bluuebunny/crossref_metadata_2025_split huggingface dataset:
P04 Solution fundamentals are lacking: time to seek practical ways to tackle the AMR crisis in Sudan and other similar settings
Authors: Ahmed Rehab 
Published: June 2022

Abstract

Background
A flood of data is showing that the silent pandemic is no longer silent. It is already here and impacting the entire world and is particularly severe in low- and middle-income countries.

Objectives
To highlight the scarcity of data about antimicrobial resistance (AMR) in Sudan, which is now devastated by the political unrest. Simultaneously the review is calling attention to the day-to-day deterioration in the infrastructural foundation necessary to combat AMR.

Methods
The review spans different topics related to AMR. It includes data and epidemiology of antimicrobial resistance, awareness and education about AMR, awareness about immunization, healthcare infrastructure, pharmacists’ viewpoints of their current roles in the healthcare.

Results
Few data about AMR are published. Resistance is reported mostly based on phenotypic data. Huge gaps in the knowledge, awareness and the curricula are evidenced to be present even among medical and veterinary students. Inefficiency of regulatory bodies and lack of coordination between them is reported. Published data reflect a wide acceptance of immunization in children under 5 years old. Pharmacists are unsatisfied by their current jobs and are ready to participate better in healthcare.

Conclusions
The radical solutions to AMR entail building robust infrastructure for healthcare and acquiring political will, which are currently and in the foreseeable future impractical and unattainable. However, solution opportunities still exist. I see three main opportunities represented in pharmacists, immunization programmes and non-profit organizations, mainly WHO. A great deal of potential lies in the sector of pharmacists. There is a substantial number of them who are willing to contribute better to healthcare. One example is the effective engagement of pharmacists who are graduating in high qualifications and education while doing minor roles. Their engagement could be incentivized by considering the participation part of their professional growth. Contrary to the case of adults, immunization of children under 5 years is accepted and implemented largely in Sudan even in remote areas. This is the second potential solution that is worthy of investment and would pay off. WHO and similar organizations at the very least could play the role of the missing coordinator, or even better they could devise pioneering know-how programmes ready to be implemented in these countries. In these programmes, WHO will be able to attract a lot of qualified volunteers to participate in awareness and education campaigns. They also could engage higher education institutions and ministries of health.
P06 The use of procalcitonin testing to improve antibiotic stewardship in all cause respiratory admissions: a retrospective analysis
Authors: Paterson S , Carey K , Murray E M , McCarron E , Rafferty P , Smyth B , Brady A , McKeeman G , Ryan K , Kidney J , Ong G 
Published: June 2022

Abstract

Background
Improving antibiotic stewardship whilst simultaneously optimizing patient safety is a perpetually vexing clinical conundrum, which has been compounded by the current COVID-19 pandemic. Procalcitonin (PCT) measurement has previously demonstrated utility in this regard, when combined with routine clinical investigation, in certain patient populations.

Objectives
To assess whether the inclusion of PCT measurement as part of routine clinical care, instituted during a quality improvement project (QIP), increases the appropriateness of antibiotic administration.

Methods
A retrospective analysis was performed on 6 month interim data obtained from May to October 2021 during a QIP, which assessed the effect of PCT measurement on antimicrobial stewardship. All patients included had a primary diagnosis of respiratory illness and were analysed both together and as COVID-19 and non-COVID-19 subgroups to assess how often antibiotics were commenced on admission, duration of treatment and appropriateness of use. Finally, as sending microbiological samples made up part of the protocol, sample sending frequency was also studied.

Results
Thirty patients were included in both the COVID-19 and non-COVID-19 baseline subgroups who did not have PCT testing performed. Fifty-two patients were included in the PCT subgroup (27 COVID-19 positive and 25 COVID-19 negative). Following introduction of PCT testing, commencement of antibiotics on admission was reduced overall and in the COVID-19 positive subgroup (P = 0.0426 and P = 0.0446, respectively) with a significant decrease in inappropriate antibiotic prescribing in these two groups (P = 0.011 and P = 0.0157, respectively) and a trend towards reduced prescribing of AWaRe watch group antibiotics such as ceftriaxone. However, once prescribed, there was no difference in duration of antibiotic treatment or the frequency of microbiological sampling.

Conclusions
The data from this interim data analysis demonstrate that PCT measurement, when combined with routine clinical investigations in the acute respiratory setting, can be used to reduce inappropriate antibiotic prescribing. This was significantly reduced overall and in the COVID-19 positive subgroup but lost statistical significance in the COVID-19 negative subgroup, where it could be hypothesized that heterogeneity and inclusion of respiratory diseases where PCT has previously encountered difficulty in determining the presence of acute bacterial infection may be the cause. The significant effect demonstrated in the COVID-19 positive subgroup suggests particular utility in this patient population.
P12 Antibiotic prescribing in hospitalized patients with COVID-19 as a function of inflammatory markers in Wave 1 versus Wave 2: a systematic review
Authors: Chatoo Saif Abbas , Thomas-Jones Emma , Pallmann Philip , Euden Joanne 
Published: June 2022

Abstract

Background
Less than 10% of hospitalized cases in the United Kingdom during the first wave of the pandemic had bacterial coinfection, but approximately 75% were prescribed antibiotics contrary to NICE guidelines. We have evaluated the relationship between antibiotic prescribing and biomarker use, in hospitalized adult patients with COVID-19 in the UK, as synthesis defined by the pandemic timeline, particularly during ‘Wave 2’ is lacking. Clinical outcomes were compared in the context of antimicrobial stewardship. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT) and white cell count (WCC) were selected based on clinical relevance.

Methods
Studies (n = 300) dated 2019–22 were identified via EMBASE and Web of Science databases, using relevant search terms. Wave 1 and Wave 2 parameters were defined by the Office for National Statistics. Literature selection was organized by the preferred reporting items for systematic reviews and meta-analyses (PRISMA). PROSPERO registration was commenced mitigating unplanned duplication. Diagnostics, prescribing, clinical outcomes and demographics were tabulated. Ten percent of studies were cross-checked.

Results
Final selection criteria yielded 29 papers, of which only 4 were from Wave 2. Cohort and retrospective studies accounted for 69% and 80%, respectively. Heterogeneity of studies prevented a meta-analysis. Determining disease severity or coinfection was the focus of ( n= 6) studies. The papers referencing WCC (n = 12) established that leucocytosis, like elevated CRP, was an efficient marker for bacterial infections. Additionally, CRP &gt;100 mg/L was associated with increased prescribing. Another common theme was cut-off values to escalate (n = 9) or de-escalate (n = 12) prescribing. In PCT papers (n = 14), common de-escalation cut-offs were 0.25 ng/mL and 0.50 ng/mL. Lower admission PCT was associated with decreased mortality, admission duration and ICU admission rate. ESR use was unevaluable as it was only mentioned in one case study. During Wave 2, the use of immunomodulatory therapy may have contributed towards lower inflammatory markers. Hospital stays decreased while ICU duration increased. In ICU patient studies (n = 4) biomarker testing was more frequent. The higher 0.50 ng/mL PCT cut-off was employed but with higher mortality and ventilation rate.

Conclusions
More studies of Wave 2 cohorts are required. A weakness of the evidence base is that cohort study outcomes were reported in varying detail, a potential consequence of the need for rapidly published evidence. Nonetheless, PCT and CRP were demonstrated to be useful as prognosis indicators on hospital admission, and in timely antibiotic prescribing. Updated national guidelines should include standardized biomarker thresholds to improve antimicrobial stewardship.
P13 Every patient who could have OPAT, should have OPAT—the importance of data
Authors: Williams Steph , Bolton Hannah , Nye Rachel , Watson Millie , Wood Alli , Cole Ann 
Published: June 2022

Abstract

Background
Outpatient parenteral antimicrobial therapy (OPAT) has a clear role to play in optimizing antimicrobial stewardship and is listed as one of the Department of Health's five options for antimicrobial prescribing decision options to focus therapy. York and Scarborough Teaching Hospital NHSFT OPAT service has been operational since January 2019, treating over 438 patients and demonstrating year-on-year growth. Growth has been progressive, however a department vision established in 2021 stretched this to seek that ‘Every patient that could have OPAT, should have OPAT’—an ambitious target but not impossible with a robust evaluation of the service and a structured approach to scale.

Objectives
An in-depth assessment to understand the current OPAT service and to identify pathways for further expansion together with potential efficiency and productivity gains.

Methods
Working in partnership with Baxter Healthcare, a 3 month diagnostic process was undertaken with the multidisciplinary team, using a range of service and quality improvement tools to inform an in-depth assessment. A clear picture of the OPAT current state was developed through: (i) outcomes analysis; (ii) insights: pathway mapping and system flow; (iii) insights: patient experience; and (iv) insights: point of use.

Results
The assessment of OPAT services provided a clear demonstration of how the service has grown from 8.4 patients per month in 2019 to 20.8 in 2020 and 27.4 in 2021, saving over 10 500 bed-days in line with the department vision and antimicrobial stewardship team goals (Figure 1). Multiple metrics have been included demonstrating clear service expansion opportunities and growth as evidenced from an initial focus on vascular, surgical and orthopaedic patients, to now include provision for patients with diabetic foot infections, bronchiectasis and intra-abdominal infections. The service has significant peaks and troughs, impacted by a number of factors impacting capacity and flow including resource, points of referral and the ability to identify patients. The OPAT Good Practice Recommendation (GPR) Assessment Tool was utilized to review overall compliance with the BSAC OPAT GPRs and to plan further improvement initiatives.

Conclusions
Moving forward the focus is on predictability for sustainable growth creating a more consistent service, with multiple care pathways optimized to meet individual patient needs across North Yorkshire. The Baxter partnership has offered the Trust an opportunity to understand the service potential and meet their ambitious vision. Ultimately the goal is for 75% of patients in the OPAT service to be on a self-care pathway, thus releasing time to care.
P14 The antibiotic resistance profile of bacteria causing acute respiratory tract infections in Khartoum, Sudan
Authors: Faisal Shima , Suliman Mohmed A , Elnima Elamin , Ahmed Rehab 
Published: June 2022

Abstract

Background
Acute respiratory tract infections (ARTIs) are the most common indication for antibiotic prescriptions. This is associated with irrational prescription and correlated with antimicrobial resistance especially in low-income countries including Sudan. This is a cross-sectional study aimed at identifying bacterial pathogens causing ARTIs and their susceptibility to the commonly prescribed antibiotics.

Methods
Bacterial pathogens (51 isolates) were obtained from 29 ARTI patients from two hospitals in Khartoum in the time period March 2021 to March 2022. Samples were collected from each patient using both nasopharyngeal and oropharyngeal swabs. They were then cultured using blood and chocolate agar. The isolated colonies were identified using Gram staining technique, biochemical test, and selective media. Antibiotic susceptibility tests (AST) were done using the Kirby–Bauer disc diffusion susceptibility test protocol. Susceptible strains were determined following CLSI guidelines. The susceptibility of isolates was determined for different antibiotics representing the important classes including co-amoxiclav, cefixime, penicillin G, oxacillin, ceftriaxone, erythromycin, levofloxacin, ciprofloxacin and meropenem.

Results
Isolates were found to be mostly (82.3%) Gram positive (Staphylococcus aureus and Streptococcus pyogenes). Pseudomonas aeruginosa was the most abundant (17.9%) Gram-negative bacteria. S. aureus isolates were found to be 100% susceptible to levofloxacin, ciprofloxacin and meropenem. S. aureus exhibited less susceptibility to ceftriaxone (75%), and the least susceptibility to co-amoxiclav (37.5%), cefixime (31.3%), oxacillin (18.8) and erythromycin (25%). S. pyogenes isolates were found to be completely susceptible (100%) to co-amoxiclav, levofloxacin, ciprofloxacin and ceftriaxone. S. pyogenes had less susceptibility to vancomycin (92%), and the least susceptibility to cefixime (38.5%) and erythromycin (26.9%). P. aeruginosa isolates were found to be 100% susceptible to levofloxacin, ciprofloxacin and ceftriaxone, with less susceptibility to ceftriaxone (66%) and the least susceptibility to co-amoxiclav (22.2%), cefixime (33.3%), erythromycin (11.1%), vancomycin (11.1%) and oxacillin.

Conclusions
Co-amoxiclav is extensively used in Sudan empirically. The results show that S. aureus and P. aeruginosa are increasingly becoming resistant to this drug. However, S. pyogenes is still susceptible to it. Conversely resistance to erythromycin and cephalosporins is shown in all the different isolated species, however these drugs are still widely used without even culture and ASTs. Luckily, non-susceptibility to ciprofloxacin and levofloxacin was not detected here. Obviously, laboratory identification and ASTs are much needed along with surveillance programmes in hospitals. Together with rational use of antibiotics these measures will help to slow down the progress of the deadly AMR pandemic.
P18 Antimicrobial resistance patterns of Campylobacter species isolated from poultry in Mathira, Nyeri County, Kenya
Authors: Chege Edith 
Published: June 2022

Abstract

Background
Campylobacter species are zoonotic pathogens recognized as a cause of gastroenteritis in the human population and pose a major public health threat worldwide. The most important in the genus is Campylobacter jejuni, which causes diarrhoea in patients, mainly children under the age of 1 year, young adults and immunosuppressed persons. Campylobacter occurs in the gut of most animals as normal flora and is transferred to foods from the faeces during slaughter. It is acquired through consumption of undercooked poultry and other meat as well as water and unpasteurized milk. Fruits and vegetables can be contaminated from water containing faeces from birds and other animals. Campylobacter can also be transmitted through contact with dogs and cats’ faeces as well as drinking contaminated water. Campylobacter infections are common in low- and middle-income countries as well as developed countries.

Objectives
To assess the prevalence and determine the antimicrobial resistance patterns of Campylobacter spp. from poultry in Mathira Sub-County, Nyeri County.

Methods
A total of 380 cloacal swabs were collected randomly form 57 farmers in Mathira, Kenya. They were transported in sterile Amies charcoal swabs under cold chain and stored at 4°C. They were enriched in Preston broth and incubated for 24 h at 42°C, after which they were streaked onto mCCDA agar and incubated for 24 h at 42°C under microaerobic conditions generated by Campy Gen™ packs. Typical grey moist, swarming and discrete colonies were identified using MALDI-TOF. Antimicrobial susceptibility testing was done on ampicillin, tetracycline, ciprofloxacin, gentamicin, erythromycin and nalidixic acid by the disc diffusion method and disc diameters were measured and interpreted using the CLSI guidelines.

Results
In total, 272 out of 380 (71.32%) isolates were Campylobacter; 190 (50%) were C. jejuni while 81 (22) were Campylobacter coli. Resistance to ampicillin was 40% for C. coli and 30.53% for C. jejuni. Overall, 53.75% of C. coli isolates and 51.85% of C. jejuni isolates were resistant to tetracycline. We found 67.50% of C. coli were resistant to ciprofloxacin as compared with 38.42% of C. jejuni. Resistance to erythromycin for C. coli and C. jejuni was 10% and 16.935%, respectively. Finally, 65% of C. coli was resistant to nalidixic acid as compared with 38.42% of C. jejuni.

Conclusions
The study found that Campylobacter spp. show high levels of resistance to tetracyclines, ciprofloxacin and nalidixic acid and are MDR. Resistance to gentamicin and erythromycin is markedly low and these antibiotics can be reserved for treatment. Surveillance activities for AMR should be enhanced and laboratory capacity increased to support surveillance and diagnosis.
P20 Identification and detailed bio-evaluation of malabaricone B as a potent antistaphylococcal lead
Authors: Kaul Grace , Sivadas Neethu , Radhakrishnan K V , Chopra Sidharth 
Published: June 2022

Abstract

Background
The dearth of antimicrobials to treat MDR infections has led to search for novel moieties with potent activity. The most suitable compounds have been derived from mainly natural sources. In this context, the current study focused on identification and determination of antistaphylococcal activity of malabaricone B (MB), one of the naturally abundant secondary metabolites (malabaricones A–D) present in the Myristicaceae family. Malabaricones have previously been reported to possess various biological activities including antimicrobial activity but prospects of its effective utilization against Staphylococcus aureus infections in particular have not been explored in detail to the best of our knowledge.

Methods
Malabaricones (A–D) were screened against an ESKAPE pathogen panel via broth microdilution assays. The hit compounds were then tested against Vero cells via MTT assays to determine their selectivity index. As the next step, their activity against clinical drug-resistant strains was evaluated. Further, time–kill kinetics against S. aureus were determined along with the ability to synergize with approved drugs via chequerboard assays, which was further validated via combination time–kill kinetics assays. The hit compound's in vitro post-antibiotic effect (PAE) and propensity to generate resistance to S. aureus was determined. Its activity against intracellular S. aureus in a J774 macrophage model of infection and ability to eradicate pre-formed S. aureus biofilms in vitro was ascertained. Finally, the hit compound's in vivo efficacy was determined in a murine neutropenic S. aureus thigh infection model.

Results
Amongst the hits identified, MB demonstrated a potent in vitro antistaphylococcal profile including equipotent activity against clinical MDR S. aureus and Enterococcus sp. with MIC 1–2 mg/L. MB exhibited concentration-dependent bactericidal activity with complete killing at 5 × MIC within 15 min of exposure with no regrowth up to 24 h. MB also displayed PAE of ∼22 h at 10 × MIC. It also has very low propensity for generation of resistance to S. aureus ATCC 29213. MB significantly eradicated pre-formed S. aureus biofilms and reduced intracellular S. aureus in the J774 macrophage infection model as well. MB strongly synergized with gentamicin at 1 × MIC in vitro with complete killing at 24 h as compared with untreated S. aureus. MB also possessed significant in vivo activity against S. aureus at 50 mg/kg BID dose with ∼0.5 log10 cfu/g reduction in thigh compared with untreated mice.

Conclusions
MB demonstrates the potential to be further developed for infections caused by S. aureus owing to its excellent in vitro and in vivo activity.
Medroxyprogesterone acetate in reindeer bulls: testes histology, cfos activity in the brain, breeding success, and semen quality
Authors: Rowell Janice E , Blake John E , Roth Kathleen M , Sutton Courtney M , Sachse Colleen C , Cupp Andrea S , Geary Thomas W , Zezeski Abigail L , Alexander Brenda M , Ziegler Robert L , Shipka Milan P 
Published: June 2022

Abstract
A previous study reported that a 400-mg dose of medroxyprogesterone acetate (MPA) reduced male reindeer aggression and blocked development of secondary sexual characteristics but did not completely impair fertility. Here we have repeated that protocol in two separate trials. In 2017, tissues and blood samples, collected from MPA and control (CTL) reindeer bulls, euthanized at 30 and 60 d post-treatment were used to evaluate testes histology and morphometrics, cfos activity in the brain and androgen levels. While testes weight tended to decline from August to September in both groups, indices of spermatogenesis remained high. By September, indices of spermatogenesis were declining in both groups with sperm density lower (P = 0.05) in MPA compared to CTL bulls. Aug CTL bulls had the highest concentrations of androstenedione (A4) (P = 0.009) and testosterone (T) (P = 0.08), whereas these androgens were baseline in Aug MPA bulls. By September, A4 and T levels in CTL bulls declined to levels measured in MPA bulls. Cfos activity had a greater number (P = 0.02) of cfos positive neurons in the central amygdala in MPA compared to CTL bulls, suggesting a heightened fear response among the MPA bulls. In the second trial (2019), MPA-treated bulls, with (E, n = 4) and without (IE, n = 4) breeding experience, were blood sampled at key points from July through September when they were put in individual harems with estrous-synchronized cows. Concentrations of T were greatest (P &lt; 0.001) among E bulls prior to MPA treatment but 1 mo after treatment, both T and A4 were baseline in all eight reindeer. Semen collected by electroejaculation at 60 d post-MPA treatment revealed only minor differences in sperm abnormalities between E and IE bulls using both fresh and frozen/thawed semen. Only three bulls (2 E and 1 IE) sired offspring. Breeding success was not related to previous breeding experience, body weight, or bull age. The failure of some MPA bulls to breed appears to be a behavioral, not a physiological, limitation. Limited application of MPA is clearly a useful tool for managing rut-aggression in non-breeding reindeer. However, the possibility that semen could be collected from MPA-treated bulls using restraint and mild sedation rather than general anesthesia should be investigated. This could improve the quality of semen collection while enhancing the safety of both handlers and animals.