Resistant Bacterial Pathogens Research Articles

Identifying virulence factors using graph transformer autoencoder with ESMFold-predicted structures

With the increasing resistance of bacterial pathogens to conventional antibiotics, antivirulence strategies targeting virulence factors (VFs) have become an effective new therapy for the treatment of pathogenic bacterial infections. Therefore, the identification and prediction of VFs can provide ideal candidate targets for the implementation of antivirulence strategies in treating infections caused by pathogenic bacteria. Currently, the existing computational models predominantly rely on the amino acid sequences of virulence proteins while overlooking structural information. Here, we propose a novel graph transformer autoencoder for VF identification (GTAE-VF), which utilizes ESMFold-predicted 3D structures and converts the VF identification problem into a graph-level prediction task. In an encoder-decoder framework, GTAE-VF adaptively learns both local and global information by integrating a graph convolutional network and a transformer to implement all-pair message passing, which can better capture long-range correlations and potential relationships. Extensive experiments on an independent test dataset demonstrate that GTAE-VF achieves reliable and robust prediction accuracy with an AUC of 0.963, which is consistently better than that of other structure-based and sequence-based approaches. We believe that GTAE-VF has the potential to emerge as a valuable tool for assessing VFs and devising antivirulence strategies.

Identification of Diverse Multiple Drugs Resistant Bacterial Pathogens using Microscan Panel

Bacterial isolates from clinical sources have increased resistance to antimicrobial agents available and routinely used in developing countries like Ethiopia. One of the control measures of antimicrobial resistance is to know the susceptibility of pathogenic bacteria from clinical specimens and treat patients accordingly. Therefore the objective of the present study is to isolate bacterial pathogens from different clinical specimens and determine their antimicrobial susceptibility patterns. Clinical samples (urine, blood, pus and discharges from different body sites were cultured and isolation of bacterial pathogens were done following standard bacteriological methods using media recommended by Cheesbrough. Identification of bacterial pathogens and antimicrobial susceptibility tests were done using Micro Scan Identification Panel method. The Panels were read by Micro Scan Auto Scan 4 reader after incubating for 18 to 24 hours at 35o c aerobically. The retrospective data of microbiological culture and antimicrobial susceptibility test results were analysed. A total of 995 clinical specimens were cultured at Bethzatha Bacteriology Lab., Bethzatha Hospital, from May 2021 to February 2022. The most frequent specimens were, urine 87 (32%), blood 77(28%), pus and discharges from different body sites 65(24%). Out of these, 273(27%) yielded different bacterial pathogens. The most dominant gram negative bacterial isolates from urine samples 43/87(49%), 6/87(7%), 7/87(8%) were E. coli, Acinetobacter and Klebsiella spp, respectively in that order. Klebsiella pneumoniae 12/77 (16%) were most frequently isolated from blood culture followed by diverse coagulase negative Staphylococci (CoNS) 26/77 (33.7%) and S. aureus 15/77(19.5%). The most frequent 20/65(31%) isolates from pus and discharges were S. aureus followed by 12/65(18.5%) CoNS. In the present study, most bacterial isolates from different clinical samples were multiply resistant to ampicillin, amoxicillin, trimethoprim sulphametoaxzole, levofloxacillin and ampicillin-sulbactam. On the other hand the most frequent Gram negative bacteria, E.coli and Klebsiella pneumonia were most susceptible to amikacin and ertapenem, and the gram positive isolates, S. aureus were most susceptible to levofloxacillin and gentamicin; whereas coagulase negative staphylococci (CoNS) were most susceptible to gentamicin, tecioplanin, rifampicin, vancomycin, daptomycin. Therefore clinicians should be guided by antimicrobial susceptibility test. In the absence of antimicrobial susceptibility test we suggest that the above mentioned drugs to be most appropriate for empirical treatment in the study hospitals and health settings in Addis Ababa. Furthermore critical measures need to be taken to curb the increasing spread of AMR bacteria.

A Review on Antibiotic Resistance in Bacterial Pathogens

Human health has been greatly impacted by the use of antibiotics, which have become essential in modern medicine. The treatment of bacterial infections with antibiotics decreased childhood mortality and raised life expectancy. Global public health is seriously threatened by antibiotic resistance. The multi-drug resistance (MDR) pandemic has spread quickly throughout many nations, with some instances going untreated. This has led to greater mortality rates, longer hospital stays, increased medical expenditures, and more. The primary culprits behind nosocomial infections are thought to be a variety of multidrug-resistant (MDR) such as A. baumannii, Pseudomonas aeruginosa, Enterobacteria that produces extended-spectrum beta-lactamase (ESBL), and carbapenem-resistant CRE. The most prevalent bacterial pathogens have been identified as Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), according to recent reports. The primary factors in the development of antibiotic resistance are the subject of this review.

PREVALENCE OF BLATEM, BLASHV, AND BLACTX-M GENES AMONG ESBL-PRODUCING ESCHERICHIA COLI ISOLATED FROM THE BLOOD SAMPLES OF ICUS PATIENTS OF UNIVERSITY HOSPITALS IN SANA'A CITY, YEMEN

Aim and Objective: With the emergence of organisms such as Enterobacteriaceae that produce extended-spectrum β-lactamase (ESBL), which are resistant to multiple medications (multidrug-resistance), concerns about how best to treat infections have significantly increased. The current study examined the molecular features of ESBL in clinical isolates of Escherichia coli that resulted in bloodstream infections as well as the pattern of antibiotic resistance to gather useful data on the infection's epidemiology among Yemeni ICU patients. Subjects and methods: A cross-sectional study was conducted on sepsis patients admitted in intensive care units at four hospitals in Sana'a, Yemen, between January, 2021 and April, 2022. Blood cultures were used on patients suspected of having sepsis. Standard laboratory procedures were then used to isolate and identify possible bacterial infections, and the disk diffusion method was used to test for microbial susceptibility. All strains were tested for Extended Spectrum Beta-Lactamase (ESBL) production using the Modified Double Disc Synergy Test (MDDST). Following analysis, polymerase chain reaction, β-lactamase genes (blaTEM, blaSHV, and blaCTX-M) were identified. Results: The results of the conventional PCR experiment revealed that 33.3% of the blaCTX-M genes, 0.0% of blaSHV, and 100% of blaTEM were present in the strains of ESBL-producing E. coli that were collected. It was discovered that the E. coli isolates' patterns of antibiotic resistance to 23 different antibiotics differed greatly. The bulk of the E. coli isolates were found to be multi-drug resistant (MDR). Furthermore, MDR characteristics were observed in 85% of E. coli isolates. Conclusion: Control and surveillance of antibiotic resistance depend on an understanding of the resistance genes and patterns of antimicrobial resistance of bacterial pathogens within a given geographic area. The current study's findings showed that MDR was very common. According to the current study's findings, TEM was significantly more common than other ESBL gene types. Peer Review History: Received: 7 November 2023; Revised: 12 December; Accepted: 6 January 2024, Available online: 15 January 2024 Academic Editor: Dr. A.A. Mgbahurike, University of Port Harcourt, Nigeria, amaka_mgbahurike@yahoo.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewers: Dr. Rola Jadallah, Arab American University, Palestine, rola@aauj.edu Dr. Wadhah Hassan Ali Edrees, Hajja University, Yemen, edress2020@gmail.com

Transfer and accumulation of antibiotic resistance genes and bacterial pathogens in the mice gut due to consumption of organic foods

Over the last few decades, organic food demand has grown largely because of increasing personal health concerns. Organic farming introduces antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) into foods. However, potential effects of organic foods on the gut microbiome and ARGs have been overlooked. Using high-throughput quantitative PCR and 16S rRNA high-throughput sequencing technology, we examined 132 ARGs from major classes, eight transposase genes, universal class I integron-integrase gene (intI), clinical class I integron-integrase gene (cintI), and the bacterial community in mouse gut after 8 weeks with an either organic or inorganic lettuce and wheat diet. A total of 8 types of major ARGs and 10 mobile genetic elements (MGEs) were detected in mice gut, including tetracycline, multidrug, sulfonamide, aminoglycoside, beta-lactamase, chloramphenicol, MLSB and vancomycin resistance genes. We found that abundance and diversity of ARGs, mobile gene elements, and potential ARB in the gut increased with time after consumption of organic foods, whereas no significant changes were observed in inorganic treated groups. Moreover, MGEs, including IS613, Tp614 and tnpA_03 were found to play an important role in regulating ARG profiles in the gut microbiome following consumption of organic foods. Importantly, feeding organic food increased the relative abundance of the potentially antibiotic-resistant pathogens, Bacteroides and Streptococcus. Our results confirm that there is an increasing risk of ARGs and ARB in the gut microbiome, which highlights the importance of organic food industries taking into account the potential accumulation and transmission of ARGs as a risk factor.

Gut Microbiome Derived Lactic Acid Bacteria (GM-d-LAB) from Dwarf Goats (Capra aegagrus hircus) Inhibit the Resident Multiple Antibiotics Resistance Bacterial pathogens

Background: The global health threat posed by antimicrobial resistance (AMR) has created an urgent need for developing alternative treatment methods. Probiotics, especially Lactic Acid Bacteria (LAB), are gaining interest in this context, as they demonstrate health-enhancing effects and potent antimicrobial activities. The intestines of goats could be a potential origin for developing new probiotics applications in animal feed and human health. Hence this study was carried out to determine the antibiotic resistance profiles of LAB and pathogens within the intestines of Nigerian dwarf goats (Capra aegagrus hircus), the antimicrobial activity of LAB against resident MDR pathogens, and subsequent identification of bioactive LAB isolated from goat faeces in Nigeria as potential probiotics in animal feed and human health.
 Method: Selective isolation of the LAB was carried out using de Mann Rogosa Sharpe (MRS) agar while enteric pathogens were isolated on MacConkey agar. Preliminary identification was carried out based on Gram reaction, and morphological, colonial, and biochemical characteristics of each isolate. Antibiotic susceptibility profiles of all isolates were determined using the Kirby-Bauer disc diffusion method. The agar overlay method was used to test the most resistant LAB isolates for antimicrobial activity against enteric pathogens. Selected LAB isolates were identified by 16SrRNA sequencing. 
 Results: The antibiotics susceptibility profile showed that a majority (77%) of LAB isolates and minimal (҇≤10%) of enteric pathogens demonstrated resistance to at least three classes of antibiotics, indicating a pattern of multi-drug resistance. Over half (62%) of these LAB isolates displayed significant antimicrobial activity against at least five of the resident-resistant pathogens, illustrating their potential role in controlling these pathogens. The sequencing results identified the most active LAB isolates, revealing a mix of strains including Pediococcus lolli (46%), Pediococcus pentosaceus (23%), Weissella confusa (8%), Enterococcus faecium (8%), Enterococcus hirae (8%), and Lactobacillus sanfranciscensis (8%).
 Conclusion: The discovery of a diverse range of LAB strains in goat intestines with significant antimicrobial activity against resident enteric pathogens is valuable. This finding suggests the potential use of these bacteria as natural alternatives to traditional antibiotics, especially in the context of growing AMR in animal husbandry.

Inter-plasmid transfer of antibiotic resistance genes accelerates antibiotic resistance in bacterial pathogens.

Antimicrobial resistance is a major threat for public health. Plasmids play a critical role in the spread of antimicrobial resistance via horizontal gene transfer between bacterial species. However, it remains unclear how plasmids originally recruit and assemble various antibiotic resistance genes (ARGs). Here, we track ARG recruitment and assembly in clinically relevant plasmids by combining a systematic analysis of 2420 complete plasmid genomes and experimental validation. Results showed that ARG transfer across plasmids is prevalent, and 87% ARGs were observed to potentially transfer among various plasmids among 8229 plasmid-borne ARGs. Interestingly, recruitment and assembly of ARGs occur mostly among compatible plasmids within the same bacterial cell, with over 88% of ARG transfers occurring between compatible plasmids. Integron and insertion sequences drive the ongoing ARG acquisition by plasmids, especially in which IS26 facilitates 63.1% of ARG transfer events among plasmids. In vitro experiment validated the important role of IS26 involved in transferring gentamicin resistance gene aacC1 between compatible plasmids. Network analysis showed four beta-lactam genes (blaTEM-1, blaNDM-4, blaKPC-2, and blaSHV-1) shuffling among 1029 plasmids and 45 clinical pathogens, suggesting that clinically alarming ARGs transferred accelerate the propagation of antibiotic resistance in clinical pathogens. ARGs in plasmids are also able to transmit across clinical and environmental boundaries, in terms of the high-sequence similarities of plasmid-borne ARGs between clinical and environmental plasmids. This study demonstrated that inter-plasmid ARG transfer is a universal mechanism for plasmid to recruit various ARGs, thus advancing our understanding of the emergence of multidrug-resistant plasmids.

Advanced vaccinomic, immunoinformatic, and molecular modeling strategies for designing Multi- epitope vaccines against the Enterobacter cloacae complex.

The increasing and ongoing issue of antibiotic resistance in bacteria is of huge concern globally, mainly to healthcare facilities. It is now crucial to develop a vaccine for therapeutic and preventive purposes against the bacterial species causing hospital-based infections. Among the many antibiotic- resistant bacterial pathogens, the Enterobacter cloacae complex (ECC) including six species, E. Colcae, E. absuriae, E. kobie, E. hormaechei, E. ludwigii, and E. nimipressuralis, are dangerous to public health and may worsen the situation. Vaccination plays a vital role in the prevention of infections and infectious diseases. This research highlighted the construction and design of a multi-epitope vaccine for the E. cloacae complex by retrieving their complete sequenced proteome. The retrieved proteome was assessed to opt for potential vaccine candidates using immunoinformatic tools. Both B and T-cell epitopes were predicted in order to create both humoral and cellular immunity and further scrutinized for antigenicity, allergenicity, water solubility, and toxicity analysis. The final potential epitopes were subjected to population coverage analysis. Major histocompatibility complex (MHC) class combined, and MHC Class I and II world population coverage was obtained as 99.74%, and 98.55% respectively while a combined 81.81% was covered. A multi-epitope peptide-based vaccine construct consisting of the adjuvant, epitopes, and linkers was subjected to the ProtParam tool to calculate its physiochemical properties. The total amino acids were 236, the molecular weight was 27.64kd, and the vaccine construct was stable with an instability index of 27.01. The Grand Average of Hydropathy (GRAVY) (hydrophilicity) value obtained was -0.659, being more negative and depicting the hydrophilic character. It was non-allergen antigenic with an antigenicity of 0.8913. The vaccine construct was further validated for binding efficacy with immune cell receptors MHC-I, MHC-II, and Toll-like receptor (TLR)-4. The molecular docking results depict that the designed vaccine has good binding potency with immune receptors crucial for antigen presentation and processing. Among the Vaccine-MHC-I, Vaccine-MHC-II, and Vaccine-TLR-4 complexes, the best-docked poses were identified based on their lowest binding energy scores of -886.8, -995.6, and -883.6, respectively. Overall, we observed that the designed vaccine construct can evoke a proper immune response and the construct could help experimental researchers in the formulation of a vaccine against the targeted pathogens.

Etiological structure, clinical and epidemiological characteristics of bloodstream infections caused by resistant microorganisms among COVID-19 patients

Infectious diseases caused by resistant pathogens are a serious public health problem. Generalized forms of resistant infections involving the vascular system in the pathological process are often associated with the irrational use of antimicrobial drugs. The pandemic of a new coronavirus infection (COVID-19) was a significant factor that determined further negative trends in the development of antibiotic resistance. The aim of the study was to investigate the spectrum of microorganisms and analyze clinical and epidemiological data in patients with COVID-19 and bloodstream infections caused by resistant bacterial pathogens in the first 10 months of the pandemic. It has been shown that resistant gram-negative microorganisms are the leading etiological cause of bloodstream infections among hospitalized patients. A. baumannii, as a mono-etiological agent or as part of microbial associations, is the predominant causative pathogen of generalized infections in COVID-19 patients. A high level of comorbidity according to the Charlson index and previous courses of antibiotic therapy can be regarded as potential out-hospital predictors of contamination by resistant pathogens. The severe course of the COVID-19 including of the phenomenon of immunosuppression and the occurrence of sepsis determine the high level of hospital mortality. The addition of generalized infections is an extremely unfavorable factor that worsens the prognosis for recovery.

Biologically active compounds as a means of changing the metabolic activity of pathogenic clinical strains of E. coli and S. Aureus

Microorganisms require nutrients to maintain their physiological functions. Changes in the availability of free amino acids affect the expression of virulence factors, the degree of activity of bacteria, their ability to undergo genetic transformation, and the formation of persistent cells. This study demonstrates that bioactive compounds, such as tryptophan, zinc aspartate, arginine, tatipacin, and taurine, have a modulating effect on the metabolism of microorganisms in vitro. The study found that the metabolic activity of microorganisms increased when exposed to concentrations of bioactive compounds ranging from 0.5–50 µg/ml, particularly in the presence of arginine. Additionally, the presence of BAS in the nutrient medium impacted the growth kinetics of microorganisms. Statistically significant changes were observed compared to the control (without the addition of BAS) after 4 hours of incubation and continued until 36 hours of incubation. The study revealed a significant difference between BAS and control during the 16–24 hour incubation period (p<0.001). The modulation of bacterial activity by BAS can be achieved through various targets and interaction points, such as BAS concentration, the unique cellular structure of the microorganism, its metabolism, and the bacterial pathogen's resistance mechanisms. These findings have broad implications, including the potential for future studies to overcome antibiotic resistance in bacteria.

Drift of antimicrobial resistance of bacterial pathogens of the Moraxella group

The multiple resistance of bacteria to antibiotics leads to a decrease in the effectiveness of treatment methods for bacterial diseases, an increase in morbidity and mortality and, in some cases, to prolonged bacterial transmission. In this regard, the search for new antimicrobial agents and the need to improve veterinary approaches in therapeutic and preventive work with bacterioses is currently a priority task. The study is devoted to the assessment of antibiotic resistance in zoopathogenic moraxella pathogens of infectious bovine keratoconjunctivitis. The article analyzes the drug resistance of topical epizootic strains of Moraxella bovis and M. bovoculi. It was found that since the 1982 study and ending with the own results obtained at the present time, there has been a noticeable increase in the resistance of M. bovis and M. bovoculi to antibiotics. However, a still high level of sensitivity in moraxella is detected for antibiotics of the fluoroquinolone and cephalosporin groups, as well as for ampicillin and benzylpenicillin, the studied bacteria were the most sensitive despite the fact that resistance was recorded for oxacillin and methicillin from the same group.

Bioprospecting of soil-borne microorganisms and chemical dereplication of their anti-microbial constituents with the aid of UPLC-QTOF-MS and molecular networking approach.

Due to the emergence of drug-resistant microorganisms, the search for broad-spectrum antimicrobial compounds has become extremely crucial. Natural sources like plants and soils have been explored for diverse metabolites with antimicrobial properties. This study aimed to identify microorganisms from agricultural soils exhibiting antimicrobial effects against known human pathogens, and to highlight the chemical space of the responsible compounds through the computational metabolomics-based bioprospecting approach. Herein, bacteria were extracted from soil samples and their antimicrobial potential was measured via the agar well diffusion method. Methanolic extracts from the active bacteria were analyzed using the liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) technique, and the subsequent data was further analyzed through molecular networking approach which aided in identification of potential anti-microbial compounds. Furthermore, 16S rRNA gene sequencing enabled identification of the active bacterial isolates, where isolate 1 and 2 were identified as strains of Bacillus pumilus, whilst isolate 3 was found to be Bacillus subtilis. Interestingly, isolate 3 (Bacillus subtilis) displayed wide-ranging antimicrobial activity against the tested human pathogens. Molecular networking revealed the presence of Diketopiperazine compounds such as cyclo (D-Pro-D-Leu), cyclo (L-Tyr-L-Pro), cyclo (L-Pro-D-Phe), and cyclo (L-Pro-L-Val), alongside Surfactin C, Surfactin B, Pumilacidin E, and Isarrin D in the Bacillus strains as the main anti-microbial compounds. The application of the molecular networking approach represents an innovation in the field of bio-guided bioprospection of microorganisms and has proved to be an effective and feasible towards unearthing potent antimicrobial compounds. Additionally, the (computational metabolomics-based) approach accelerates the discovery of bioactive compounds and isolation of strains which offer a promising avenue for discovering new clinical antimicrobials. Finally, soil microbial flora could serve an alternative source of anti-microbial compounds which can assist in the fight against emergence of multi-drug resistance bacterial pathogens.

Bacteriophages Isolation and Efficacy Testing.

Bacteriophages (phages) are viruses that infect bacteria and are the most abundant biological entityon the planet. Phages have gained popularity as an alternative to antibiotics due to their specificity and ability to efficiently lyse antimicrobial resistant bacterial pathogens. Before using phages, they must be isolated from the environment and tested to ensure purity and lytic ability against various hosts. This protocol walks through the entire multi-day procedure of enrichingand processingraw environmental samples (seawater, primary sludge, and soil), testing for lytic activity, selecting and picking potential phage plaques, verifying phage purity, and finally, propagation (liquid and solid) of phages to obtain high-titer crude phage lysates.

Antibiotic Potentiation as a Promising Strategy to Combat Macrolide Resistance in Bacterial Pathogens.

Antibiotics, which hit the market with astounding impact, were once called miracle drugs, as these were considered the ultimate cure for infectious diseases in the mid-20th century. However, today, nearly all bacteria that afflict humankind have become resistant to these wonder drugs once developed to stop them, imperiling the foundation of modern medicine. During the COVID-19 pandemic, there was a surge in macrolide use to treat secondary infections and this persistent use of macrolide antibiotics has provoked the emergence of macrolide resistance. In view of the current dearth of new antibiotics in the pipeline, it is essential to find an alternative way to combat drug resistance. Antibiotic potentiators or adjuvants are non-antibacterial active molecules that, when combined with antibiotics, increase their activity. Thus, potentiating the existing antibiotics is one of the promising approaches to tackle and minimize the impact of antimicrobial resistance (AMR). Several natural and synthetic compounds have demonstrated effectiveness in potentiating macrolide antibiotics against multidrug-resistant (MDR) pathogens. The present review summarizes the different resistance mechanisms adapted by bacteria to resist macrolides and further emphasizes the major macrolide potentiators identified which could serve to revive the antibiotic and can be used for the reversal of macrolide resistance.

A dual mechanism with H2S inhibition and membrane damage of morusin from Morus alba Linn. against MDR-MRSA

It’s urgent to discover new antibiotics along with the increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens. In the present investigation, morusin exhibited rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) by targeting the phospholipid of bacterial inner membrane, increasing membrane rigidity and disrupting bacterial homeostasis together with the membrane permeability, which caused fundamental metabolic disorders. Furthermore, morusin can also accumulate ROS, suppress H2S production, and aggravate oxidative damage in bacteria. Importantly, morusin also inhibited the spread of wounds and reduced the bacterial burden in the mouse model of skin infection caused by MRSA. It’s a chance to meet the challenge of existing antibiotic resistance and avoid the development of bacterial resistance, given the multiple targets of morusin.

Antibiotic Resistance Profiles of Salmonella and Escherichia coli Isolates Obtained from Garden Eggs Sold in Abakaliki Metropolis: Insights into Susceptibility Patterns

This investigation aimed to evaluate the antibiotic susceptibility profiles of Salmonella species and Escherichia coli isolated from 100 garden egg samples obtained from diverse vendors in Abakaliki. Samples were transported to the Department of Applied Microbiology Laboratory, Ebonyi State University, Abakaliki, for analysis. Organisms were isolated and identified using standard microbiological techniques, while their antibiotic susceptibility was assessed through the disc diffusion method. Results indicated a prevalence of 60% for Salmonella species and 80% for E. coli among the analyzed samples. The antibiotic susceptibility testing unveiled alarming resistance patterns: Salmonella species displayed complete resistance (100%) to meropenem, perfloxacin, colistin, aztreonam, neomycin, gentamycin, ciprofloxacin, chloramphenicol, and ofloxacin, with only 16.67% susceptibility to streptomycin. Similarly, E. coli isolates exhibited 87.5% susceptibility solely to ofloxacin and 12.5% to chloramphenicol, while showcasing absolute resistance (100%) to other antibiotics tested. This study underscores the role of garden egg sales and consumption in facilitating the widespread dissemination of multi-drug resistant bacterial pathogens within the region. It emphasizes the urgent need for stringent adherence to hygienic practices among garden egg and other fruit vendors as a crucial preventive measure to curb this escalating threat. Keywords: Garden eggs, Salmonella species, E. coli, antibiotic resistance

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

1706. Risk factors for infections caused by extended spectrum beta lactamase (ESBL) producing and Carbapenem-resistant Enterobacterales (CRE) in pediatric critical care settings: A case control study

Abstract Background Infections due to Gram negative resistant bacterial pathogens are a major concern in intensive care units. The purpose of this study is to determine the risk factors for developing ESBL-producing and CRE infections in pediatric patients in critical care settings (PICU and NICU). Methods A retrospective case control study of infections due to ESBL-producing and CRE during a 5-year period (2016-2021) at Children’s Hospital of Michigan, Detroit. All patients had positive cultures during their PICU/NICU stay. Control cases were matched for age, infection site and year of infection but their cultures grew Enterobacterales that were non-ESBL or carbapenemase producers. Results A total of 58 patients with ESBL/Carbapenemase-producing Enterobacterales (cases) and 59 control patients were included. Majority of organisms were E. coli and Klebsiella species recovered from respiratory tract. There was no difference in both groups in regards to age, gender, race or length of hospital stay (p >0.3). There was no difference in prior hospital admission, PICU or NICU stay during the previous 6 months, indwelling devices, comorbid conditions, or surgery in the last 6 months (p >0.3). However, the presence of gastrostomy tube was more frequent in the cases group (29.3%) than the control group (15.3%) (p=0.078). Risk factors by univariate analysis included history of antibiotic use in last 6 months (93% in cases vs 73% in controls; p=0.006), cephalosporins use > 14 days (67% vs 31.2%; p=0.006),Trimethoprim/Sulfamethoxazole treatment duration > 14 days (11.1% vs 0%; p=0.012), carbapenem treatment duration > 14 days (14% vs 1.9%; p=0.027), and vancomycin use > 14 days (43.6% vs 21.6%; p=0.053). However, multivariate logistic regression analysis showed that antibiotic usage in the last 6 months was the single best predictor for cases with odds ratio of 5.02-fold (95% CI 1.56-16.13) (p=0.007). Conclusion Prior broad spectrum antibiotic usage was significantly associated with acquisition of ESBL and carbapenemase producing Enterobacterales. The study further underscores the need for optimizing antimicrobial stewardship practices to limit unnecessary and prolonged use of antibiotics to prevent the emergence of resistant pathogens. Disclosures All Authors: No reported disclosures

Interpretable machine learning-based decision support for prediction of antibiotic resistance for complicated urinary tract infections

Urinary tract infections are one of the most common bacterial infections worldwide; however, increasing antimicrobial resistance in bacterial pathogens is making it challenging for clinicians to correctly prescribe patients appropriate antibiotics. In this study, we present four interpretable machine learning-based decision support algorithms for predicting antimicrobial resistance. Using electronic health record data from a large cohort of patients diagnosed with potentially complicated UTIs, we demonstrate high predictability of antibiotic resistance across four antibiotics – nitrofurantoin, co-trimoxazole, ciprofloxacin, and levofloxacin. We additionally demonstrate the generalizability of our methods on a separate cohort of patients with uncomplicated UTIs, demonstrating that machine learning-driven approaches can help alleviate the potential of administering non-susceptible treatments, facilitate rapid effective clinical interventions, and enable personalized treatment suggestions. Additionally, these techniques present the benefit of providing model interpretability, explaining the basis for generated predictions.

Quercetin induces pathogen resistance through the increase of salicylic acid biosynthesis in Arabidopsis

ABSTRACT Quercetin is a flavonol belonging to the flavonoid group of polyphenols. Quercetin is reported to have a variety of biological functions, including antioxidant, pigment, auxin transport inhibitor and root nodulation factor. Additionally, quercetin is known to be involved in bacterial pathogen resistance in Arabidopsis through the transcriptional increase of pathogenesis-related (PR) genes. However, the molecular mechanisms underlying how quercetin promotes pathogen resistance remain elusive. In this study, we showed that the transcriptional increases of PR genes were achieved by the monomerization and nuclear translocation of nonexpressor of pathogenesis-related proteins 1 (NPR1). Interestingly, salicylic acid (SA) was approximately 2-fold accumulated by the treatment with quercetin. Furthermore, we showed that the increase of SA biosynthesis by quercetin was induced by the transcriptional increases of typical SA biosynthesis-related genes. In conclusion, this study strongly suggests that quercetin induces bacterial pathogen resistance through the increase of SA biosynthesis in Arabidopsis.