scholarly journals A Microbiome-Based Solution to Address Alarming Levels of Drug-Resistant Bacteria in the Newborn Infant Gut

2020 ◽  
Vol 41 (S1) ◽  
pp. s439-s439
Author(s):  
Giorgio Casaburi ◽  
Rebbeca Duar ◽  
Bethany Henrick ◽  
Steven Frese
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Bacterial Species ◽  
The United States ◽  
Resistant Bacteria ◽  
Delivery Mode ◽  
Term Infants ◽  
Shotgun Metagenomics ◽  
Single Strain ◽  
Breastfed Infants

Background: Recent studies have focused on the early infant gut microbiome, indicating that antibiotic resistance genes (ARGs) can be acquired in early life and may have long-term sequelae. Limiting the spread of antimicrobial resistance without triggering the development of additional resistance mechanisms would be of immense clinical value. Here, we present 2 analyses that highlight the abundance of ARGs in preterm and term infants and a proof of concept for modulating the microbiome to promote early stabilization and reduction in ARGs in term infants. Methods: Large-scale metagenomic analysis was performed on 2,141 microbiome samples (90% from pre-term infants) from 10 countries; most were from the United States (87%) and were obtained from the Comprehensive Antibiotic Resistance Database (CARD). We assessed the abundance and specific types of ARGs present. In the second study, healthy, breastfed infants were fed B. infantis EVC001 for 3 weeks starting at postnatal day 7. Stool samples were collected at day 21 and were processed utilizing shotgun metagenomics. Selected antimicrobial-resistant bacterial species were isolated, sequenced, and tested for minimal inhibitory concentrations to clinically relevant antibiotics. Results: In the first study, globally, 417 distinct ARGs were identified. The most abundant gene among all samples was annotated as msrE, a plasmid gene known to confer resistance to macrolide-lincosamide-streptogramin B (MLSB) antibiotics. The remaining most-abundant ARGs were efflux-pump genes associated with multidrug resistance. No significant association in antimicrobial resistance was found when considering delivery mode or antibiotic treatment in the first month of life. In the second study, the EVC001-fed group showed a significant decrease (90%) in ARGs compared to controls (P < .0001). ARGs that differed significantly between groups were predicted to confer resistance to β-lactams, fluoroquinolones, or multiple drug classes. Minimal inhibitory concentration assays confirmed resistance phenotypes among isolates Notably, we found resistance to extended-spectrum β-lactamases among healthy, vaginally delivered breastfed infants who had never been exposed to antibiotics. Conclusions: In this study, we show that the term and preterm infant microbiome contains alarming levels of ARGs associated with clinically relevant antibiotics harbored by bacteria commonly responsible for nosocomial infections. Colonization of the breastfed infant gut by a single strain of B. longum subsp infantis had profound impacts on the fecal metagenome, including reduction in ARGs and reduction of potential pathogens. These findings highlight the importance of developing novel approaches to limit the spread of ARGs among clinically relevant bacteria and the relevance of an additional approach in the effort to solve AR globally.Funding: Evolve BioSystems provided Funding: for this study.Disclosures: Giorgio Casaburi reports salary from Evolve BioSystems.

scholarly journals Transmission of Antibiotic Resistant Bacteria and Genes: Unveiling the Jigsaw Pieces of a One Health Problem

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 497
Author(s):  
Carla Novais ◽  
Ana R. Freitas
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Global Health ◽  
Large Scale ◽  
One Health ◽  
Metal Tolerance ◽  
Bacterial Species ◽  
Common Species ◽  
World Health ◽  
Resistant Bacteria

Antimicrobial Resistance is one of the major Global Health challenges of the twenty-first century, and one of the World Health Organization’s (WHO) top ten global health threats. The evolution of antibiotic resistance among bacterial pathogens requires urgent concerted global efforts under a One Health approach integrating human, animal, and environmental surveillance data. This is crucial to develop efficient control strategies and counteract the spread of multidrug-resistant pathogens. The studies in this Special Issue have evidenced the hidden role of less common species, unusual clones or unexplored niches in the dissemination of antimicrobial resistance between different hosts. They reinforce the need for large-scale surveillance studies tracing and tracking both antibiotic resistance and metal tolerance in different bacterial species.

scholarly journals The Role of Aquatic Ecosystems (River Tua, Portugal) as Reservoirs of Multidrug-Resistant Aeromonas spp.

Water ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 698
Author(s):  
Sónia Gomes ◽  
Conceição Fernandes ◽  
Sandra Monteiro ◽  
Edna Cabecinha ◽  
Amílcar Teixeira ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Nalidixic Acid ◽  
Water Samples ◽  
Aquatic Ecosystems ◽  
Anthropogenic Activities ◽  
Aquatic Organisms ◽  
Resistant Bacteria ◽  
Anthropogenic Pressures ◽  
Resistance Rates

The inappropriate use of antibiotics, one of the causes of the high incidence of antimicrobial-resistant bacteria isolated from aquatic ecosystems, represents a risk for aquatic organisms and the welfare of humans. This study aimed to determine the antimicrobial resistance rates among riverine Aeromonas spp., taken as representative of the autochthonous microbiota, to evaluate the level of antibacterial resistance in the Tua River (Douro basin). The prevalence and degree of antibiotic resistance was examined using motile aeromonads as a potential indicator of antimicrobial susceptibility for the aquatic environment. Water samples were collected from the middle sector of the river, which is most impacted area by several anthropogenic pressures. Water samples were plated on an Aeromonas-selective agar, with and without antibiotics. The activity of 19 antibiotics was studied against 30 isolates of Aeromonas spp. using the standard agar dilution susceptibility test. Antibiotic resistance rates were fosfomycin (FOS) 83.33%, nalidixic acid (NA) 60%, cefotaxime (CTX) 40%, gentamicin (CN) 26.67%, tobramycin (TOB) 26.67%, cotrimoxazole (SXT) 26.67%, chloramphenicol (C) 16.67%, and tetracycline (TE) 13.33%. Some of the nalidixic acid-resistant strains were susceptible to fluoroquinolones. Multiple resistance was also observed (83.33%). The environmental ubiquity, the natural susceptibility to antimicrobials and the zoonotic potential of Aeromonas spp. make them optimal candidates for studying antimicrobial resistance (AMR) in aquatic ecosystems. Aquatic environments may provide an ideal setting for the acquisition and dissemination of antibiotic resistance because anthropogenic activities frequently impact them. The potential risk of multi- and pan-resistant bacteria transmission between animals and humans should be considered in a “One Health—One World” concept.

scholarly journals Patient-Specific Predictive Antibiogram in Decision Support for Empiric Antibiotic Treatment

2020 ◽  
Vol 41 (S1) ◽  
pp. s521-s522
Author(s):  
Debarka Sengupta ◽  
Vaibhav Singh ◽  
Seema Singh ◽  
Dinesh Tewari ◽  
Mudit Kapoor ◽  
...  
Keyword(s):  
Machine Learning ◽  
Antimicrobial Resistance ◽  
Model Building ◽  
Medical Center ◽  
Bacterial Species ◽  
Model Performance ◽  
The United States ◽  
Patient Specific ◽  
Gradient Boosting ◽  
Comparative Performance

Background: The rising trend of antibiotic resistance imposes a heavy burden on healthcare both clinically and economically (US$55 billion), with 23,000 estimated annual deaths in the United States as well as increased length of stay and morbidity. Machine-learning–based methods have, of late, been used for leveraging patient’s clinical history and demographic information to predict antimicrobial resistance. We developed a machine-learning model ensemble that maximizes the accuracy of such a drug-sensitivity versus resistivity classification system compared to the existing best-practice methods. Methods: We first performed a comprehensive analysis of the association between infecting bacterial species and patient factors, including patient demographics, comorbidities, and certain healthcare-specific features. We leveraged the predictable nature of these complex associations to infer patient-specific antibiotic sensitivities. Various base-learners, including k-NN (k-nearest neighbors) and gradient boosting machine (GBM), were used to train an ensemble model for confident prediction of antimicrobial susceptibilities. Base learner selection and model performance evaluation was performed carefully using a variety of standard metrics, namely accuracy, precision, recall, F1 score, and Cohen &kappa;. Results: For validating the performance on MIMIC-III database harboring deidentified clinical data of 53,423 distinct patient admissions between 2001 and 2012, in the intensive care units (ICUs) of the Beth Israel Deaconess Medical Center in Boston, Massachusetts. From ~11,000 positive cultures, we used 4 major specimen types namely urine, sputum, blood, and pus swab for evaluation of the model performance. Figure 1 shows the receiver operating characteristic (ROC) curves obtained for bloodstream infection cases upon model building and prediction on 70:30 split of the data. We received area under the curve (AUC) values of 0.88, 0.92, 0.92, and 0.94 for urine, sputum, blood, and pus swab samples, respectively. Figure 2 shows the comparative performance of our proposed method as well as some off-the-shelf classification algorithms. Conclusions: Highly accurate, patient-specific predictive antibiogram (PSPA) data can aid clinicians significantly in antibiotic recommendation in ICU, thereby accelerating patient recovery and curbing antimicrobial resistance.Funding: This study was supported by Circle of Life Healthcare Pvt. Ltd.Disclosures: None

scholarly journals Antimicrobial Resistance among Neonates with Bacterial Sepsis and Their Clinical Outcomes in a Tertiary Hospital in Kathmandu Valley, Nepal

2021 ◽  
Vol 6 (2) ◽  
pp. 56
Author(s):  
Bijendra Raj Raghubanshi ◽  
Karuna D. Sagili ◽  
Wai Wai Han ◽  
Henish Shakya ◽  
Priyanka Shrestha ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Neonatal Sepsis ◽  
Bacterial Culture ◽  
Bacterial Species ◽  
Antibiotic Sensitivity ◽  
College Teaching ◽  
Hospital Treatment ◽  
Resistant Bacteria ◽  
Coagulase Negative Staphylococcus ◽  
Cross Sectional

Globally, antibiotic resistance in bacteria isolated from neonatal sepsis is increasing. In this cross-sectional study conducted at a medical college teaching hospital in Nepal, we assessed the antibiotic resistance levels in bacteria cultured from neonates with sepsis and their in-hospital treatment outcomes. We extracted data of neonates with sepsis admitted for in-patient care from June 2018 to December 2019 by reviewing hospital records of the neonatal intensive care unit and microbiology department. A total of 308 neonates with sepsis were admitted of which, blood bacterial culture antibiotic sensitivity reports were available for 298 neonates. Twenty neonates (7%) had bacteriologic culture-confirmed neonatal sepsis. The most common bacterial species isolated were Staphylococcus aureus (8), followed by coagulase-negative Staphylococcus (5). Most of these bacteria were resistant to at least one first-line antibiotic used to manage neonatal sepsis. Overall, there were 7 (2%) deaths among the 308 neonates (none of them from the bacterial culture-positive group), and 53 (17%) neonates had left the hospital against medical advice (LAMA). Improving hospital procedures to isolate bacteria in neonates with sepsis, undertaking measures to prevent the spread of antibiotic-resistant bacteria, and addressing LAMA’s reasons are urgently needed.

scholarly journals The Infant Gut Resistome is Associated with E. coli and Early-life Exposures

2020 ◽  
Author(s):  
Rebecca M. Lebeaux ◽  
Modupe O. Coker ◽  
Erika F. Dade ◽  
Thomas J. Palys ◽  
Hilary G. Morrison ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Relative Risk ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
Early Life ◽  
The United States ◽  
Delivery Mode ◽  
Metagenomic Sequencing ◽  
E Coli ◽  
Early Life Exposures

Abstract Background: Antibiotic resistance is an increasing threat to human health. The human gut microbiome harbors a collection of bacterial antimicrobial resistance genes (ARGs) known as the resistome. The factors associated with establishment of the resistome in early life are not well understood and clarifying these factors would inform strategies to decrease antibiotic resistance. We investigated the early-life exposures and taxonomic signatures associated with resistome development over the first year of life in a large, prospective cohort in the United States. Shotgun metagenomic sequencing was used to profile both microbial composition and ARGs in stool samples collected at 6 weeks and 1 year of age from infants enrolled in the New Hampshire Birth Cohort Study. Negative binomial regression and statistical modeling was used to examine infant factors such as sex, delivery mode, feeding method, gestational age, antibiotic exposure, and infant gut microbiome composition in relation to the diversity and relative abundance of ARGs.Results: Metagenomic sequencing was performed on paired samples from 195 full term (at least 37 weeks’ gestation) and 15 late preterm (33-36 weeks’ gestation) infants. 6-week samples compared to 1-year samples had 4.37 times (95% CI: 3.54-5.39) the rate of harboring ARGs. The majority of ARGs that were at a greater relative abundance at 6 weeks (chi-squared p < 0.01) worked through the mechanism of antibiotic efflux (i.e., by pumping antibiotics out of the cell). The overall relative abundance of the resistome was strongly correlated with Proteobacteria (Spearman correlation = 78.9%) and specifically E. coli (62.2%) relative abundance in the gut microbiome. Among infant characteristics, delivery mode was most strongly associated with the diversity and relative abundance of ARGs. Infants born via cesarean delivery had a higher risk of harboring unique ARGs [relative risk = 1.12 (95% CI: 0.97 – 1.29)] as well as a having an increased risk for overall ARG relative abundance [relative risk = 1.43 (95% CI: 1.12 – 1.84)] at 1 year compared to infants born vaginally. Additionally, 6 specific ARGs were at a greater relative abundance in infants delivered by cesarean section compared to vaginally delivered infants across both time points. Conclusions: Our findings suggest that the developing infant gut resistome may be alterable by early-life exposures. Establishing the extent to which infant characteristics and early-life exposures impact the resistome can ultimately lead to interventions that decrease the transmission of ARGs and thus the possibility of antibiotic resistant life threatening infections.

Comparing antibiotic resistance in commensal and pathogenic bacteria isolated from wild-caught South Carolina shrimps vs. farm-raised imported shrimps

2007 ◽  
Vol 53 (7) ◽  
pp. 919-924 ◽  
Author(s):  
Kavitha Boinapally ◽  
Xiuping Jiang
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
South Carolina ◽  
Antimicrobial Resistance ◽  
Pathogenic Bacteria ◽  
Vibrio Vulnificus ◽  
Resistant Bacteria ◽  
Microbiological Analysis ◽  
Salmonella Spp ◽  
Plate Counts

The objective of this study was to assess and differentiate wild-caught South Carolina (SC) shrimps from imported shrimps on the basis of microbiological analysis. Seven wild-caught SC shrimp and 13 farm-raised imported shrimp samples were analyzed. Total plate counts from wild-caught shrimp samples ranged from 4.3 to 7.0 log10 CFU/g, whereas counts from imported shrimp samples ranged from 3.2 to 5.7 log10 CFU/g. There was no difference (P > 0.05) between total bacterial counts of wild-caught SC shrimp and farm-raised imported shrimp. However, the percentages of bacteria with reduced susceptibility towards ceftriaxone and tetracycline were higher (P < 0.05) for farm-raised shrimp than for wild-caught samples. Salmonella spp. detected only in one farm-raised sample was resistant to ampicillin, ceftriaxone, gentamicin, streptomycin, and trimethoprim. Vibrio vulnificus was detected in both wild-caught and farm-raised shrimp samples; however, only the isolate from farm-raised shrimp was resistant to nalidixic acid and trimethoprim. Escherichia coli detected in one wild-caught sample was resistant to ampicillin. Both Listeria spp. and Salmonella spp. were absent with wild-caught SC samples. Therefore, the presence of more ceftriaxone- and tetracycline-resistant bacteria and the observed antimicrobial resistance phenotypes of isolates from the imported shrimp may reflect the possible use of antibiotics in raising shrimp in those countries.

scholarly journals The Inactivation of Enzymes Belonging to the Central Carbon Metabolism Is a Novel Mechanism of Developing Antibiotic Resistance

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Teresa Gil-Gil ◽  
Fernando Corona ◽  
José Luis Martínez ◽  
Alejandra Bernardini
Keyword(s):  
Antibiotic Resistance ◽  
Stenotrophomonas Maltophilia ◽  
Bacterial Species ◽  
Bacterial Metabolism ◽  
Resistant Bacteria ◽  
Uridine Diphosphate ◽  
Biosynthesis Pathway ◽  
Content Type ◽  
Peptidoglycan Biosynthesis ◽  
Central Carbon

ABSTRACT Fosfomycin is a bactericidal antibiotic, analogous to phosphoenolpyruvate, that exerts its activity by inhibiting the activity of MurA. This enzyme catalyzes the first step of peptidoglycan biosynthesis, the transfer of enolpyruvate from phosphoenolpyruvate to uridine-diphosphate-N-acetylglucosamine. Fosfomycin is increasingly being used, mainly for treating infections caused by Gram-negative multidrug-resistant bacteria. The mechanisms of mutational resistance to fosfomycin in Stenotrophomonas maltophilia, an opportunistic pathogen characterized by its low susceptibility to commonly used antibiotics, were studied in the current work. None of the mechanisms reported so far for other organisms, which include the production of fosfomycin-inactivating enzymes, target modification, induction of an alternative peptidoglycan biosynthesis pathway, and the impaired entry of the antibiotic, are involved in the acquisition of such resistance by this bacterial species. Instead, the unique cause of resistance in the mutants studied is the mutational inactivation of different enzymes belonging to the Embden-Meyerhof-Parnas central metabolism pathway. The amount of intracellular fosfomycin accumulation did not change in any of these mutants, showing that neither inactivation nor transport of the antibiotic is involved. Transcriptomic analysis also showed that the mutants did not present changes in the expression level of putative alternative peptidoglycan biosynthesis pathway genes or any related enzyme. Finally, the mutants did not present an increased phosphoenolpyruvate concentration that might compete with fosfomycin for its binding to MurA. On the basis of these results, we describe a completely novel mechanism of antibiotic resistance based on mutations of genes encoding metabolic enzymes. IMPORTANCE Antibiotic resistance has been largely considered a specific bacterial response to an antibiotic challenge. Indeed, its study has been mainly concentrated on mechanisms that affect the antibiotics (mutations in transporters, efflux pumps, and antibiotic-modifying enzymes, or their regulators) or their targets (i.e., target mutations, protection, or bypass). Usually, antibiotic resistance-associated metabolic changes were considered a consequence (fitness costs) and not a cause of antibiotic resistance. Herein, we show that alterations in the central carbon bacterial metabolism can also be the cause of antibiotic resistance. In the study presented here, Stenotrophomonas maltophilia acquires fosfomycin resistance through the inactivation of glycolytic enzymes belonging to the Embden-Meyerhof-Parnas pathway. Besides resistance to fosfomycin, this inactivation also impairs the bacterial gluconeogenic pathway. Together with previous work showing that antibiotic resistance can be under metabolic control, our results provide evidence that antibiotic resistance is intertwined with the bacterial metabolism.

scholarly journals Prevalence and Antimicrobial Susceptibility of Indicator Organisms Escherichia coli and Enterococcus spp. Isolated from U.S. Animal Food, 2005–2011

2020 ◽  
Vol 8 (7) ◽  
pp. 1048 ◽  
Author(s):  
Beilei Ge ◽  
Kelly J. Domesle ◽  
Stuart A. Gaines ◽  
Claudia Lam ◽  
Sonya M. Bodeis Jones ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Animal Feed ◽  
The United States ◽  
Resistant Bacteria ◽  
Indicator Organisms ◽  
Pet Food ◽  
Animal Food ◽  
E Coli ◽  
Enterococcus Spp

The role animal food plays in the introduction of antimicrobial-resistant bacteria into the human food chain is not well understood. We conducted an analysis of 1025 samples (647 pet food and 378 animal feed) collected across the United States during 2005–2011 for two indicator organisms (Escherichia coli and Enterococcus spp.). The overall prevalence ranged from 12.5% for E. coli to 45.2% for Enterococcus spp., and 11.2% of samples harbored both organisms. Regardless of bacterial genus, animal feed had significantly higher prevalence than pet food (p < 0.001). A general downward trend in prevalence was observed from 2005 to 2009 followed by an upward trend thereafter. Among E. coli isolates (n = 241), resistance was highest to tetracycline (11.2%) and below 5% for fourteen other antimicrobials. Among Enterococcus spp. isolates (n = 1074), Enterococcus faecium (95.1%) was the predominant species. Resistance was most common to tetracycline (30.1%) and ciprofloxacin (10.7%), but below 10% for thirteen other antimicrobials. Multidrug-resistant organisms were observed among both E. coli and Enterococcus spp. isolates at 3.3%. Compared to National Antimicrobial Resistance Monitoring System (NARMS) 2011 retail meat and animal data, the overall resistance for both organisms was much lower in animal food. These findings help establish a historic baseline for the prevalence and antimicrobial resistance among U.S. animal food products and future efforts may be needed to monitor changes over time.

scholarly journals Anthropogenic Activities and the Problem of Antibiotic Resistance in Latin America: A Water Issue

Water ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 2693
Author(s):  
Delfina C. Domínguez ◽  
Luz María Chacón ◽  
D’Janique Wallace
Keyword(s):  
Antibiotic Resistance ◽  
Latin America ◽  
Antimicrobial Resistance ◽  
Latin American ◽  
Anthropogenic Activities ◽  
Antibiotic Use ◽  
Modern Medicine ◽  
Resistant Bacteria ◽  
Beta Lactam ◽  
Water Ecosystems

Antibiotics revolutionized modern medicine and have been an excellent tool to fight infections. However, their overuse and misuse in different human activities such as health care, food production and agriculture has resulted in a global antimicrobial resistance crisis. Some regions such as Latin America present a more complex scenario because of the lack of resources, systematic studies and legislation to control the use of antimicrobials, thus increasing the spread of antibiotic resistance. This review aims to summarize the state of environmental antibiotic resistance in Latin America, focusing on water resources. Three databases were searched to identify publications on antimicrobial resistance and anthropogenic activities in relation to natural and artificial water ecosystems. We found that antibiotic resistant bacteria, mainly against beta lactam antibiotics, have been reported in several Latin American countries, and that resistant bacteria as well as resistant genes can be isolated from a wide variety of aquatic environments, including drinking, surface, irrigation, sea and wastewater. It is urgent to establish policies and regulations for antibiotic use to prevent the increase of multi-drug resistant microorganisms in the environment.

scholarly journals Hospital use of antibiotics as the main driver of infections with antibiotic-resistant bacteria – a reanalysis of recent data from the European Union

2019 ◽  
Author(s):  
Matthias M. Fischer ◽  
Matthias Bild
Keyword(s):  
European Union ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Antibiotic Use ◽  
Resistant Bacteria ◽  
Individual Member ◽  
The European Union ◽  
Hospital Sector ◽  
Main Driver ◽  
Resistance Rates

AbstractAntimicrobial resistance in bacteria causes significant morbidity worldwide. The development and acquisition of resistance to antibiotics is believed to primarily develop under the selective pressure of widespread antibiotic use in humans, however antimicrobial usage in livestock has been proposed as additional, if not principal, driver of antibiotic resistance. In this work, we correlate recent data from the European Union on antibiotic resistance rates with data on antibiotic usage in the primary care and hospital sector and data on veterinary antimicrobial consumption across the individual member states. We quantify the strength of these different potential drivers of antimicrobial resistance in order to compare their biological importance. We found that the correlation between antibiotic use in the hospital sector and antibiotic resistance rates is significantly higher than the correlation between resistance rates and any of the other two predictors. This suggests increased antibiotic use in hospitals as the main driver of the development of antibiotic resistances and necessitates further research on and a re-evaluation of the risks associated with antibiotic use in human and veterinary medicine.

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