.3)<0.001

Ciprofloxacin 214 (76.2)160 (13.7)<0.001

Gentamicin135 (48). 64 (5.5) <0.001

ESBL infection is associated with worse outcomes and significant premorbid conditions. The oral crossover resistance prevented long term prophylaxis.

Options are needed to reduce colonisation burden of resistant organisms such as faecal microbiota transplantation.
Nanoplexes molecular patterns for vancomycin efficacy against methicillin-resistance Staphylococcus aureus
Authors: Hassan Daniel , Omolo Calvin A. , Mocktar Chunderika , Govender Thirumala
Published: March 2020

The difficulty in treating life-threatening infections caused by MRSA is a global problem and conventional antibiotics are failing to provide effective therapy due to resistance development thus the need for innovative strategies to combat the problem... Nanoplexes are drug nanoparticles which form complex with oppositely charged polyelectrolyte and have shown to be effective drug delivery of antibiotics. The aim of this study is toexplore the in vitromolecular pattern of vancomycin (VCM) and dextran (VCM-DXT)nanoplexes in fluorescence emission enhancement, maximized membrane disruption, decrease protein concentration and DNA concentration inMRSA for a mechanistic understanding of VCM-DXT elimination of the bacteria. The nanoplexes were characterized for their in vitro electrical conductivity, membrane disruption, protein concentration determination and DNA quantification.The in vitroelectrical conductivity of the VCM-DXT-nanoplexes demonstrated an increase in the electrical conductivity from 0.321 ± 0.01 to 0.39 ± 0.11 mS cm-1. These indicatean increase in membrane permeability of bacteria by destroying the cell membrane leading to the leakage of cellular substance in combating infectious diseases. Furthermore, the VCM-DXT-nanoplexes revealed a maximum MRSA membrane destruction and high emission enhancement intensity of the biofilm obtained from high-resolution transmission microscopy and fluorescence microscopy respectively. The VCM-DXT-nanoplexes demonstrated 3-fold and 1.98-fold decreased in protein concentration and DNA quantification respectively compared to the control. The novel VCM-DXTnanoplexes could be a promising delivery system of VCM by effectively eliminating MRSA infections and prevention of emergence of resistance. This could go a long way in preserving the potency of VCM and extending the time-lapse before the development of resistance.
Study of the clinical and microbiological profile of patients with endocarditis and cancer – A case series from Tertiary care cancer hospital in Western India
Authors: Vaidya Viplov , Dhir Aruna Alahari , Sawant Sheela , Daddi Anuprita , Mehrotra Kush
Published: March 2020

Background:

Endocarditis is rare and can be life-threatening in patients with cancer. We sought to evaluate the clinical and microbiological profile of patients of cancer who developed endocarditis.

Methods:

We retrospectively analyzed transthoracic echocardiograms done in our hospital along with the clinical data stored in computerized medical records between 2016-2018. Infective Endocarditis was diagnosed by using modified Duke criteria. Patients with valvular verrucae and sterile blood cultures were considered to have culture-negative endocarditis.

Results:

There were 10 patients of cancer who were diagnosed with endocarditis. All patients had developed endocarditis after the diagnosis of cancer. 5(50%) patients had hematological malignancy. The aortic valve was involved in 5 (50%) patients. Blood cultures were sterile in 7(70%) patients. Out of the 3 patients with positive blood cultures, 2 were positive for Klebsiella pneumoniae and 1 grew Candida tropicalis.

5 (50%) patients had concurrent pneumonia. The most common intravenous antibiotics given were cefoperazone plus sulbactam, teicoplanin, and meropenem, while most common antifungals given were caspofungin and voriconazole. The patient with Candidemia underwent surgical removal of vegetation as advised by a cardiologist. Histopathological examination and staining of the excised vegetation of this patient revealed Cryptococcus species. 6 (60%) patients developed congestive cardiac failure. 4(40%) died within 4 weeks of diagnosis of endocarditis, out of which 3 were culture-negative endocarditis.

Conclusions:

In our case series, none of the blood cultures grew gram-positive bacteria and an increased proportion of culture-negative endocarditis was noted. The mortality is high in patients of cancer with endocarditis.
Role of Climatic factors influencing Dengue incidence in central India: A model for Dengue prediction
Authors: Nigam Rishi Kumar
Published: March 2020

Introduction:

Dengue is caused an arbovirus and transmitted by Aedes mosquito. The mosquito lifecycle is influenced by various climatic factors This study was carried out to examine whether the climatic factors data can be used to predict yearly dengue cases .

Methods:

Monthly reported dengue cases and climate data for the years 2012–2016 were obtained from the Chief Medical and Health officer,Bhopal and Meteorological Department , respectively. One-way analysis of variance was used to analyse whether the climatic parameters differed significantly among seasons. Four models were developed using negative binomial generalized linear model analysis. Monthly rainfall, temperature, were used as independent variables, and the number of dengue cases reported monthly was used as the dependent variable. The first model consider data from the same month, while the other three models involved incorporating data with a lag phase of 1, 2, and 3 months, respectively.

Results:

Climatic factors, rainfall and maximum temperature were significantly correlated with monthly dengue cases. The greatest number of cases was reported during the post-monsoon period. Temperature, rainfall, and humidity varied significantly across the pre-monsoon, monsoon, and post-monsoon periods. The best correlation between these climatic factors and dengue occurrence was at a time lag of 2 months.

Conclusions:

The climate had a major effect on the occurrence of dengue infection in Bhopal city of central India. Though the prediction model had some limitations in predicting dengue cases, it could forecast possible outbreak two months in advance with considerable accuracy, and can act as early warning system.
Utilising data held within ePACT2 to monitor and influence antimicrobial prescribing within secondary care outpatient clinics
Authors: Hamilton Ryan Ashley , Grant Allister
Published: March 2020

Background

Assurance and intervention is needed around antimicrobial prescribing in secondary care outpatient settings, which has increased by 21% in 5-years. Use of NHS FP10 prescriptions impedes timely monitoring of prescribing. This project aimed to develop an efficient method for monitoring and reporting outpatient prescribing on FP10 forms.

Methods

A Microsoft Excel spreadsheet was developed to allow direct importing of antimicrobial prescribing data from ePACT2, which then automatically updates charts of prescribing activity using VLookup formulae and pivot charts. Reports were developed in Microsoft Word that directly pull updated charts from the spreadsheet described.

Results

The method allows rapid calculation and collation of DDDs and creates charts for assessing monthly antimicrobial prescribing trends. The reports highlight areas for review and action, which have driven engagement in antimicrobial stewardship across the organisation. Unexpectedly, these reports heightened nurses’ awareness of antimicrobial stewardship (AMS), who now seek reassurance on, and challenge, antimicrobial prescribing at the time of prescribing. The process takes less than 20-minutes on average (versus 3-hours previously), freeing up antimicrobial pharmacists’ time to interrogate prescribing trends and undertake clinical duties. This method also allows potentially inappropriate prescriptions to be identified and pulled from NHS BSA sooner, so that individual prescribers and teams can be targeted for intervention and reflection.

Conclusion

This method allows efficient reporting of antimicrobial prescribing, enables stewardship teams to focus interventions on prescribers and teams, and drives engagement in antimicrobial stewardship. This method could be adapted by other organisations to monitor and interrogate antimicrobial prescribing.
Predicting Cotrimoxazole-Associated Acute Kidney Injury and Hyperkalaemia
Authors: Rajput Jaikishan , Moore Luke , Mughal Nabeela , Marvin Vanessa , Hughes Stephen
Published: March 2020

Background:

Increasing antimicrobial resistance has renewed interest in older, infrequently used antimicrobials. Cotrimoxazole shows future promise; however, acute kidney injury (AKI) and hyperkalaemia are potential complications. Recognising risk factors for cotrimoxazole-associated AKI and hyperkalaemia, and quantifying the impact, are required for safe use against future antimicrobial resistance.

Method:

A single-centre retrospective observational study using electronic-healthcare records of patients prescribed cotrimoxazole was conducted. Patient risk factors were identified, and serum creatinine and potassium levels were analysed over the subsequent 21-days from prescription. Univariate and multiple logistic regression analyses were performed. The project was registered locally with the clinical governance team as service evaluation [Ref: CSS033].

Results:

Of 214 patients, 42 (20%) developed AKI and 33 (15.4%) developed hyperkalaemia. Low baseline eGFR (<60mls/min/1,73m2, OR = 7.78, 95%CI 3.57-16.13, p<0.0001) and pre-existing cardiac disorders (OR = 2.40, 95%CI 1.17-4.82, p=0.011) significantly predicted AKI. Early serum creatinine increases within 2-4 days of therapy predicted future AKI (OR = 3.65, 95%CI 1.73-7.41, p = 0.001). A low baseline eGFR also significantly predicted future hyperkalaemia (<60mls/min/1.73m2, OR = 6.80, 95%CI 3.09-15.06, p<0.0001). Low-dose cotrimoxazole (<1920mg/day) was associated with lower AKI and hyperkalaemia risk (p = 0.007 and 0.019, respectively).

Conclusions:

Cotrimoxazole-associated AKI and hyperkalaemia is frequent and dose-dependant. Renal function and pre-existing cardiac disorders should be carefully evaluated before prescribing cotrimoxazole. Serum creatinine should be monitored in the first 2-4 days of treatment to identify susceptible patients, and low-doses considered if AKI or hyperkalaemia is suspected.
Optimising the diagnosis of UTI in patients with mixed growth bacteriuria
Authors: Folaranmi Tolulope , Kirby Andrew , Harley Clare , Jolly Jim , Freeman Jane
Published: March 2020

Background: Leeds Teaching Hospitals NHS Trust (LTHT) Microbiology department report urine cultures with >1 isolate as ‘mixed growth’ (MG). The clinical significance of this remains controversial. We aimed to describe MG and explore how clinicians interpret MG reports.

Methods: Urine culture data (2018) were retrospectively collected from the LTHT laboratory information system. Urine cultures reported as MG from a one-week period in 2019 underwent further laboratory analysis. Semi-structured interviews of eight NHS clinicians were explored for emergent themes around MG using framework analysis. Clinicians were also provided with data in existing MG report formats and alternative reports including organism identities and sensitivities; and clinician propensity to diagnose/treat urinary tract infection (UTI) was noted.

Results: Of 115664 cultured specimens, 12% were MG with rates highest in patients >65yrs (19.3%, n=41760) and <1yr old (18.7%, n=2727). Of 459 isolates from 200 MG cultures, Enterococcus species (30.1%) and E. coli (27.5%) were most frequently isolated and the most frequent organism combination (24%). 65.5% of cultures contained 2 organisms, with 82.5% having at least one Enterobacteriales. Many clinicians believed MG statements represented detection of many commensal bacteria which did not represent infection. When given alternative reports including organism identities/sensitivities, (cf. report of MG only), more were likely to diagnose and treat a UTI

Conclusions: MG in urines is common. Most MGs include Enterobacteriales, an important cause of UTI. Reporting two species as MG only can be misleading, resulting in failure to treat clinically apparent infections.
A retrospective study to evaluate the epidemiology, standard of care, outcomes and resource utilization in patients with confirmed or suspected infection by a carbapenem resistant Gram-negative organism in the UK – the CARBAR study - Epidemiology of Gram negative organisms
Authors: Goldenberg Simon , Dodgson Andrew , Barlow Gavin , Parcell Benjamin , Jones Lim , Albur Mahableshwar , Wilson Peter , Hussain Abid , Enoch David A. , Marek Aleksandra , Saunders Luke , Lopes Sara , Manisero Davide , Longshaw Christopher , Tone Keiko
Published: March 2020

Background:

Antimicrobial resistance is a global threat with potentially devastating consequences and significant costs to society. Carbapenems are customarily reserved for difficult-to-treat Gram-negative (GN) infections, but resistance is increasing; hence WHO classified carbapenem-resistant (CR) strains of Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA), and Enterobacteriaceae as critical priority.

CR-GN infections have few effective treatment options, with variable outcomes and scarce clinical trial evidence. In this analysis, we describe the epidemiology of patients infected with CR-GN organisms.

Methods:

Retrospective chart review from 10 sites in UK. Adult patients admitted to hospital between April 2017-March 2018 were included if they had a confirmed GN bacterial infection and/or positive screening isolate for CR-GN bacteria colonisation. Data collection included microbiological results and patient demographics.

Results:

36,078 patients were included, representing 42,310 GN isolates, of which 3,063 (7%) were CR-GN. Mean age was 59.9 years; 60.2% were female.

The most prevalent GN species were E. coli representing 51.8% of all isolates, followed by P. aeruginosa (12.0%), and K. pneumoniae (8.7%).

Within CR-GN isolates CRPA represented 26.6%, E. coli 21.5%, and other bacteria 51.9% (including CRAB and Stenotrophomonas maltophilia).

Conclusion:

GN isolates are frequent across the UK, and 7% are CR-GN, representing a small important segment of this population. Understanding the real-world prevalence of GN and particularly CR-GN infections, where there is the highest unmet need, can help optimise antimicrobial stewardship and infection control programmes and ultimately improve overall patient’s and healthcare system’s outcomes, which is the focus of this study’s next phase.
Electronic medicine dispensing cabinet usage reporting as a tool for hospital antimicrobial stewardship
Authors: Duguid Anne , Romanes David , James Edward
Published: March 2020

Multi disciplinary antimicrobial ward rounds have been demonstrated to be effective in promoting good antimicrobial stewardship (AMS) within hospitals. The ability to review patients’ current antibiotic treatment and intervene in a timely fashion is essential in this process. Hospital Electronic Prescribing and Medicines Administration (HEPMA), where available, is an invaluable aid in this but, for many Health Boards, its introduction is still a long time in the future.

In the absence of HEPMA, other surrogates can be used, such as pharmacy stock software, to identify patients requiring AMS review e.g. for use of “alert” antibiotics. These systems would not, however, provide patient-level information from stock issues to ward areas.

This study investigated the potential of ward electronic medicine dispensing cabinets to provide patient-level data on alert antibiotic use in a hospital where HEPMA was not in use. Daily reports on “alert” antibiotic issues were sent via automated message to the Consultant Microbiologist and Antimicrobial Pharmacist. Patients’ antibiotic use was then reviewed and documented using ICNET software.

Data from AMS ward rounds over a period prior to and after the introduction of electronic cabinet reporting were analysed. A 50% increase in the identification of alert antibiotic issues was seen after the introduction of electronic cabinet reporting. Over a one month period, time for AMS intervention was reduced by an average of 8h (range 3.5-28.5h) with the use of cabinet reporting.

Electronic cabinet reporting has been shown to be a useful tool for facilitating good antimicrobial stewardship in a general hospital.
A lateral flow strip in combination with microfluidic device and polymerase chain amplification for rapid and visual detection of lymphatic filarial infection
Authors: Phuakrod Achinya , Sripumkhai Witsaroot , Jeamsaksiri Wutthinan , Pattamang Pattaraluck , Foongladda Suporn , Sarasombath Patsharaporn , Wongkamchai Sirichit
Published: March 2020

Background:

Lymphatic filariasis (LF) is a neglected tropical disease caused by the filarial nematode parasites which is transmitted by the bites of infective mosquitoes. The diagnosis of LF traditionally relies on the detection of circulating microfilariae (mf) using Giemsa-stained thick blood smears which has several limitations.

Materials and methods:

In the present study, we developed a lateral flow (LF) strip to be used in combination with a novel microfluidic device and polymerase chain reaction (PCR) for a rapid and visual detection of lymphatic filariae, Brugia malayi/ Wuchereria bancrofti infection in human blood samples.

Results:

The assay targets B. malayi HhaI gene and W. bancrofti Ssp gene. Prior to perform the assay, no DNA product clean up step required, thus, it can shorten time and reduce cost. The LF strip can detect as low as 10 pg of DNA product and no cross-reactivity with DNA of other parasites such as Gnathostoma spinigerum, cysticercisis soliumnor with DNA of other filariae i.e. Brugia pahangi, Dirofilaria immitis andD. repens.

Conclusions:

The developed LF strip shows high sensitivity and specificity, in combination with a novel microfluidic device and PCR, can be used as an alternative tool for the diagnosis of lymphatic filariasis.
Outcomes of an admission avoidance scheme for diabetic foot infections via OPAT
Authors: Atack Kelly , Waterhouse Annabelle
Published: March 2020

Background

The 2019 National Diabetes Foot Care Audit shows 2.7% of patients with a diabetic foot ulcer underwent major amputation within six months and 14% died within twelve months. Our OPAT service treats such patients referred from inpatient wards and via the limb salvage clinic as an admission avoidance scheme. A review compared outcomes between these referrals and the national data.

Methods

The OPAT database identified patients referred via an inpatient ward and the clinic. Each patient was then reviewed for each of the following criteria:

1. Was the patient alive and ulcer free at 12 weeks?

2. Had the patient had a major amputation within six months?

3. Was the patient still alive after 12 months?

Results

100 patients were reviewed; 50 referred by inpatient wards and 50 referred by the clinic as admission avoidance patients.

In both categories, 94% of patients were alive after twelve weeks, with 12% being ulcer-free in the inpatient category compared with 18% in the admission avoidance group. 6% had a major amputation within six months in the inpatient group, compared with none in the admission avoidance group. 16% of patients in the inpatient group had died within 12 months of treatment, compared with 10% of admission avoidance patients.

Discussion

OPAT patients receiving treatment for diabetic foot infections have similar outcomes to those in the national audit. No extra harm is being done to those referred to OPAT without hospital admission.
Intravenous drug use causing Enterococcus Faecalis bacteraemia, mycotic pulmonary artery aneurysm and suspected Mucormycosis
Authors: Cobb Katherine , Callaby Helen , Rae Nikolas
Published: March 2020

Background

33 year old previously fit and well lady with a history of previous drug use presented generally unwell with shortness of breath and cough.

Methods

Initial investigations demonstrated marked inflammatory response with bilateral pneumonia on chest xray. She was initially treated for severe community acquired pneumonia. On day 3 of admission blood cultures isolated Enterococcus faecalis, which was later also isolated in sputum.

Results

Transthoracic echo demonstrated no evidence of vegetations to suggest endocarditis. Despite appropriate antibiotic switch inflammatory markers increased, and a groin abscess was suspected on clinical examination leading to CT angiogram in addition to CT thorax. Imaging demonstrated left ileofemoral DVT and a large pulmonary artery aneurysm with multiple cavitating pulmonary lesions. Following discussion with cardiothoracics the patient was transferred to a cardiothoracic centre for left lower lobectomy and lingulectomy. Histopathological perioperative samples showed branching fungal hyphae within multiple blood vessels, although 18s PCR returned as negative. The patient had a good clinical response with IV Amoxicillin and antifungal therapy - Oral Posaconazole was used as she suffered an adverse reaction to liposomal Amphotericin B.

Discussion

Final impression was of mycotic pulmonary artery aneurysm caused by Enterococcus faecalis with suspected mucormycosis as result of intravenous drug use. This case highlights the increased risk of mucormycosis in people who inject drugs.
Vancomycin continuous infusion - review of use on our adult intensive care unit and establishing therapeutic loading dose
Authors: Chamurally Sheiba , Remmington Chris , Cheong Jamie
Published: March 2020

Background

Reviewing compliance to our Trust guidelines on AICU led us to investigate whether the loading dose prior to continuous infusion was sufficient to achieve therapeutic levels at first measurement.

Methods

Retrospective data was pulled (January 2011 - June 2017) from a data interrogation system (SAS Enterprise Guide) which linked patients receiving continuous infusion vancomycin at a concentration of 500mg/50ml. This was presented into Excel spreadsheets, additional headings added for data interpretation, then manipulated into pivot tables to determine objectives.

Results

In 82 courses of vancomycin continuous infusions in 70 patients, 53 received correct loading doses. 31 courses had continuous infusion started within 2 hours of loading dose finishing. 13 courses started at the correct rate. 12/13 courses had vancomycin levels taken. Only one course reached therapeutic range at the first level taken (19.5mg/kg). Of the remaining 11 courses which were out of range, 7 were titrated appropriately – 6 became therapeutic, one remained out of range and was stopped. 3 were not titrated correctly and remained out of range or not titrated at all.

Conclusion

16% (13/82) of all continuous vancomycin infusions on AICU complied with guidelines. Only one patient who received the highest weight-based loading dose of 19.5mg/kg reached therapeutic range at the first level monitored, suggesting that doses of ≥20mg/kg at loading are required.
A large-scale pragmatic automated audit of the appropriateness of antibiotics initiated for presumed community-acquired pneumonia using a novel algorithmic approach
Authors: Bow Alexander , Lilley Jessica , Santos Reem , Murphy Michael , Bedford Luke , Sander Clare , Gouliouris Theodore
Published: March 2020

Background

Audit is a fundamental part of antimicrobial stewardship, but this has traditionally been labour-intensive. The advent of fully electronic records (EPIC) at Cambridge University Hospitals (CUH) presents novel opportunities for large-scale automated data analyses and feedback. We developed and validated an algorithm to audit the appropriateness of prescriptions initiated for presumed community-acquired pneumonia (CAP).

Methods

We developed an algorithm that extracts prescription and clinical data from EPIC, calculates CURB-65 scores, and assesses the appropriateness of antibiotics with an indication of CAP against Trust guidelines based on predefined rules. Clinical data included age, gender, blood results, vital signs, NEWS-2 score, MRSA status, penicillin allergy and pregnancy status. Prescriptions were limited to 48 hours from admission. The accuracy of the algorithm was validated in a representative sample of 30 patients.

We present data on all prescriptions initiated for CAP admitted to CUH between September 2018 and June 2019.

Results

On validation, the algorithm calculated the CURB-65 score with an accuracy of 97% and correctly categorised antibiotic appropriateness in 98.5% of cases. Only 15% of patients had a CURB-65 score documented in the notes.

The algorithm evaluated 4,307 prescriptions in 2,198 patients. Appropriateness was significantly better in CURB-65 scores of 2-5 (83.7%) versus 0-1 (33.5%) largely due to over-prescription of co-amoxiclav in the latter.

Conclusion

This algorithm enables large-scale analysis of prescriptions initiated for CAP with high accuracy automating the audit cycle. An automatically calculated CURB-65 score has the potential to reduce over-prescribing of co-amoxiclav and should be evaluated in the future.
National Audit of Meningitis Management (NAMM): a National Infection Trainee Collaborative for Audit and Research (NITCAR) audit of adherence to the 2016 UK joint specialist societies’ guideline on the diagnosis and management of acute meningitis in adults
Authors: McGill Fiona , Ellis Jayne , Harvey David , Defres Sylviane , MacLachlan Eloisa , Solomon Tom , Chandna Arjun , Heydermanon Robert ,   behalf of the NAMM investigators.
Published: March 2020

Background

Bacterial meningitis has significant mortality but frontline doctors will see it infrequently. Therefore, UK guidance on meningitis in adults, with auditable standards, was revised in 2016. We undertook a national audit to assess adherence to the guidelines.

Methods

Patients with community acquired meningitis were identified through coding or laboratory data. Audit standards, including immediate management, diagnostics and treatment, were evaluated by notes review.

Results

Notes from 1472 patients with meningitis were reviewed – 309/1472 (21%) had bacterial aetiology, 615/1472 (42%) viral, 548/1472 (37%) unidentified aetiology. Only 50% of patients had blood cultures taken within one hour of admission and just 2% had a lumbar puncture (LP) within the first hour. 27% received antibiotics within one hour. Most patients received ceftriaxone or cefotaxime but only 37% of over-60s received empirical anti-listeria antibiotics. 26% of patients who had antibiotics were given adjunctive steroids. Half had CSF microscopy within two hours of LP. Less than a third had pneumococcal and/or meningococcal PCR on cerebrospinal fluid. Only 44% had an HIV test. 62% had unnecessary neuroimaging before LP. Overall mortality was 3% - 16% in pneumococcal disease and 8% in meningococcal meningitis. There was a trend toward improved survival in patients with pneumococcal meningitis who received dexamethasone [85/96 (88%)] compared to those who did not [57/73 (78%)] (p=0.066).

Conclusions

Adherence to the meningitis guidelines is inadequate, potentially compromising patient safety. Improvements in guideline dissemination, novel educational resources and clinician and patient engagement are required if we are to increase guideline adherence and improve outcome.
Empyema: do we know enough?
Authors: Hatrick Sophie , Arnold David , Hamilton Fergus
Published: March 2020

Introduction

Pleural empyema is an uncommon but serious condition defined by infected fluid in the pleural space. These patients are often given long courses of empirical broad-spectrum antibiotics as the yield from conventional culture methods is notoriously low. The literature shows that with conventional culture methods of the pleural fluid up to 40-60% of causative pathogens remain unidentified. In recent years methods such as DNA analysis have been developed in an attempt to increase identification rates of pathogens. This paper aims to review the literature to determine the additional benefit of DNA analysis methods above conventional culture of fluid in pleural empyema.

Methods

A review of the literature searching for studies investigating bacteria present in pleural fluid in patients with empyema was carried out. Studies in which adult patients had a diagnosis of empyema and where conventional culture and molecular methods were used to identify the causative bacteria were included. Descriptive statistics were used to compare the increased yield from molecular methods.

Results

Five studies which compared conventional culture techniques and molecular methods for identification of the pathogen in pleural empyema cases were identified. The mean culture-positive rate and molecular-positive rate in these studies was 37.5% (range 10-58%) and 80.0% (range 22.5-82%) respectively. All the studies concluded that molecular techniques provided a greater identification rate than conventional culture techniques.

Conclusion

Pleural empyema is often culture negative leading to broad-spectrum antibiotic use. This review shows that molecular methods significantly increase the yield of causative bacteria present in pleural fluid.