bluuebunny/crossref_metadata_2025 huggingface dataset:
Rifampicin-eluting biodegradable PLGA coatings can significantly inhibit in vitro biofilm formation for 10 weeks
Authors: Fraser Justine , McCormick Christopher , Maclean Michelle
Published: March 2020

Biofilm infection is a challenging complication of implanted medical devices due to difficulties in delivering a concentrated dose of antimicrobial to the infection site. To prevent biofilm pathogenesis, a local drug-delivery method, such as drug-eluting technology using biodegradable polymers to coat implantable devices, may be favourable.

Implantable medical-grade polyester was coated in formulations of Poly(lactic-co-glycolic acid) and rifampicin (50:50, 60:40) and placed in PBS (37°C; 120rpm). To characterise release, media was collected periodically over 10 weeks and analysed (UV-spectrophotometry; 334nm). To examine biofilm inhibition, material was removed and submerged in Staphylococcus aureus and Escherichia coli suspensions (37°C; 24hrs) to stimulate biofilm formation. Biofilms were recovered using agitation/sonication, and enumerated.

Release data revealed that both formulations had an initial burst-release phase during the first 24 hours, releasing 92% (50:50) and 88% (60:40) of their respective rifampicin loads. For both formulations, this was followed by slow-release for the remainder of the examined time, reaching 98.9% (50:50) and 97.9% release (60:40). Despite a small fraction of loaded rifampicin remaining, the formulations were able to significantly inhibit S. aureus biofilm formation (up to 99%) for 10 weeks, and E. coli biofilm formation (up to 57%) for 6 weeks.

Drug-eluting polymer technology has already seen success in medical devices, such as coronary stents, to prevent restenosis. Here it has been indicated that this technology has potential in the field of infection prevention, by demonstrating the ability to inhibit in vitro biofilm formation to a significant degree for up to 10 weeks.
Treatment Failure in a Case of Fully Susceptible Tuberculous Lymphadenitis; Time to Consider Dual Pathology
Authors: Hudson Alyssa , Jenkins Megan , Heys Izak , Moran Ed
Published: March 2020

Background

The clinical presentation of tuberculous lymphadenitis (TBL) can mimic that of other pathologies; obtaining a tissue diagnosis is therefore essential. Dual pathology can manifest as apparent treatment failure and rare cases of coexistent lymphoma have been reported.

Case description

A 54-year-old fit and well man of African-Caribbean origin presented with an 8-week history of dysphagia, breathlessness and weight loss. He was tachypnoeic and thin with right supraclavicular and axillary lymphadenopathy.

An HIV test was negative. A CT thorax demonstrated clear lung fields and a 7.2cm mediastinal soft tissue mass compressing the oesophagus and trachea.

US-guided core biopsies of a supraclavicular lymph node showed necrotising granulomatous inflammation. There was no evidence of lymphoma on immunohistochemistry. An acid-fast bacillus was seen on Wade-Fite staining.

Voractiv was commenced for suspected TBL. Tissue culture subsequently grew Mycobacterium tuberculosis. Susceptibility to treatment was confirmed by whole genome sequencing.

After two months of treatment he remained symptomatic with continued weight loss. The possibility of dual pathology was considered, and the index biopsy revisited. Steroids were commenced for a possible paradoxical reaction, resulting in some initial clinical improvement.

Ten weeks into treatment, he further deteriorated requiring artificial nutrition and tracheal stenting. Repeat CT imaging showed enlargement of the mediastinal mass, now extending into the oesophageal lumen. Oesophageal biopsy demonstrated adenocarcinoma.

Conclusions

We report a case of TBL with coexistent adenocarcinoma, which whilst rare highlights the importance of reassessment for dual pathology in cases of biopsy proven TBL that fails to respond to appropriate anti-tuberculous therapy.
Physician-initiated HIV testing leads to missed opportunities in an East London Hospital Acute Admissions Unit
Authors: Lamprianidis Konstantinos Teopoulos , Soothill Germander Sarah , Jakubowska Agnieszka , Thomas Sherine
Published: March 2020

Background

The United Kingdom National Guidelines for Human Immunodeficiency Virus (HIV) Testing 2008 suggest that an HIV test should be considered in all general medical admissions, when diagnosed HIV prevalence exceeds 2 in 1000 in the local population. We evaluated physician-initiated HIV testing rates in the Acute Assessment Unit of an East London hospital.

Methods

All acute presentations over one month were reviewed retrospectively, using electronic records. Patients with confirmed HIV were identified and the requested diagnostic HIV tests were measured. The number of patients with clinical indicator conditions for adult HIV infection, as defined in the United Kingdom National Guidelines for HIV Testing 2008, who did not receive appropriate testing, was calculated.

Results

In the cohort of 1023 patients, two patients had known HIV. 58 diagnostic HIV tests were performed, including 40 tests in patients with no clinical indicator diseases. There were five admissions with ‘AIDS-defining conditions’, all of which were pulmonary tuberculosis and four out of five (80.0%) were tested. There were 118 admissions with ‘conditions where HIV testing should be offered’, 14 of which (11.9%) were tested. All HIV tests were negative.

Conclusion

Physician-initiated HIV testing was inadequate for such a high prevalence area, even in clinical indicator diseases. Physician-initiated HIV testing should be replaced with routine opt-out HIV testing in acute medical admissions units in areas of high HIV prevalence, as suggested by BHIVA (British HIV Association) guidelines, as we progress towards ending the HIV epidemic in the United Kingdom.
Chronicle of migrant hyperinfective Strongyloides stercolaris larvae and associated bacteremia in a patient suffering from Idiopathic Thrombocytopenic Purpura
Authors: Tak Vibhor , Kolita Jitu Moni , Nag Vijaya Lakshmi , Bohra Gopal Krishna , Kumar Deepak
Published: March 2020

Background:

Strongyloidiasis is a neglected nematode infestation and can lead to hyperinfection syndrome. The onset of strongyloides hyper-infection syndrome is associated with a myriad of seemingly unrelated symptoms including diarrhoea, abdominal pain, urticaria, anaemia, sepsis and acute respiratory distress syndrome.

Case report:

A 65-year-old female patient presenting with chief complaints of nausea, vomiting, abdominal cramps, diarrhea, fever and cough and was admitted to a teaching hospital on 2nd May 2019. The patient was a diagnosed case of idiopathic thrombocytopenic purpura on Azathioprine (50mg, BD) and oral corticosteroid therapy (Prednisolone 60mg, OD) and was on treatment from the same hospital. The patient developed these symptoms after 23 days of immunosuppressive therapy. Patient was continued with previous medication along with supportive management after admission. Blood and urine sample was received in the department of Microbiology on 3rd May 2019 for culture and sensitivity testing. Urine sample was sterile after 24 hours of aerobic incubation. Escherichia coli grew in blood culture and the isolate was susceptible to gentamicin, amikacin and colistin. Stool sample was received on 6th of May 2019 for routine microscopy. With wet mount preparation of stool specimen, numerous larvae of Strongyloides stercoralis were seen. Modified Ziehl-Neelsen staining was performed and oocysts of Cryptosporidium species were also seen. Wet mount preparation of sputum sample was also performed in which few larvae of S. stercoralis were seen.

Conclusion:

As corticosteroid is the mainstay of treatment in idiopathic thrombocytopenic purpura an early diagnosis and prompt specific anti-parasitic therapy is required to eradicate these infections
Brewer’s Yeast as a cause of infective endocarditis
Authors: Hammond Robert , Aggarwal Dinesh , Hurt Will , Ferran Elena , Satta Giovanni , Abbara Aula
Published: March 2020

Background: Molecular tests are increasingly used in culture negative endocarditis and may be helpful adjuncts to diagnosis; here we report the case of Saccharomyces cerevisiae mitral valve endocarditis in an immunocompetent patient.

Case History: A previously well 63 year old man presented with a ten day history of fever, nights sweats and progressive shortness of breath. On arrival, he was in acute respiratory distress, in pulmonary oedema and had a pansystolic murmur. A transoesophageal echocardiogram showed severe mitral regurgitation and a mass on the posterior leaflet of the mitral valve. He was treated for a presumed native valve endocarditis with Amoxicillin, Flucloxacillin and Gentamicin. He had a minimally invasive mitral valve repair; a vegetation was noted. All initial cultures and serologies were negative. He improved and was discharged on ceftriaxone and doxycycline on OPAT. Results three weeks post-surgery showed a Beta D Glucan of >500pg/mL (cut off 80) and an 18S PCR on the valve positive for Saccharomyces cerevisiae. No histology was available from the vegetation and fungal cultures were negative. He was much improved at that point and received 6 weeks of voriconazole to treat invasive infection; his Beta D Glucan fell to less than 30 and he was well on follow-up.

Conclusion: Saccharomyces cerevisae is an unusual cause of an endocarditis in an immunocompetent patient. This case illustrates the importance of considering non-bacterial causes of endocarditis in such cases and the utility of molecular diagnostics as adjuncts to traditional culture techniques.
Multidrug-Resistant Vibrio species recovered from some Freshwater Resources in Southwest Nigeria: a public health concern
Authors: Adesiyan Ibukun M. , Bisi-Johnson Mary A. , Ogunfowokan Aderemi A. , Okoh Anthony I.
Published: March 2020

Globally, pathogens that cause infectious water-related diseases such as diarrhea and cholera are beginning to manifest with unusual antibiotic resistance characteristics and virulence, posing a huge threat to public health. Vibrio species are a leading cause of water-and food-borne outbreaks and is widely distributed in the water environments making it a significant threat to human health worldwide. A total of 315 Vibrioisolates recovered from different freshwater resources in southwest Nigeria were confirmed by simplex PCR using toxR gene. All confirmed isolates were tested for In vitro susceptibility to 18 antibiotics using agar disc-diffusion assay and the phenotypic tetracycline-resistant isolates were further profiled for their genotypic antimicrobial resistance determinants by PCR assay. The isolates were variously susceptible to the antibiotics tested as follows: norfloxacin 308 (98%), ciprofloxacin 293 (93%), meropenem 287 (91%), cefotaxime 279 (88%), amikacin 238 (75%). Conversely, resistance to erythromycin 300 (95%), sulphamethoxazole 297 (94%), rifampicin 289 (92%), doxycycline 260 (82%), tetracycline 237 (75%) were equally observed. Tetracycline resistance isolates were assessed for resistance determinant and the following prevalence were obtained; tetA (28), tetE (20), and tet39 (3). The MAR index across the sampling locations of 0.8 to 0.94 exceeds the threshold value of 0.2, suggesting excessive antimicrobial usage at the sample source. Our findings reveal high incidence ofVibrio species in the selected freshwater resources and also signify high resistance towards some conventionally used antibiotics. Consequently, this portends that the waters are unfit for domestic, industrial and recreational purposes and a reservoir of antibiotic resistance determinants in the environment.
Candida auris real-time PCR for surveillance of patients and environment
Authors: Taori Surabhi , Khonyongwa Kirstin , Kumarage Jeevani , Smith Melvyn
Published: March 2020

Background– Candida aurisis an emerging fungus which has caused nosocomial outbreaks worldwide. Screening for surveillance is challenging as it’s a slow grower, samples may have multiple candida spp and many commercial assays have limited accuracy. Following an outbreak in 2016, a real-time PCR was developed for rapid patient and environmental screening. Laboratory parameters, results and pitfalls from Jan 2018 to March 2019 are described.

Methods– Evaluation was performed using EQA panels and validated on clinical swabs and urine samples. Patient screening was performed in high risk clinical areas from nose, throat, axilla and groin swabs and catheter urine. Environmental screening was done in areas where transmission was detected. Positive or indeterminate samples were cultured and colonies identified on the Vitek 2 and confirmed by PHE reference laboratory.

Results–The Limit of detection was 100 organisms/ml. Sensitivity, specificity, PPV and NPV were 100.00%, 99.35%, 85.71%, and 100.00%. 4,792 urines and 10,819pooled swabs were tested. 21 colonised patients were identified in two outbreaks and two isolated transmission events. Median turn-around time for positive results was 24h30min (range 04:22-96:46h) and 143h14min (range 75-406h) for PCR and culture respectively. Urine samples did not add to the overall sensitivity of screening.C. aurisDNA was detected in 30/84 (35%) environmental swabs but C. auris isolated in only 2/84. Drawbacks of the PCR include reagent contamination seen on two occasions.

Conclusion – C. auris screening by PCR is a rapid means of detection in both patients and environment but prudent use of culture is required to help determine infectivity.
Metabolite X is a novel biomarker for sepsis diagnosis and treatment
Authors: Fitzpatrick Susan , Lambden Simon , Macias David , Puthucheary Zudin , Pietsch Sandra , Mendil Lee , McPhil Mark , Johnson Randall
Published: March 2020

Background: Sepsis develops when the initial, appropriate host response to an infection becomes amplified and subsequently dysregulated. Recent research has shown that the pathogenesis of sepsis can only partially be explained by an aberrant inflammatory response, metabolic deregulation also plays a vital role. Here we have investigated the role of a novel metabolite in sepsis pathophysiology.

Methods: Urine was obtained from an LPS mouse model of sepsis and human septic patients. A colorimetric assay and mass-spectroscopy were performed to determine the expression levels of metabolite X (mX). Furthermore, mice were implanted with radiotelemetry probes and the effect of supplementation with mX on clinical symptomology was determined. Following co-administration of LPS and mX real-time measurements of temperature, heart-rate and blood pressure were obtained.

Results: The urinary excretion of mX is significantly reduced in both a mouse model of LPS-induced sepsis, and in samples taken from human septic patients. Subsequent data showed that this is due to enhanced activation of the enzyme responsible for mX degradation. Moreover, co-administration of LPS and mX in mice modulates a number of aspects of physiological responses to sepsis, and in particular, protects against sepsis-induced hypothermia. The mechanism underlying this protective effect is due to suppressed nitric-oxide signalling.

Conclusion: Our results identify a novel role for mX in sepsis pathophysiology and suggest that this metabolite is a critical diagnostic and therapeutic target for sepsis. Future studies will fully elucidate the mechanisms underlying our observations.

mX not disclosed due to IP application but will be disclosed for presentation.
Safe, sustained reduction in meropenem and piperacillin/tazobactam use in a medical high dependency unit
Authors: Robertson Paul , Altmeyer Ursula , Hamilton Kayleigh , Rennie Natalie , Cottrell Richard , Williams Gethin
Published: March 2020

There is widespread overuse of ultra-broad spectrum antibiotics (UBSA) such as meropenem and piperacillin/tazobactam (PTZ). Reductions in their use are needed to preserve their effectiveness.

Using electronic prescribing data we recorded administrations of meropenem and PTZ per month in a 12-bed medical high dependency unit (HDU) from April 2016 to March 2019. During this time there were three interventions (an antimicrobial stewardship round began in March 2017, PTZ was removed from empirical prescribing guidelines in May 2017, and a restricted antimicrobial audit began in June 2017). The latter two interventions were prompted by a national PTZ shortage.

In 2016/17 meropenem and PTZ use was 56 and 113 daily defined doses/100 acute occupied bed days (AOBD) respectively, falling to 32 and 60 in 2017/18, and to 25 and 38 in 2018/19. This represented a 55% reduction in meropenem use and a 77% reduction in PTZ use over 2 years. The drop in use was due to both fewer patients being started on UBSA and shorter durations of treatment. The use of 4C antibiotics (clindamycin, cephalosporins, co-amoxiclav and ciprofloxacin/levofloxacin) did not increase. There was no increase in unit mortality, or change in the prevalence of ESBL-producing organisms.

We describe a multi-modal intervention that, coupled with strong clinical engagement, resulted in a safe, sustained reduction in both meropenem and PTZ use in a medical HDU, without using more 4C antibiotics. We hypothesize that “top down” policies helped reduce UBSA initiation, whereas a “bottom-up” ward-based initiative helped review and stop unnecessary use.
Utilisation of Antimicrobial Stewardship (AMS) Electronic Interventions (i-Vents) as a metric of pharmacy AMS at Cambridge University Hospitals (CUH) NHS Foundation Trust
Authors: Brown Claudia , Enoch David , Micallef Christianne
Published: March 2020

Background: The aim of the project was to identify the contribution clinical pharmacists make to antimicrobial stewardship (AMS) at CUH. The EPIC e-hospital system in place allows pharmacists to record interventions (i-Vents) electronically; these can be used as a metric of pharmacist AMS.

Method:A bespoke electronic report of all AMS i-Vents which occurred in April 2018 was generated using EPIC.Each i-Vent was categorised by type, clinical speciality, grade of pharmacist making the i-Vent and whether the i-Vent was following on from a previous one. The antimicrobials(s) mentioned in each i-Vent were also recorded.

Results:During April 2018 554 pharmacist i-Vents were recorded. I-Vent types included therapeutic drug monitoring (31%), dose optimisation (22%), course length optimisation (12%), interaction and contraindication management (2%) and patient counselling (0.2%). AMS i-Vents were recorded for patients under the care of 42 clinical specialties including neonatology (12%), diabetes and endocrinology (11%) and respiratory (8%). I-vent numbers increased with seniority of pharmacist with band 8 pharmacists making the most interventions (44%) and band 6 pharmacists making the fewest (16%). There were 645 separate references to a total of 53 individual antimicrobial agents. The top three drugs mentioned in i-Vents were vancomycin (30%), gentamicin (12%), and ciprofloxacin (8%). Follow-up i-Vents constituted 111 (20%) of all recorded i-Vents.

Conclusion:Our findings demonstrate that pharmacists contribute significantly to AMS at CUH, especially on therapeutic drug monitoring and dose-optimisation issues.We suggest that AMS i-Vents are a reliable metric for monitoring AMS pharmacist activities, related directly to patient care.
From bedside to bench – optimising the local blood culture pathway
Authors: Popoola Pelumi , Stoneham Simon , Davies Bethany
Published: March 2020

Background

Optimising the blood culture (BC) pathway is essential to ensure maximal benefits for patients. There are national standards for expected turnaround times. At our acute teaching hospital, there was limited data on this. We aimed to map the local BC pathway to identify obstacles and areas for improvement in the process.

Methods

In this prospective study, all BCs taken from adult patients in the Emergency Department (ED) on allocated days over three months were included. Study days were chosen to reflect the whole working week, including out of hours. Information was gathered from multiple stakeholders, including ED clinical staff, porters, microbiology laboratory staff and clinicians. BCs were trailed from when the sample was taken until results were reported. The time taken for each stage was compared against national standards (SMIB37).

Results

107 BCs were included in the study. Only 23% achieved the 4hr target between collection and incubation; times ranged from 50 mins–27hrs8mins. None of 43 samples taken at the weekend achieved the target. Process mapping allowed the following problems to be identified: fixed, infrequent transport by porters; delays between the general laboratory and the microbiology receptions; and delay in loading the analyser. BC bottles could not be transported via the vacuum system and the analyser was only accessible when the microbiology laboratory was open, which is not 24/7.

Conclusion

The BC pathway at the hospital fails to ensure that national standards are met. Identifying key bottlenecks impeding flow will help enable the trust to make essential changes.
Evaluation of Microbiological Sampling Practice in Community Acquired Pneumonia at a South London Trust: The Cheaper, the Better?
Authors: Owusu-Agyei Andrew , Kundu Shantanu , Goodman Anna
Published: March 2020

NICE guidelines suggest cases of community acquired pneumonia (CAP) in hospital have blood and sputum cultures and legionella and pneumococcal antigen tests be considered in specific cases. Local guidelines advise respiratory viral swabs, sputum and blood culture in specific cases and urinary antigen tests only in severe cases. We assessed the frequency and appropriateness of microbiological testing in CAP.

Methods:

The electronic records of admissions to St Thomas’ Hospital, London in January 2019 were scrutinised to identify cases of CAP. The severity of each case was categorized using CRB65 scoring. Microbiological tests and their results were analysed.

Results:

64 cases of CAP were identified. Severe disease (CRB>/= 2) was present in 31%. Respiratory viral/flu swabs were sent in 76% of cases and were positive in 39% of these cases [12 (63%) were influenza]. Sputum culture was collected in 39% of cases and revealed pathogens in 24% of these. Urinary pneumococcal antigen was sent in 7 cases of non-severe disease and 1 case of severe disease and was positive in 25% of those tested. Legionella urinary antigen tests were sent in 6 cases, only 2 of whom had reasons documented for sending the test; all were negative. Blood cultures were sent in 69% of cases (44 patients) and none revealed pathogens.

Discussion:

During the influenza season the most useful microbiological test was the respiratory viral swab. Sputum culture is a cheap test that could be used more often. Expensive legionella antigen tests were performed inappropriately.
Knowledge, Attitude, Practice and Implementation of community pharmacists role in treating tuberculosis patients in south India Region
Authors: Ganachari Madiwalayya Shivakantayya , Rangaswamy Uday Kumar
Published: March 2020

Background: Knowledge, attitude, practice and implementation of community pharmacist role in treating tuberculosis patients. Community Pharmacy education in India faces many challenges. An assessment of the challenges and opportunities of community pharmacist role in eradication of Tuberculosis in India has not been conducted.

Methods: This was a cross sectional study A one-day training was conducted in 6th may 2019 in Belagavi , Karnataka state, India. A selected sample of stake holders was invited experts Like Medical education expert in the field of tuberculosis, District Tuberculosis controller officer, Deputy Drugs controller, Assistant Drugs controller. The training Program was conducted by Dept. of Pharmacy Practice, KLE college of Pharmacy, Belagavi in association with District Tuberculosis center Belagavi and Regional office of Deputy Drugs Controller, Belagavi, India.

Results: A total of 60 community pharmacists are responded. The lowest number of correct answers were to the questions were Patients with active TB disease can infect people by talking (56.7%), TB is often spread from person to person through sex (53.3%), aware of Public Private mix (PPM) for Tuberculosis control and care (35%), Anti-TB drugs which are contraindicated in pregnancy (35%).

Conclusion: There are significant gap in knowledge, Attitude and practice on TB infection and control among community pharmacist. Proper training is essential to overcome the gap between community pharmacist and Government sector to eradicate TB by 2025 from India.
Validation and Implementation of the Roche FLOW System in a Large Routine Molecular Diagnostic Laboratory
Authors: Wilson Steve , Kirk-Granger Helen , Tanner Hannah , Lewis Clare Overton , Ratcliffe Daina , Workman Judith
Published: March 2020

Background - The PHE Public Health Laboratory, Birmingham at Heartlands hospital has an annual turn-over in excess of 750,000 specimens, 41,000 of which are processed using real-time PCR in the molecular section. In 2017, due to the age of existing instrumentation, the laboratory began a programme of replacement.

Methods - During 2017-19 the entire molecular service was replaced with a new high-throughput automated Roche FLOW system, consisting of a primary sample handler (PSU), two MagNA Pure 96 instruments, a PCR set-up unit (PSU), three 384-well LightCycler 480 II instruments and overarching FLOW software responsible for automated data handling, specimen tracking and workflow between the instruments.

Results - The bulk of the in-house developed assay repertoire, representing 34 viral, bacterial and fungal targets was re-optimised in 19 multiplexes. These were fully validated against existing molecular tests and were introduced into routine diagnostic service in June 2018. The FLOW software was successfully interfaced with the LIMS system, allowing rapid two-way communication of test requests and results. Over the following ten months, the service was expanded with an additional seven targets. The new system and assays were audited by UKAS in April 2019 and achieved accreditation to ISO:15189:2012 in August 2019.

Conclusion – The Roche FLOW system was successfully validated and introduced into routine diagnostic service and now offers significant improvements in assay performance, sample throughput and turnaround time. Details of the validation process, post-implementation modifications, trouble-shooting and lessons learnt will be of value to other diagnostic laboratories considering the introduction of this technology.
Review of antibiotic prophylaxis for the prevention of surgical site infection in low and middle income countries (LMICs)
Authors: Cooper Lesley , Sneddon Jacqueline
Published: March 2020

Background

The Scottish Antimicrobial Prescribing Group (SAPG) is supporting two hospitals in Ghana via a Fleming Fund healthcare partnership to develop antimicrobial stewardship. Initial intelligence gathering suggests that antibiotic prophylaxis to prevent surgical site infection (SSI) is suboptimal. To inform a quality improvement programme we have reviewed the evidence for use of surgical prophylaxis in LMICs including staff behaviours and attitudes.

Methods

MEDLINE, Embase, Cochrane, CINHAL and Google Scholar were searched from inception to 22 July 2019 for trials, audits, guidelines and systematic review in English. Grey literature, websites and reference lists of included studies were searched. The following data were extracted; study characteristics, interventions, outcomes and recommendations. In view of heterogeneity between studies descriptive analysis was conducted.

Results

Of 185 records screened, 26 studies related to SSI and timing of antibiotic prophylaxis in LMICs were included. The incidence of SSI is significantly higher in LMICs compared with high income countries, recording of infection surveillance data is poor and a lack of local guidelines for antibiotic prophylaxis. Several projects in Africa have reported reduction in SSI with single dose preoperative antibiotic use compared with post-operative prophylaxis and a reduction in cost and nurse time. Despite evidence to the contrary, many surgeons continue to use post-operative antibiotic prophylaxis.

Conclusion

Education to improve incidence of SSI in LMICs through appropriate antibiotic prophylaxis can be successful. Interventions must include local context and address strongly held beliefs. The establishment of local multidisciplinary teams will promote ownership and sustainability of change.
Impact of the Scottish Reduction in Antimicrobial Prescribing (ScRAP) Programme on primary care prescribing for urinary tract infection (UTI)
Authors: Sneddon Jacqueline , Thomson Anne , Malcolm William , Baxter Linsey
Published: March 2020

Introduction

The ScRAP programme was developed as a national initiative to support improvements in managing patients presenting with symptoms of UTI. The programme comprises educational content plus improvement ideas. It was implemented in one large, mainly urban, NHS board region covering 21% of the Scottish population via Prescribing Support Pharmacists working with individual GP Practices. A key aim was to reduce unnecessary antibiotic use.

Method

A facilitated learning session was delivered and all clinical and non-clinical GP Practice staff, were invited to attend. Evidence supporting best practice in managing UTI, local prescribing data and local practice was considered and discussed. The session concluded with action planning to reflect on current practice and identify areas for improvement.

National data held by NHS National Services Scotland was used to evaluate prescribing across all NHS board regions in Scotland focusing on total use of antibiotics and use of trimethoprim and nitrofurantoin which are used solely for UTI.

Results

Analysis of national prescribing data comparing the implementation region with the rest of Scotland suggests the intervention has been successful. Comparing data from prior to and for one year after the intervention period reductions for the intervention board versus the rest of Scotland were as follows: all antibiotics 7.29% vs 6.11%; trimethoprim 6.14% vs 3.73%; nitrofurantoin 3.92% vs 0.56%.

Conclusion

Quantitative evaluation provides evidence of the impact of ScRAP on prescribing rates. This suggests that improved practice has led to reduction in unnecessary use of antibiotics for acute and recurrent UTI.
Incidence of Group B Streptococcus bacteraemia in mum and newborn following antimicrobial prophylaxis- To screen or not to screen?
Authors: Hughes Stephen , Davidson Alex , Moore Luke , Mughal Nabeela
Published: March 2020

Introduction

There is no routine screening for antenatal Group B Streptococcus (GBS) carriage in the UK. However invasive GBS in newborns, whilst rare (0.57/1000 births), is associated with mortality (5%) and long-term disability (9%). Antimicrobialsperi-partum can reduce the risk of invasive infection.

Method

We undertook a retrospective observational study at a London teaching hospital to investigate the incidence of invasive GBS peri-partum in both mother and child between 1/4/16 and 31/3/19.

Results

There were 16,869 live births recorded at Chelsea & Westminster Hospital during the study period. Operative, caesarean and spontaneous delivery accounted for 16.7%, 34.9% and 48.2%; with incidence of neonatal GBS bacteraemia being 0.18%, 0.08% and 0.11%, respectively. 20 (0.12%) neonates had invasive GBS infections, with 7/20 neonates having concurrent maternal GBS bacteraemia. 34(0.22%) ladies had GBS bacteraemia peri-partum; none had GBS isolated prior to delivery. 543 women had a positive GBS clinical isolate prior to labour;69.1% received GBS prophylaxis peri-partum with no invasive GBS transmission. Despite no prophylaxis in 168/543 GBS colonised women, no invasive GBS neonatal cases were identified.

Conclusions

Our local data identifies a low prevalence (0.12%) of invasive GBS infection in newborns. Maternal GBS bacteraemia is more frequently observed and associated with concurrent newborn GBS bacteraemia. Antimicrobial prophylaxis adherence peripartum although recommended is suboptimal, even though no invasive GBS transmission was identified. All invasive GBS infections were not known to be colonised pre-delivery. The current recommendations for targeting recent GBS culture do not appear to be a sensitive predictor of invasive peri-partum GBS infection.
Modernising respiratory diagnostics: the impact of biofire FilmArray pneumonia panel plus and respiratory panel on the detection of viruses and atypical bacteria
Authors: Wearmouth Debbie , Burns Phillipa
Published: March 2020

BACKGROUND

The incidence of pneumonia is high within our local patient population and it is a significant cause of morbidity and mortality. The adoption of rapid molecular technology enables targeted clinical interventions and the initiation of appropriate antimicrobial and antiviral therapy.

METHOD

From February 2019, all lower respiratory samples submitted for microbiological analysis were examined to assess if a Pneumonia FilmArray would be a suitable investigation; indications for testing included radiological evidence of pneumonia or relevant clinical information suggesting atypical infection. Nasal pharyngeal swabs could be requested by clinicians across the hospital based on presenting signs and symptoms.

RESULTS

In total 883 nasal pharyngeal swabs and 175 lower respiratory tract samples from 927 patients were tested, 514 positive results were obtained; 450 from nasal pharyngeal swabs and 64 from lower respiratory tract samples.

Notably, two Bordetella pertussis and two Legionella pneumophiliaand five Mycoplasma pneumoniae were detected. One of the Bordetella pertussis was confirmed by culture, 9 days after the molecular result and the other case was detected in a neutropenic adult within an oncology, enabling rapif infection control intervention. Both Legionella cases were confirmed with urinary antigen testing, however neither grew on culture.

CONCLUSION

FilmArray technology enables the rapid identification of the causative agents of viral and atypical pneumonia, it is a useful adjunct to traditional testing and it enables rapid clinical and infection control intervention.
Clostridiodes difficile: Colonisation versus Infection - The importance of appropriate laboratory testing to minimise risk of overdiagnosis and overtreatment
Authors: Karcher Anne Marie , Lichota Kacsper , Lee Jennifer , Parcell Ben
Published: March 2020

Background

Clostridiodes difficile (C. difficile) colonisation rates have been reported as ranging from 4-15% in healthy adults to 4-51% in long term care facilities. Inappropriate treatment for C. difficile colonisation alters gut microbiota and can consequently result in C. difficileInfection (CDI). Laboratory testing needs to aid diagnosis while at the same time minimising risk of overdiagnosis and overtreatment.

Methods

An audit was conducted of the number of patients with indeterminate and positive results between 01.09.16 and 31.08.18 to determine the impact of Scottish National C. difficile laboratory testing and CDI case definition Guidance re-inforcement in September/October 2017. A question was also added at sample requesting stage re Pseudomembranous colitis/Toxic megacolon to ensure appropriate testing.

Results

After Guidance re-inforcement, a rapid fall in number of indeterminate results (av. 34/month to 15/month) was observed. Decrease was most marked for GP patients (av. 12/month to 3/month). There was also a decrease in the number of patients with confirmed positive results (av. 9/month to 5/month).

Conclusion

Alignment with National Guidance resulted in significant reduction in patient indeterminate and positive results and assisted clinicians in the clinical diagnosis of CDI. There was also a reduction in the number of laboratory tests and repeat tests for indeterminate results. Therefore, this alignment with National Guidance resulted in Infection Prevention and Control Team, clinical and laboratory time and cost savings.
Necrotizing Otitis Externa: Four theories behind the 15-year astronomic rise of this uncommon infection
Authors: Linton Stefan , Stapleton Emma
Published: March 2020

INTRODUCTION:

NECROTIZING OTITIS EXTERNA (NOE) IS A SEVERE, LIFE THREATENING PROPAGATING OSTEOMYELITIS OF THE SKULL BASE THAT ORIGINATES FROM A SEVERE OTITIS EXTERNA. THIS RARE CONDITION MAY NOT BE AS UNCOMMON AS ONCE UNDERSTOOD. EPIDEMIOLOGIC DATA REVEALS AN UNEXPECTED AND DRASTIC RISE IN THE NUMBER OF REPORTED CASES OVER THE LAST 15 YEARS. USING NATIONAL DATA AND PUBLISHED LITERATURE, WE EXPLORE FOUR THEORIES BEHIND THE RISE IN INCIDENCE OF THIS CONDITION.

Methods:

A quantitative descriptive study was undertaken using epidemiological data obtained from the Hospital Episode Statistics (HES) database. NOE cases reported between 2002 – 2017 were compiled and analyzed. Using these results and current evidence within the published literature, four theories were formulated and explored to explain the upward trend in incidence.

Results:

There were a total of 7,327 NOE cases reported within the 15-year time period. The majority of cases (60%) occurred in the elderly (Age 75+) with a 5:2 male predominance. Mean length of stay and mean total bed days were 16.3 and 5,019 days, respectively.

Discussion:

The number of NOE cases has increased by more than 1000% within the 15-year time period, from 123 cases in 2002 to 1,405 in 2017. We theorize that this increase maybe due to:

(1) the rising prevalence of diabetes

(2) the increase in antibiotic resistance

(3) the rising ageing population

(4) improved physician awareness of NOE
Learning to prescribe antimicrobials in Northern Ireland
Authors: McKeating Cara , O'Gorman Ciaran
Published: March 2020

Background: The appropriate use of antimicrobials has implications on individual patient care, drug resistance and worldwide public health. Learning to prescribe antimicrobials is therefore an important part of medical education. The aim of this study was to evaluate novice prescribers’ readiness to use antimicrobials, in order to design valid educational activities.

Methods: A mixed methods study was carried out amongst final year students at Queen’s University Belfast and foundation year 1 (FY1) doctors working in a Northern Ireland hospital. Data was initially collected using a survey, comprised of quantitative and qualitative elements. This was supplemented by semi-structured interviews.

Results: One hundred and fifty-eight students and eighteen doctors participated in the survey. Two students and two doctors were interviewed. Both groups appeared to feel only moderately prepared to prescribe antimicrobials. Agreement with survey statements relating to knowledge and confidence was 61% and 73% for students and FY1 doctors respectively. More focused contextual teaching and practical learning opportunities were felt to be required. Students perceived a long time gap between teaching and clinical exposure. Both groups conveyed the strong influence of the working environment and local prescribing culture. These were sometimes seen as barriers to optimal prescribing. Feedback on prescribing was felt to be useful but lacking.

Conclusion: This study suggests that medical students and foundation doctors do not feel adequately prepared to prescribe antimicrobials, which may lead them to be overly influenced by suboptimal prescribing cultures. A number of curriculum development and quality improvement initiatives are suggested as a result.
Rifampicin Induced Addisonian Crisis In a Patient With Suspected Adrenal Tuberculosis
Authors: Collas Oliver , Mahmood Hussain , McGregor Alistair
Published: March 2020

A 49-year-old Indian gentleman attended A&E reporting a three-day history of fever, rigors and lower back pain. A CT KUB incidentally revealed a left adrenal mass and widespread abdominal lymphadenopathy. A subsequent CT NCAP showed lymphadenopathy above and below the hemidiaphragm with bilateral adrenal masses. A PET scan showed avidity in these locations. A right axillary lymph node biopsy revealed granulomatous lymphadenitis with focal necrosis. No microorganisms, including acid-fast bacilli were seen on staining. His Mantoux test was positive (34mm). Given his epidemiological risks factors, positive Mantoux test and evidence of necrotising granulomas on biopsy, tuberculosis was considered the most likely diagnosis, although lymphoma remained within the differential. He commenced standard first-line anti-tuberculosis treatment. One week later he re-presented reporting fever, dyspnoea, vomiting, generalised abdominal pain and increased skin pigmentation. He was tachycardic, hypotensive and hypoglycaemic (HR 129, BP 105/73, BM 3.8). Investigations showed a marked hyponatraemia, metabolic acidosis (Na+ 115, pH 7.24) and deranged liver function tests (ALT 510). ACTH was raised (869 ng/L) and a short Synacthen test showed no rise in serum cortisol. His tuberculosis medication was held and he was treated for Addisonian crisis with intravenous hydrocortisone and oral fludrocortisone. It is likely that commencing rifampicin induced metabolism of endogenous steroid, thus precipitating the crisis. Potentially, he was already compensating for low endogenous steroid production prior to initiation of rifampicin, caused by adrenal tuberculosis. He subsequently improved and was discharged with oral hydrocortisone and fludrocortisone. His tuberculosis medications with be restarted as an Outpatient.
Predictions for the binding domain and potential new drug targets of 2019-nCoV
Authors: Zeng Zehua , Luo Zhi , Du Hongwu
Published: March 2020

An outbreak of new SARS-like viral in Wuhan, China has been named 2019-nCoV. The current state of the epidemic is increasingly serious, and there has been the urgent necessity to develop an effective new drug. In previous studies, it was found that the conformation change in CTD1 was the region where SARS-CoV bound to human ACE2. Although there are mutations of the 2019-nCoV, the binding energy of ACE2 remains high. The surface glycoprotein of 2019-nCoV was coincident with the CTD1 region of the S-protein by comparing the I-TASSER prediction model with the actual SARS model, which suggests that 2019-nCoV may bind to the ACE2 receptor through conformational changes. Furthermore, site prediction on the surface glycoprotein of 2019-nCoV suggests some core amino acid area may be a novel drug target against 2019-nCoV.
Antibody binding to native cytomegalovirus glycoprotein B predicts vaccine efficacy
Authors: Jenks Jennifer A. , Nelson Cody S. , Roark Hunter K. , Goodwin Matt , Pass Robert F. , Bernstein David I. , Walter Emmanuel B. , Edwards Kathryn M. , Wang Dai , Fu Tong-Ming , An Zhiqiang , Chan Cliburn , Permar Sallie R.
Published: March 2020

Human cytomegalovirus (HCMV) is the most common infectious cause of congenital disease and post-transplant complications worldwide, yet vaccine development remains hampered by a limited understanding of protective immune responses. We investigated humoral immune correlates of protection against HCMV acquisition elicited by the most efficacious HCMV vaccine tested to-date, soluble glycoprotein B (gB) with MF59 adjuvant (gB/MF59), which achieved ∼50% efficacy in two phase II clinical trials. Protection against primary infection correlated with high magnitude antibody binding to gB expressed on a cell surface, but not to the vaccine antigen. Further, we identified monoclonal antibodies that differentially recognized soluble and cell-associated gB, highlighting structural differences essential for protective immunity. These results indicate the importance of the native, cell-associated gB conformation in future HCMV vaccine design.

One Sentence Summary

Partially-effective HCMV gB/MF59 vaccine-elicited IgG binding to cell-associated gB correlates with protection against HCMV
Structural and Evolutionary Analysis Indicate that the SARS-CoV-2 Mpro is an Inconvenient Target for Small-Molecule Inhibitors Design
Authors: Bzówka Maria , Mitusińska Karolina , Raczyńska Agata , Samol Aleksandra , Tuszyński Jack A. , Góra Artur
Published: March 2020

The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mix-solvent molecular dynamics simulations of the main protease (Mpro) enriched by evolutionary and stability analysis of the protein. The results were compared with those for a highly similar SARS Mpro protein. In spite of a high level of sequence similarity, the active sites in both proteins show major differences in both shape and size indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, analysis of the binding site’s conformational changes during the simulation time indicates its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicates that the virus’ mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro inhibitor design.
Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13
Authors: Lv Longxian , Li Gaolei , Chen Jinhui , Liang Xinle , Li Yudong
Published: March 2020

The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3’-to-5’ exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.