scholarly journals 670. Precision Metagenomic (PM) Sequencing Outperforms Conventional Urine Culture in Detecting Clinically Relevant Microorganisms

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S437-S438
Author(s):  
Rita C Stinnett ◽  
Bethany Kent ◽  
Marta Mangifesta ◽  
Anagha Kadam ◽  
Heng Xie ◽  
...  

Abstract Background Morbidity from urinary tract infection (UTI) is high. Urine culture is the reference method for UTI diagnosis. Its diagnostic yield is limited as prior antibiotic use prevents growth of established uropathogens, many emerging uropathogens do not grow under routine culture conditions, and results interpretation can be subjective. Faster, more comprehensive diagnostics could help manage recurrent and/or drug-resistant infections. We evaluated the diagnostic yield of a precision metagenomic (PM) workflow for pathogen detection & antimicrobial resistance (AMR) characterization directly from urine. Methods Residual urine samples from symptomatic adults evaluated by culture & susceptibility were identified by a combination of consecutive & stratified random sampling (n=480; 79% culture positive). DNA was extracted with modifications to the Quick-DNA Urine Kit (Zymo). Libraries were generated with Illumina DNA Prep with Enrichment for clinically relevant targets (191 pathogens, 1976 AMR markers) with the Explify Urinary ID/AMR Panel (UPIP, IDbyDNA). Enriched libraries were sequenced on the NextSeq550 (Illumina) and data analyzed with the Explify UPIP Data Analysis Solution (IDbyDNA). Results For bacterial uropathogens, 94% positive agreement was observed between this PM workflow and culture. PM detected fastidious and/or anaerobic potential uropathogens in 30% and 7% of samples reported as culture-negative or positive for other bacteria, respectively. Total agreement between AMR marker detection and phenotypic resistance was 78%. Notably, PM predicted phenotypes of ESBL E. coli and K. pneumoniae (10/10), MRSA (9/9), and vancomycin-resistant E. faecium (4/5). PM also detected pathogens associated with sexually-transmitted infection (C. trachomatis, HSV) and bacterial vaginosis (G. vaginalis). PM produced complete results within 24-36 hours of sample receipt (vs culture & susceptibility: 42-72 hrs). Conclusion The sensitivity of PM for uropathogen detection was noninferior to culture (Δ = 0.05; Nam RMLE; p < 0.0005). PM predicted antimicrobial resistance phenotypes for common uropathogens and identified potential pathogens not detected by conventional culture. Future studies should assess the impact of PM-guided management on clinical outcomes. Disclosures Rita C. Stinnett, PhD, MHS, IDbyDNA (Employee) Marta Mangifesta, PhD, IDbyDNA (Employee) Anagha Kadam, PhD, IDbyDNA (Employee) Heng Xie, PhD, IDbyDNA (Employee) Stacie Stauffer, BS, IDbyDNA (Employee) Jamie Lemon, PhD, D(ABMM), IDbyDNA (Employee) Benjamin Briggs, MD, PhD, IDbyDNA (Employee) Lauge Farnaes, MD, PhD, Cardea Bio (Advisor or Review Panel member)IDbyDNA (Employee) Robert Schlaberg, MD, MPH, IDbyDNA (Consultant, Shareholder, Co-founder)

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 106
Author(s):  
Sarah A. Murray ◽  
Ashlyn C. Holbert ◽  
Keri N. Norman ◽  
Sara D. Lawhon ◽  
Jason E. Sawyer ◽  
...  

In two sequential replicates (n = 90 and n = 96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, not fed) the macrolide tylosin. Diluted fecal samples were spiral-plated on plain and antibiotic-supplemented m-Enterococcus agar. In the first replicate, tylosin significantly (p < 0.05) increased the relative quantity of erythromycin-resistant enterococci. This effect was diminished in cattle fed the DFM in conjunction with tylosin, indicating a macrolide susceptible probiotic may help mitigate resistance. A similar observed effect was not statistically significant (p > 0.05) in the second replicate. Isolates were speciated and resistance phenotypes were obtained for E. faecium and E. hirae. Susceptible strains of bacteria fed as DFM may prove useful for mitigating the selective effects of antibiotic use; however, the longer-term sustainability of such an approach remains unclear.


2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Cornelius J Clancy ◽  
Deanna J Buehrle ◽  
M Hong Nguyen

Abstract We argue that the COVID-19 pandemic will result in increased antimicrobial resistance (AMR). Broad-spectrum antibiotic use is common among hospitalized COVID-19 patients and in excess of reported secondary infection rates, suggesting unnecessary prescribing. Selection pressure is likely to be particularly intense in COVID-19 epicentres and within non-epicentre hospital units dedicated to COVID-19 care. Risk factors that increase the likelihood of hospitalization or poor outcomes among COVID-19 patients, such as advanced age, nursing home residence, debilitation, diabetes and cardiopulmonary or other underlying systemic diseases, also predispose to AMR infections. Worry for AMR emergence is heightened since first-wave COVID-19 epicentres were also AMR epicentres. Disruptive direct and indirect effects of COVID-19 globally on economic systems, governance and public health expenditure and infrastructure may fuel AMR spread. We anticipate that the impact of COVID-19 on AMR will vary between epicentres and non-epicentres, by geographic region, hospital to hospital within regions and within specific hospital units.


2016 ◽  
Vol 21 (3) ◽  
pp. 131-138 ◽  
Author(s):  
Susan Hopkins

Purpose – The purpose of this paper is to highlight the local, national and global actions from the UK to reduce the impact of antimicrobial resistance (AMR) on human health. Design/methodology/approach – Synthesis of UK government policy, surveillance and research on AMR. Findings – Activities that are taking place by the UK government, public health and professional organisations are highlighted. Originality/value – This paper describes the development and areas for action of the UK AMR strategy. It highlights the many interventions that are being delivered to reduce antibiotic use and antimicrobial resistant infections.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252407
Author(s):  
Daniel Doyle ◽  
Gerald McDonald ◽  
Claire Pratt ◽  
Zahra Rehan ◽  
Tammy Benteau ◽  
...  

Objectives Inappropriate antibiotic use contributes to antimicrobial resistance. The SpectrumTM app provides antibiotic decision support, based on local antimicrobial resistance rates. We determined the impact of regional implementation of the app on inpatient antimicrobial appropriateness, inpatient antimicrobial usage (AMU), population-based Clostridioides difficile infection (CDI) rates and cost, using a retrospective, before and after quasi-experimental design, including a one-year study period. Methods The SpectrumTM app was released to prescribers in February, 2019. We performed two one-day inpatient point prevalence surveys using the National Antimicrobial Prescribing Survey tool, six months before (June 25, 2018) and six months after (June 25, 2019) app dissemination. Inpatient AMU in Defined Daily Dose/1000 patient days and CDI incidence were compared, before and after app dissemination. Results The pre-survey included 184 prescriptions, and the post-survey included 197 prescriptions. Appropriateness was 97/176 (55.1%) pre, and 126/192 (65.6%) post (+10.5%, p = 0.051). Inpatient AMU declined by 6.6 DDD/1000 patient days per month, and CDI declined by 0.3 cases per month. Cost savings associated with reduced AMU were $403.98/bed/year and associated with reduced CDI were $82,078/year. Conclusion We observed improvement in antimicrobial stewardship indicators following SpectrumTM implementation. We cannot determine the cause of these improvements.


2016 ◽  
Vol 56 (4) ◽  
pp. 205 ◽  
Author(s):  
Elfrida A. Rachmah ◽  
Maftuchah Rochmanti ◽  
Dwiyanti Puspitasari

Inappropriate use of antibiotics may lead to antimicrobial resistance. In 2012, Dr. Soetomo Hospital conducted training for pediatric residents on the proper use of antibiotics to limit antimicrobial resistance.Objective To evaluate the impact of a rational, antibiotic-use training program for pediatric residents on their antibiotic prescriptions for patients with typhoid fever.Methods A cross-sectional, analytic study was conducted. We collected data from children with typhoid fever who were hospitalized in Dr. Soetomo Hospital, pre- and post-training on antibiotic prescriptions. Children with other known bacterial infections or who were discharged on request were excluded. Antibiotic prescriptions were evaluated using Gyssens algorithm based on the local protocol. Chi-square test was used to compare the quality of antibiotic prescriptions, before (year 2012) and after (year 2013) the training.Results Forty-nine patients with 67 prescriptions in 2012 and 34 patients with 48 prescriptions in 2013 fulfilled the inclusion criteria. Patients’ ages ranged from 1-18 years. Diagnoses of uncomplicated and complicated typhoid were found in 74% and 26% of subjects, respectively. First line (chloramphenicol, thiamphenicol, ampicillin, trimetroprim and sulfametoxazol) and second line (ceftriaxone and cefixime) use were 72% and 28%, respectively. All patients were discharged in good condition. Appropriate use of antibiotics was noted in 61% of subjects in 2012 and in 81% of subjects in 2013 (P=0.036). The most common type of error in 2012 and 2013 was dosage imprecision (25% and 17%, respectively).Conclusion Training on appropriate use of antibiotics significantly improved the quality of antibiotics prescribed in children with typhoid fever in Dr. Soetomo Hospital.


2021 ◽  
Vol 83 (4) ◽  
Author(s):  
Christopher W. Lanyon ◽  
John R. King ◽  
Dov J. Stekel ◽  
Rachel L. Gomes

AbstractThe ecological and human health impact of antibiotic use and the related antimicrobial resistance (AMR) in animal husbandry is poorly understood. In many countries, there has been considerable pressure to reduce overall antibiotic use in agriculture or to cease or minimise use of human critical antibiotics. However, a more nuanced approach would consider the differential impact of use of different antibiotic classes; for example, it is not known whether reduced use of bacteriostatic or bacteriolytic classes of antibiotics would be of greater value. We have developed an ordinary differential equation model to investigate the effects of farm practice on the spread and persistence of AMR in the dairy slurry tank environment. We model the chemical fate of bacteriolytic and bacteriostatic antibiotics within the slurry and their effect on a population of bacteria, which are capable of resistance to both types of antibiotic. Through our analysis, we find that changing the rate at which a slurry tank is emptied may delay the proliferation of multidrug-resistant bacteria by up to five years depending on conditions. This finding has implications for farming practice and the policies that influence waste management practices. We also find that, within our model, the development of multidrug resistance is particularly sensitive to the use of bacteriolytic antibiotics, rather than bacteriostatic antibiotics, and this may be cause for controlling the usage of bacteriolytic antibiotics in agriculture.


2021 ◽  
Vol 8 ◽  
Author(s):  
Carlota Gudiol ◽  
Adaia Albasanz-Puig ◽  
Guillermo Cuervo ◽  
Jordi Carratalà

Sepsis is a frequent complication in immunosuppressed cancer patients and hematopoietic stem cell transplant recipients that is associated with high morbidity and mortality rates. The worldwide emergence of antimicrobial resistance is of special concern in this population because any delay in starting adequate empirical antibiotic therapy can lead to poor outcomes. In this review, we aim to address: (1) the mechanisms involved in the development of sepsis and septic shock in these patients; (2) the risk factors associated with a worse prognosis; (3) the impact of adequate initial empirical antibiotic therapy given the current era of widespread antimicrobial resistance; and (4) the optimal management of sepsis, including adequate and early source control of infection, optimized antibiotic use based on the pharmacokinetic and pharmacodynamics changes in these patients, and the role of the new available antibiotics.


2019 ◽  
Vol 58 (11-12) ◽  
pp. 1291-1301 ◽  
Author(s):  
Leslie Grammatico-Guillon ◽  
Lukman Abdurrahim ◽  
Kimberley Shea ◽  
Pascal Astagneau ◽  
Stephen Pelton

This review of pediatric antibiotic stewardship programs (ASPs) summarized the antibiotic prescribing interventions and their impact on antibiotic use and antimicrobial resistance. We reviewed studies of pediatric ASP, including the search terms “antimicrobial stewardship,” “antibiotic stewardship,” “children,” and “pediatric.” The articles’ selection and review were performed independently by 2 investigators, according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Twenty-one studies were included, from the past 15 years, increasing after the 2007 IDSA (Infectious Diseases Society of America) guidelines for ASP with a large variability of the programs, and the virtual exclusive focus on inpatient settings (90%): 16 formalized ASP and 5 non-ASP actions. A reduction in antibiotic prescribing in ASP has been demonstrated in the studies reporting pediatric ASP, but only one ASP showed a significant impact on antimicrobial resistance. However, the impact on antibiotic consumption in pediatrics demonstrated the important contribution of these strategies to improve antibiotic use in children, without complications or negative issues.


Author(s):  
Johan Vekemans ◽  
Mateusz Hasso-Agopsowicz ◽  
Gagandeep Kang ◽  
William P Hausdorff ◽  
Anthony Fiore ◽  
...  

Abstract The growing burden of antimicrobial-resistant (AMR) microbes constitutes a significant global threat. Vaccines are effective tools to prevent infections could help to control and prevent AMR. In this Viewpoint we present an Action Framework for vaccines to contribute fully, sustainably and equitably to the prevention and control of AMR by preventing infections and reducing antimicrobial use. The document identifies a series of priority actions in three areas: expanding the use of licensed vaccines to maximize impact on AMR, developing new vaccines that contribute to the prevention and control of AMR, and expanding and sharing knowledge about the impact of vaccines on AMR. The objective of this document is to support an alignment of activities among international vaccine and AMR partners, and structure and articulate key priority actions.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
M Moffatt ◽  
M Wasserman

Abstract Background Antimicrobial resistance (AMR) is a critical issue in global health causing approximately 1 million annual deaths. Vaccines are essential in addressing AMR as they reduce resistant strains and prevent development of resistance by preventing spread of disease and resulting antimicrobial use. This analysis evaluates the impact the 13-valent pneumococcal conjugate vaccine (PCV13) has had on dispensed antibiotic prescriptions (DAP) due to otitis media (OM), one of the largest drivers of DAP globally. Methods An Excel-based model was developed to estimate number of infants vaccinated with PCV13, and the associated reduction in OM cases in children &lt;5 since 2010. OM cases averted were based on a global meta-analysis and estimated cases averted were applied to infants vaccinated by country. DAP avoided were estimated assuming 90% of OM cases were prescribed an antibiotic. We then compared our modelled estimates to metrics measuring number needed to vaccinate to prevent DAP from any outcome. Results Over the past 10 years, we estimated 286,54m infants were vaccinated with PCV13, with 158,33m OM cases and as many as 142,49m DAP avoided globally. By WHO region, reductions in OM rates and DAP respectively are estimated to have been; Africa and Eastern Mediterranean (103,05m; 92,74m), South-East Asia and Western Pacific (8,82m; 7,94m), Europe (20,70m; 18,63m) and Americas (25,76m; 23,18m). Using rates from the literature of 0,20 to 1,79 total DAP avoided per child vaccinated, results ranged from to 71,63m to 511,68m. Conclusions PCV13 use has resulted in substantial reductions in OM and DAP. As we focus on OM in children &lt;5, results underestimate the full impact of PCV13 on DAP as vaccine impact on other pneumococcal diseases and adults through herd effect are not included. Recognition of the role of vaccination in addressing AMR burden is an opportunity to encourage patients, providers and healthcare systems to continually prioritize vaccination in public health efforts. Key messages Over the past 10 years, PCV13 has led to considerable reductions in dispensed antibiotic prescriptions globally, highlighting the importance of prioritizing vaccination in global healthcare systems. Our findings illustrate how vaccines can play an essential role in reducing the global burden of antimicrobial resistance through reduction of antibiotic use.


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