Antimicrobial-resistant Pathogens Research Articles

Development and validation of a rabbit model of Pseudomonas aeruginosa non-ventilated pneumonia for preclinical drug development.

New drugs targeting antimicrobial resistant pathogens, including Pseudomonas aeruginosa, have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections. We report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with Pseudomonas aeruginosa by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression. In a rabbit model of non-ventilated pneumonia, endobronchial challenge with live P. aeruginosa strain 6206, but not with UV-killed Pa6206, caused acute respiratory distress syndrome, as evidenced by acute lung inflammation, pulmonary edema, hemorrhage, severe hypoxemia, hyperlactatemia, neutropenia, thrombocytopenia, and hypoglycemia, which preceded respiratory failure and death. Pa6206 increased >100-fold in the lungs and then disseminated from there to infect distal organs, including spleen and kidneys. At 5h post-infection, 67% of Pa6206-challenged rabbits had PaO2 <60 mmHg, corresponding to a clinical cut-off when oxygen therapy would be required. When administered at 5h post-infection, humanized dosing regimens of tobramycin and meropenem reduced mortality to 17-33%, compared to 100% for saline-treated rabbits (P<0.001 by log-rank tests). For meropenem which exhibits time-dependent bactericidal activity, rabbits treated with a humanized meropenem dosing regimen of 80 mg/kg q2h for 24h achieved 100% T>MIC, resulting in 75% microbiological clearance rate of Pa6206 from the lungs. For tobramycin which exhibits concentration-dependent killing, rabbits treated with a humanized tobramycin dosing regimen of 8 mg/kg q8h for 24h achieved Cmax/MIC of 9.8 ± 1.4 at 60min post-dose, resulting in 50% lung microbiological clearance rate. In contrast, rabbits treated with a single tobramycin dose of 2.5 mg/kg had Cmax/MIC of 7.8 ± 0.8 and 8% (1/12) microbiological clearance rate, indicating that this rabbit model can detect dose-response effects. The rabbit model may be used to help predict clinical efficacy of new antibacterial drugs for the treatment of non-ventilated P. aeruginosa pneumonia.

Development of Antibacterial Cotton Textiles by Deposition of Fe2O3 Nanoparticles Using Low-Temperature Plasma Sputtering.

Antibacterial textiles can help prevent infections from antimicrobial-resistant pathogens without using antibiotics. This work aimed to enhance the cotton fabric's antimicrobial properties by depositing Fe2O3 nanoparticles on both sides of its surface. The nanoparticles were deposited using low-temperature plasma technology in a pure oxygen atmosphere, which is environmentally friendly. The Fe2O3 nanoparticles formed clusters on the fabric surface, rather than thin films that could reduce the airflow of the textile. The optimal conditions for the nanoparticle deposition were 200 W of plasma power, 120 min of immersion time, and 5 cm of Fe cathode-textile sample distance. The received antimicrobial textile was tested and the high efficiency of developed materials were successfully demonstrated against 16 microbial strains (Gram-positive and Gram-negative bacteria and fungi).

Comparative genomics and proteomics analysis of phages infecting multi-drug resistant Escherichia coli O177 isolated from cattle faeces

The increasing prevalence of antimicrobial-resistant (AMR) pathogens has become a major global health concern. To address this challenge, innovative strategies such as bacteriophage therapy must be optimised. Genomic characterisation is a crucial step in identifying suitable phage candidates for combating AMR pathogens. The aim of this study was to characterise seven phages that infect the Escherichia coli O177 strain using a whole genome sequencing. The analysis of genome sequences revealed that these phages had linear dsDNA, with genome sizes spanning from 136, 483 to 166,791 bp and GC content varying from 35.39 to 43.63%. Taxonomically, the phages were classified under three different subfamilies (Stephanstirmvirinae, Tevenvirinae, and Vequintavirinae) and three genera (Phapecoctavirus, Tequatrovirus, and Vequintavirus) within the class Caudoviricetes. In silico PhageAI analysis predicted that all the phages were virulent, with confidence levels between 96.07 and 97.26%. The phage genomes contained between 66 and 82 ORFs, which encode hypothetical and putative functional proteins. In addition, the phage genomes contained core genes associated with molecular processes such as DNA replication, transcription modulation, nucleotide metabolism, phage structure (capsid and tail), and lysis. None of the genomes carried genes associated with undesirable traits such as integrase, antimicrobial resistance, virulence, and toxins. The study revealed high genome and proteome homology among E. coli O177 phages and other known Escherichia phages. The results suggest that the seven phages are new members of the genera Phapecoctavirus, Tequatrovirus, and Vequintavirus under the subfamilies Stephanstirmvirinae, Tevenvirinae, and Vequintavirinae, respectively.

Analysis of Blood Cultures of Patients Presenting to the Emergency Department in a Tertiary Healthcare Hospital in Mumbai

Aim and objectives: Analysis of blood cultures taken from patients attending emergency departments is an important exercise in determining the common pathogens prevalent in the region. The distribution of these infective pathogens keeps changing over time, and the rise in antimicrobial-resistant pathogens makes it difficult to routinely conduct effective empirical broad-spectrum antimicrobial therapy. This study aimed to analyse the results of blood cultures obtained from patients presenting to the Emergency Department of a Tertiary Healthcare Hospital in Mumbai and provide updated and detailed information on the distribution of causative pathogens in adult sepsis and study their antibiotic-susceptibility pattern. Materials and methods: A hospital-based prospective cross-sectional study of 121 positive blood culture reports was conducted at the Department of Emergency Medicine, Fortis Hospital Mulund, Mumbai, which included all adult (age &gt; 18 yrs) suspected sepsis patients arriving to the Emergency Department whose blood cultures were sent from the Emergency Department from January 2021 to December 2021. Results: The study showed that mean age of the study cases was 59.3 years with 59.5% cases that belonged to the elderly age group with a male predominance (56.2% males–43.8% females). Overall, Gram-negative isolates were seen in 95% cases, while Gram-positive isolates were seen in only 1.7% cases. The most common organism isolated from cases with sepsis was Escherichia coli (45.5%) followed by Klebsiella (13.2%), Salmonella (10.7%), Stenotrophomonas (7.4%) and Pseudomonas (5%). Among Gram-positive organisms, Staphylococcus aureus was the most common organism isolated (1.7%). Escherichia coli isolates showed poor sensitivity towards fluoroquinolones and cephalosporins while good sensitivity towards aminoglycosides, carbapenems and combination drugs like Cefoperazone and Sulbactam and Piperacillin and Tazobactam. These findings suggest that Gram-negative organisms are the most common isolates observed in this study, with E. coli being the predominant pathogen followed by Klebsiella. High-level antimicrobial resistance was observed in sepsis cases for commonly used antimicrobials like fluoroquinolones and cephalosporins.

Thermostable Lactonases Inhibit Pseudomonas aeruginosa Biofilm: Effect In Vitro and in Drosophila melanogaster Model of Chronic Infection

Pseudomonas aeruginosa is one of the six antimicrobial-resistant pathogens known as “ESKAPE” that represent a global threat to human health and are considered priority targets for the development of novel antimicrobials and alternative therapeutics. The virulence of P. aeruginosa is regulated by a four-chemicals communication system termed quorum sensing (QS), and one main class of QS signals is termed acylhomoserine lactones (acyl-HSLs), which includes 3-Oxo-dodecanoil homoserine lactone (3-Oxo-C12-HSL), which regulates the expression of genes implicated in virulence and biofilm formation. Lactonases, like Paraoxonase 2 (PON2) from humans and the phosphotriesterase-like lactonases (PLLs) from thermostable microorganisms, are able to hydrolyze acyl-HSLs. In this work, we explored in vitro and in an animal model the effect of some lactonases on the production of Pseudomonas virulence factors. This study presents a model of chronic infection in which bacteria were administered by feeding, and Drosophila adults were treated with enzymes and the antibiotic tobramycin, alone or in combination. In vitro, we observed significant effects of lactonases on biofilm formation as well as effects on bacterial motility and the expression of virulence factors. The treatment in vivo by feeding with the lactonase SacPox allowed us to significantly increase the biocidal effect of tobramycin in chronic infection.

Trends and Progress on Antibiotic-Resistant Mycobacterium tuberculosis and Genes in relation to Human Immunodeficiency Virus

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and tuberculosis (TB) are among the infectious diseases that cause high rates of mortality worldwide. The epidemiology of antibiotic resistance in correlation to people that live with TB and HIV has not been thoroughly investigated particularly in South Africa. Numerous cases of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) have been announced immensely worldwide. The spread and control of the MDR-TB pandemic due to unsuccessful treatment is one of the most serious public issues of concern, and this challenge is of international interest. Despite all measures that have been executed to overcome the challenge of MDR-TB in recent decades, the global MDR-TB trends have kept on accelerating with more and more people becoming victims. This is attributed to the abuse, misuse, and overuse of different antibacterial agents in human medicine, animal farms, and agricultural activities which serve as a wellspring for the evolution of antimicrobial resistance within the population. Over and above, the impetuous evolution, mutation, and the transfer of resistant genes via horizontal gene transfer are well-known contributive factors towards the antimicrobial resistance problem. Among the public health concerns in the world currently is the ever-increasing problem of antibiotic resistance which outpaces the progress of newly developed antimicrobials. The propagation of antimicrobial resistance (AMR) is even more amplified in areas where the pressure of antimicrobial resistant pathogens is elevated, and hence the population with ubiquitous HIV and AIDS is considered the hotspot. This review therefore aims to give in-depth coverage on the trends and the progress on the development of TB and HIV-resistant strains, highlight strategies to solve the problem, and accentuate the repercussions of the COVID-19 epidemic on the AMR.

2588. Burden of Mortality and Antimicrobial Resistance of Bacterial Pathogens Associated with Lower Respiratory Tract and Other Thorax Infection in United States in 2019: A Systematic Analysis

Abstract Background Detailed information about the impact of bacterial antimicrobial resistance (AMR) on Lower Respiratory Tract and other thorax Infections (LRTIs) is currently unavailable. It is important to have precise data on bacterial AMR to develop effective programs and policies for controlling AMR and to use antibiotics prudently for optimal treatment of LRTI patients. The primary objective of this research is to present extensive estimates of the mortality due to "bacterial pathogens" and its "AMR" of LRTIs in the United States in 2019. Methods Mortality data associated with bacterial antimicrobial resistance and lower respiratory tract infection (LRTI) pathogens were acquired from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) in 2019. Results In United States, there were 88089 deaths (95% uncertainty interval [UI]: 66909-117145) due to bacterial pathogens in LRIT in 2019. Highest number of deaths observed due to Staphylococcus aureus (34.04%), followed by Streptococcus pneumoniae (18.30%), Pseudomonas aeruginosa (12.48%) in LRTI in 2019. There were 10984 deaths attributed to and 46482 deaths associated with bacterial AMR in LRTI in 2019. Conclusion Bacterial pathogens causing LRTIs are a significant cause of mortality in the United States. Moreover, antimicrobial resistance (AMR) among these pathogens has become a growing concern, exacerbating the burden of LRTI-related deaths. The implementation of such measures, along with the promotion of antimicrobial stewardship, can help to mitigate the impact of LRTI-associated deaths and preserve the effectiveness of available antimicrobial agents for the future. Disclosures All Authors: No reported disclosures

2838. Clinical Application and Validation of a Predictive Antimicrobial Resistance Risk Categorization Framework for Patients with Uncomplicated Urinary Tract Infection

Abstract Background Empiric antibiotic (ABX) treatment for uncomplicated urinary tract infections (uUTIs) can be ineffective due to antimicrobial resistance (AMR). Understanding the risk of AMR using data-driven approaches can inform appropriate ABX selection. We developed an AMR pathogen risk categorization framework in E. coli caused uUTI using predictive modeling and evaluated its clinical validity. Methods Eligible females with uUTI confirmed by positive E. coli urine culture treated with nitrofurantoin (NTF), trimethoprim/sulfamethoxazole (SXT), fluoroquinolones (FQs), or beta-lactams (BLs) were identified from the Optum de-identified electronic health record data set (Oct 2015–Feb 2020). We developed predictive models using machine learning to quantify AMR probability for each ABX class. A framework with 3 risk categories (low, moderate, high) was constructed using the predicted probability (PP) of non-susceptibility (NS) (Table 1). Six patient profiles from differing risk categorizations were reviewed for clinical validity by 5 clinicians (4 medical doctors, 1 pharmacist). Results Of 87,487 eligible patients, approximately half were classified as low or high risk (44.0–49.1% across ABX classes). The proportion of patients with infections due to NS organisms was 5–12-fold higher among patients classified as high or moderate vs low risk (Figure 1). After review of the patient profiles (Table 2), clinical experts confirmed the consistency of modeled risk classification for all 6 patients with their own assessment of AMR risk across all drug classes. Patient 1 was aged 20 yrs, White, West residence, no UTI or ABX history 1 year prior to her uUTI; PP of NS was low (NTF 1.5%, SXT 16.6%, FQs 4.8%, BLs 8.4%) and was classified as low risk for all ABX classes. In contrast, patient 6 was post-menopausal, Black, Midwest residence, and had UTI episodes, prior AMR, and multiple healthcare visits 1 year prior to uUTI. She had high PP of NS (NTF 10.3%, SXT 97.2%, FQs 96.4%, BLs 48.0%) and was categorized as high risk for all ABX classes. Conclusion AMR risk varied greatly between patients. Our prediction model contextualizes patients’ AMR PP to 4 commonly prescribed ABX classes in the setting of uUTIs. Clinical application of this framework could inform appropriate empiric ABX selection for patients with uUTI. Disclosures Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support Wendy Y. Cheng, MPH, PhD, ORCID: 0000-0002-8281-2496, Analysis Group, Inc.: Wendy Y. Cheng is an employee of Analysis Group, Inc., a consulting company that received funding from GSK to conduct this study Kalé Kponee-Shovein, ScD, Analysis Group, Inc: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Fernando Kuwer, MSc, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Chi Gao, ScD, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Ashish V. Joshi, PhD, GSK: Employee|GSK: Stocks/Bonds Fanny S. Mitrani-Gold, MPH, GSK: Employee|GSK: Stocks/Bonds Patrick Schwab, PhD, GSK: Employment|GSK: Stocks/Bonds Diogo Ferrinho, PharmD, GSK: Employee|GSK: Stocks/Bonds Malena Mahendran, MS, Analysis Group, Inc.: Malena Mahendran is an employee of Analysis Group, Inc., a consulting company that received funding from GSK to conduct this study Daniel Indacochea, PhD, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Lisa Pinheiro, MFin, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Jimmy Royer, PhD, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received funding from GSK to conduct the study Madison T. Preib, MPH, GSK: Employee|GSK: Stocks/Bonds Jennifer Han, MD, GSK: Employment|GSK: Stocks/Bonds Richard Colgan, MD, GSK: Advisor/Consultant

Serovars, Virulence and Antimicrobial Resistance Genes of Non-Typhoidal Salmonella Strains from Dairy Systems in Mexico.

Salmonella isolated from dairy farms has a significant effect on animal health and productivity. Different serogroups of Salmonella affect both human and bovine cattle causing illness in both reservoirs. Dairy cows and calves can be silent Salmonella shedders, increasing the possibility of dispensing Salmonella within the farm. The aim of this study was to determine the genomic characteristics of Salmonella isolates from dairy farms and to detect the presence of virulence and antimicrobial resistance genes. A total of 377 samples were collected in a cross-sectional study from calves, periparturient cow feces, and maternity beds in 55 dairy farms from the states of Aguascalientes, Baja California, Chihuahua, Coahuila, Durango, Mexico, Guanajuato, Hidalgo, Jalisco, Queretaro, San Luis Potosi, Tlaxcala, and Zacatecas. Twenty Salmonella isolates were selected as representative strains for whole genome sequencing. The serological classification of the strains was able to assign groups to only 12 isolates, but with only 5 of those being consistent with the genomic serotyping. The most prevalent serovar was Salmonella Montevideo followed by Salmonella Meleagridis. All isolates presented the chromosomal aac(6')-Iaa gene that confers resistance to aminoglycosides. The antibiotic resistance genes qnrB19, qnrA1, sul2, aph(6)-Id, aph(3)-ld, dfrA1, tetA, tetC, flor2, sul1_15, mph(A), aadA2, blaCARB, and qacE were identified. Ten pathogenicity islands were identified, and the most prevalent plasmid was Col(pHAD28). The main source of Salmonella enterica is the maternity areas, where periparturient shedders are contaminants and perpetuate the pathogen within the dairy in manure, sand, and concrete surfaces. This study demonstrated the necessity of implementing One Health control actions to diminish the prevalence of antimicrobial resistant and virulent pathogens including Salmonella.

Antibiotic sensitivity of catheter-associated bacterial pathogens in pediatrics patients

Antimicrobial-resistant (AMR) pathogens causing Urinary Tract infection is a serious public health concern in our clinical setting. A total of 200 catheter tips were collected from the different wards (medical, surgical, urology) at the Children’s Hospital Faisalabad. Samples were streaked on nutrient agar plates and the positivity of the samples was noted after 24 hours. Positive samples were processed further for the identification of K. pneumoniae, P. aeruginosa, S. aureus, and E. coli using culture identification, microscopy, and biochemical profiling on the basis of culture characterization, microscopy, biochemical profiling, and antibiotic susceptibility testing. 76 (38%) of the samples showed growth on nutrient agar. In processed samples, the high prevalence was marked for P. aeruginosa (24/200; 12%) followed by E. coli (22/200; 11%) and S. aureus (19/200; 9.5%) while 11 K. pneumoniae isolates (5.5%) were identified in this study. In antibiotic susceptibility profiling of P. aeruginosa, the highest susceptibility was found for colistin (100%) and imipenem (70.83%) followed by gentamicin (54.17%) while the highest resistance was found for tobramycin (54.17%) followed by meropenem, ceftazidime, and cefotaxime (50%). Conclusion: Advance studies are needed to investigate the real investigations of bacterial contamination; resistance to treatment options and resistance to antibiotics are needed.

Management of diseases in a ruminant livestock production system: a participatory appraisal of the performance of veterinary services delivery, and utilization in Ghana

IntroductionSustainable livestock production remains crucial for attainment of food security globally and for safeguarding the livelihoods of many households in low- and –middle income countries. However, the high prevalence of infectious livestock diseases, coupled with inadequate provision and adoption of effective control measures, leads to reduced livestock productivity, increased animal mortalities, and emergence of antimicrobial resistant pathogens. This study sought to assess the management strategies employed by farmers for priority diseases affecting their animals and the utilization and performance of veterinary services.MethodsWe conducted the study in three districts, namely, Mion, Pru East, and Kwahu Afram Plains South Districts, which represent the main livestock production belts in Ghana. We used questionnaires in surveys, to collect pertinent data from 350 ruminant livestock farmers and 13 professional veterinary officers (VOs) in the study districts. Additionally, we conducted seven focus group discussions (FGDs) with 65 livestock farmers in the study districts. The survey data was analyzed, and we describe the distribution of the priority livestock diseases, the disease management strategies employed, and the performance of veterinary services in Ghana. We also analyzed the raw FGD transcript texts deductively based on the study objectives. To validate findings across the different datasets, we used triangulation.ResultsAlmost all the farmers (98%) reared small ruminants, with about 25% also rearing cattle. The main priority livestock diseases identified includes pestes-des-petits-ruminants and mange infection in sheep and goats, as well as contagious bovine pleuropneumonia and foot-and-mouth-disease in cattle. We found that majority (82%) of the farmers relied on treatment, while only 20% opted for vaccination services. Additionally, the veterinary system in Ghana did not adequately regulate the antimicrobial medications employed by farmers to manage diseases. Thus, in most of the cases, the medicines applied by farmers were not useful for the target diseases. Although our findings show the farmers perceived VOs to perform highly compared to informal providers on most of the attributes evaluated including medicine availability and quality, treatment effectiveness, advisory services, service affordability, and competence, only 33% utilized VOs services. The majority of the farmers (51%) used the services of informal providers, who were better in proximity and popularity with farmers.ConclusionsThe livestock sector in Ghana faces a substantial challenge due primarily to vaccine-preventable diseases. Even though VOs demonstrated superior performance on key veterinary service performance indicators, their services are underutilized by livestock farmers. Additionally, the absence of regulatory oversight by the veterinary system over antimicrobials utilized in animal production contributes to their misapplication by livestock farmers, posing a considerable risk to both public health and food security. It is thus imperative to introduce new initiatives that enhance the uptake of animal vaccines and better antimicrobial stewardship to ensure sustainable livestock production.

Association of health, nutrition, and socioeconomic variables with global antimicrobial resistance: a modelling study

Although antimicrobial use is a key selector for antimicrobial resistance, recent studies have suggested that the ecological context in which antimicrobials are used might provide important factors for the prediction of the emergence and spread of antimicrobial resistance. We used 1547 variables from the World Bank dataset consisting of socioeconomic, developmental, health, and nutritional indicators; data from a global sewage-based study on antimicrobial resistance (abundance of antimicrobial resistance genes [ARGs]); and data on antimicrobial usage computed from the ECDC database and the IQVIA database. We characterised and built models predicting the global resistome at an antimicrobial class level. We used a generalised linear mixed-effects model to estimate the association between antimicrobial usage and ARG abundance in the sewage samples; a multivariate random forest model to build predictive models for each antimicrobial resistance class and to select the most important variables for ARG abundance; logistic regression models to test the association between the predicted country-level antimicrobial resistance abundance and the country-level proportion of clinical resistant bacterial isolates; finite mixture models to investigate geographical heterogeneities in the abundance of ARGs; and multivariate finite mixture models with covariates to investigate the effect of heterogeneity in the association between the most important variables and the observed ARG abundance across the different country subgroups. We compared our predictions with available clinical phenotypic data from the SENTRY Antimicrobial Surveillance Program from eight antimicrobial classes and 12 genera from 56 countries. Using antimicrobial use data from between Jan 1, 2016, and Dec 31, 2019, we found that antimicrobial usage was not significantly associated with the global ARG abundance in sewage (p=0·72; incidence rate ratio 1·02 [95% CI 0·92-1·13]), whereas country-specific World Bank's variables explained a large amount of variation. The importance of the World Bank variables differed between antimicrobial classes and countries. Generally, the estimated global ARG abundance was positively associated with the prevalence of clinical phenotypic resistance, with a strong association for bacterial groups in the human gut. The associations between bacterial groups and ARG abundance were positive and significantly different from zero for the aminoglycosides (three of the four of the taxa tested), β-lactam (all the six microbial groups), fluoroquinolones (seven of nine of the microbial groups), glycopeptide (one microbial group tested), folate pathway antagonists (four of five microbial groups), and tetracycline (two of nine microbial groups). Metagenomic analysis of sewage is a robust approach for the surveillance of antimicrobial resistance in pathogens, especially for bacterial groups associated with the human gut. Additional studies on the associations between important socioeconomic, nutritional, and health factors and antimicrobial resistance should consider the variation in these associations between countries and antimicrobial classes. EU Horizon 2020 and Novo Nordisk Foundation.

Current Uses and Future Perspectives of Genomic Technologies in Clinical Microbiology.

Recent advancements in sequencing technology and data analytics have led to a transformative era in pathogen detection and typing. These developments not only expedite the process, but also render it more cost-effective. Genomic analyses of infectious diseases are swiftly becoming the standard for pathogen analysis and control. Additionally, national surveillance systems can derive substantial benefits from genomic data, as they offer profound insights into pathogen epidemiology and the emergence of antimicrobial-resistant strains. Antimicrobial resistance (AMR) is a pressing global public health issue. While clinical laboratories have traditionally relied on culture-based antimicrobial susceptibility testing, the integration of genomic data into AMR analysis holds immense promise. Genomic-based AMR data can furnish swift, consistent, and highly accurate predictions of resistance phenotypes for specific strains or populations, all while contributing invaluable insights for surveillance. Moreover, genome sequencing assumes a pivotal role in the investigation of hospital outbreaks. It aids in the identification of infection sources, unveils genetic connections among isolates, and informs strategies for infection control. The One Health initiative, with its focus on the intricate interconnectedness of humans, animals, and the environment, seeks to develop comprehensive approaches for disease surveillance, control, and prevention. When integrated with epidemiological data from surveillance systems, genomic data can forecast the expansion of bacterial populations and species transmissions. Consequently, this provides profound insights into the evolution and genetic relationships of AMR in pathogens, hosts, and the environment.

The Economic Value of Antimicrobial Use in Livestock Production.

(1) Introduction: Antimicrobial agents have played an important role in improving the productivity of worldwide livestock production by reducing the impact of livestock diseases. However, a major drawback of antimicrobial use is the emergence of antimicrobial-resistant pathogens in food-producing animals. To reduce the use of antimicrobials, it is important to know the economic value of the use of antimicrobials and factors that determine that economic value. (2) Results: A theoretical framework was developed to assess the economic value of antimicrobial use. Three situations were distinguished: firstly, a baseline model for a farm with a conventional production system; secondly, an extension of the baseline model that includes the impact of production system improvements; and thirdly, an extension of the baseline model that includes the impacts of risk and risk attitude. This framework shows that the economic value of antimicrobial use is negatively affected by the price of productive inputs and damage-abatement inputs, and positively affected by the output price, the input-output combination, the damage abatement effect, risk aversion and variance in profit. (3) Conclusions: The theoretical framework presented in this study shows that there are several factors that (can) affect the economic value of antimicrobial use. The knowledge about the effect of these factors can be utilized to affect the economic value of antimicrobials and, consequently, affect antimicrobial use.

Bactabolize is a tool for high-throughput generation of bacterial strain-specific metabolic models.

Metabolic capacity can vary substantially within a bacterial species, leading to ecological niche separation, as well as differences in virulence and antimicrobial susceptibility. Genome-scale metabolic models are useful tools for studying the metabolic potential of individuals, and with the rapid expansion of genomic sequencing there is a wealth of data that can be leveraged for comparative analysis. However, there exist few tools to construct strain-specific metabolic models at scale. Here, we describe Bactabolize, a reference-based tool which rapidly produces strain-specific metabolic models and growth phenotype predictions. We describe a pan reference model for the priority antimicrobial-resistant pathogen, Klebsiella pneumoniae, and a quality control framework for using draft genome assemblies as input for Bactabolize. The Bactabolize-derived model for K. pneumoniae reference strain KPPR1 performed comparatively or better than currently available automated approaches CarveMe and gapseq across 507 substrate and 2317 knockout mutant growth predictions. Novel draft genomes passing our systematically defined quality control criteria resulted in models with a high degree of completeness (≥99% genes and reactions captured compared to models derived from matched complete genomes) and high accuracy (mean 0.97, n=10). We anticipate the tools and framework described herein will facilitate large-scale metabolic modelling analyses that broaden our understanding of diversity within bacterial species and inform novel control strategies for priority pathogens.

Bactabolize is a tool for high-throughput generation of bacterial strain-specific metabolic models

Metabolic capacity can vary substantially within a bacterial species, leading to ecological niche separation, as well as differences in virulence and antimicrobial susceptibility. Genome-scale metabolic models are useful tools for studying the metabolic potential of individuals, and with the rapid expansion of genomic sequencing there is a wealth of data that can be leveraged for comparative analysis. However, there exist few tools to construct strain-specific metabolic models at scale. Here, we describe Bactabolize, a reference-based tool which rapidly produces strain-specific metabolic models and growth phenotype predictions. We describe a pan reference model for the priority antimicrobial-resistant pathogen, Klebsiella pneumoniae, and a quality control framework for using draft genome assemblies as input for Bactabolize. The Bactabolize-derived model for K. pneumoniae reference strain KPPR1 performed comparatively or better than currently available automated approaches CarveMe and gapseq across 507 substrate and 2317 knockout mutant growth predictions. Novel draft genomes passing our systematically defined quality control criteria resulted in models with a high degree of completeness (≥99% genes and reactions captured compared to models derived from matched complete genomes) and high accuracy (mean 0.97, n=10). We anticipate the tools and framework described herein will facilitate large-scale metabolic modelling analyses that broaden our understanding of diversity within bacterial species and inform novel control strategies for priority pathogens.

Metallic Nanoparticles: A Promising Arsenal against Antimicrobial Resistance-Unraveling Mechanisms and Enhancing Medication Efficacy.

The misuse of antibiotics and antimycotics accelerates the emergence of antimicrobial resistance, prompting the need for novel strategies to combat this global issue. Metallic nanoparticles have emerged as effective tools for combating various resistant microbes. Numerous studies have highlighted their potential in addressing antibiotic-resistant fungi and bacterial strains. Understanding the mechanisms of action of these nanoparticles, including iron-oxide, gold, zinc oxide, and silver is a central focus of research within the life science community. Various hypotheses have been proposed regarding how nanoparticles exert their effects. Some suggest direct targeting of microbial cell membranes, while others emphasize the release of ions from nanoparticles. The most compelling proposed antimicrobial mechanism of nanoparticles involves oxidative damage caused by nanoparticles-generated reactive oxygen species. This review aims to consolidate knowledge, discuss the properties and mechanisms of action of metallic nanoparticles, and underscore their potential as alternatives to enhance the efficacy of existing medications against infections caused by antimicrobial-resistant pathogens.

Antimicrobial Resistance in Slaughterhouses, Kenya.

Slaughterhouses are hotspots for the transmission of antimicrobial-resistant pathogens. We conducted stakeholder discussions on antimicrobial-resistant pathogens within the slaughterhouse setting. Butchers were described as powerful stakeholders; challenges included limited funding and staff, inadequate infrastructure, and limited laboratory capacity. Slaughterhouse workers understood that their work increased their risk for exposure.

In the management of febrile neutropenia; evaluation of the factors affecting the lenght of hospital stay

Aim: Febrile neutropenia (FEN) is one of the most serious and commonly seen complications of patients receiving chemotherapy for a diagnosis of hematological malignancy. FEN is an emergency condition with mortality rates reaching 40% because of an increase in antimicrobial-resistant pathogens in particular. In a situation with such high mortality rates, parameters that can predict prognosis play an important role in the approach to the patient. The aim of this study was to investigate the parameters that could affect prognosis in the follow-up of FEN. Material and Methods: The study included 58 patients hospitalised in the Hematology Clinic with a diagnosis of FEN. The patients were evaluated in respect of the recorded demographic characteristics, blood group, MASCC score, hemogram, procalcitonin, C-reactive protein (CRP), Interleukin-6 (IL-6), D-dimer, fibrinogen, pre-albumin, albumin, HbA1c, anthropometric measurements and length of stay in hospital. Results: According to the statistical analysis results, patients with a length of hospital stay of ≥14 days were determined to have a significant decrease in the MASCC score and thrombocyte count and the procalcitonin, Il-6, D-dimer values and the number of antibiotics used were higher. No significant difference was determined between the groups in respect of the other parameters. Conclusion: In the management of febrile neutropenia, the most important points are the establishment of indications for hospitalisation, rapid and early recognition of a worsening status and intervention made in the right place at the right time. Parameters with prognostic benefit will help the clinician in decision-making.

부산의 실내환경에서 분리된 항생제 내성유전자

The problem of antimicrobial resistance genes and antimicrobial resistant bacteria is a very serious problem throughout the world. Korea has recognized the importance of antimicrobial resistant pathogen and has been making efforts to solve the problem of antimicrobial resistance for a long time. However, the problem of antimicrobial resistance has not yet been solved. A total of 58 filter samples were collected from 14 hospitals, 32 nurseries, and 6 out of doors during January and May 2017. For detection of class A, C, and D β-lactamase genes, aminoglycosides, fluoroquinolones, and tetracyclines, polymerase chain reactions (PCR) were performed. Among the 58 samples, 17 isolates (78.8%) showed positive results in the PCR test, but none of the samples showed positive for aminoglycoside and fluoroquinolone gene detection primers. Therefore, this study makes us realize that we need to protect the people and animal health by monitoring antimicrobial resistant bacteria and antimicrobial resistant genes in the indoor and outdoor air.