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.

scholarly journals 180. Alterations to the Gut Microbiomes and Acquisition of Bacteria Resistance Elements among US International Travelers

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S110-S110
Author(s):  
Sushmita Sridhar ◽  
Colin Worby ◽  
Ryan Bronson ◽  
Sarah Turbett ◽  
Jason Harris ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
South America ◽  
South Asia ◽  
Relative Abundance ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
International Travel ◽  
South East Asia ◽  
E Coli ◽  
Geographic Regions

Abstract Background This study investigated the impact of international travel on the acquisition and carriage of antimicrobial resistance (AMR). We prospectively assessed U.S. international travelers for the acquisition of resistant Enterobacterales species and evaluated changes in travelers’ gut microbiomes. Methods Metagenomic sequencing was performed on DNA extracted from pre- and post-travel stool samples of 273 U.S. international travelers. We used Kraken2 to assess microbial gut composition and analyzed antibiotic resistance gene (ARG) content using the Resistance Gene Identifier (RGI) and ResFinder, and read mapping to ARG databases. We assessed the change in gut profile and resistome associated with (i) all international travel; (ii) travel to specific geographic regions; and (iii) traveler’s diarrhea. Results International travel resulted in a perturbation of the gut microbiome, which was greater in travelers receiving treatment for diarrhea during travel (p = 4E-5). There was an overall loss in microbial diversity following travel, regardless of health outcome (p = 0.011); this was most consistently observed in travelers to South East Asia (SEA) (loss of gut diversity in 81% of SEA travelers). 78% of all travelers had a higher relative abundance of E. coli after travel, including 85% of travelers who acquired AMR bacteria during travel. Travel to South Asia was also associated with a significantly greater increase of E. coli relative to other destinations (p = 0.04). Additionally, the relative abundance of Pasteurellales was higher in the pre-travel samples of those who subsequently acquired AMR bacteria (FDR = 0.08). Furthermore, there was a significant increase in ARG content among the post-travel samples, with regional differences in the magnitude of acquisition (Figure 1). 72% of all travelers had a greater resistance burden post-travel. SEA was associated with the greatest increase in resistome diversity, while South America was associated with the greatest increase in overall ARG content. Resistance genes present in the gut microbiome. Genes mapping to the Comprehensive Antibiotic Resistance Database were measured pre- (x-axis) and post-travel (y-axis) to assess the acquisition of resistance genes in association with travel, distinguished by geographic region. Colors indicate geographic regions visited by travelers: South America (red), South East Asia (blue), South Asia (green), Eastern Africa (purple), Southern Africa (orange), Other (grey). Conclusion International travel is associated with a perturbation in the gut microbial community, with the acquisition of AMR bacteria and genes, and an increase in the relative abundance of E. coli. These perturbations following travel may be important factors in the global spread of AMR. Disclosures All Authors: No reported disclosures

scholarly journals Delivery mode impacts newborn gut colonization efficiency

2020 ◽  
Author(s):  
Caroline Mitchell ◽  
Larson Hogstrom ◽  
Allison Bryant ◽  
Agnes Bergerat ◽  
Avital Cher ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Dominant Factor ◽  
Delivery Mode ◽  
Metagenomic Sequencing ◽  
Vaginal Microbiome ◽  
Abdominal Incision ◽  
Birth Canal ◽  
Microbiome Composition ◽  
Gut Colonization ◽  
Infant Gut Microbiome

AbstractDelivery mode is the variable with the greatest influence on the infant gut microbiome composition in the first few months of life. Children born by Cesarean section (C-section) lack species from the Bacteroides genus in their gut microbial community, and this difference can be detectable until 6-18 months of age. One hypothesis is that these differences stem from lack of exposure to the maternal vaginal microbiome, as children born by C-section do not pass through the birth canal; however, Bacteroides species are not common members of the vaginal microbiome, thus this explanation seems inadequate. Here, we set out to re-evaluate this hypothesis by collecting rectal and vaginal samples before delivery from 73 mothers with paired stool from their infants in the first two weeks of life. We compared microbial profiles of infants born by planned, pre-labor C-section to those born by emergent, post-labor surgery (where the child was in the birth canal, but eventually delivered through an abdominal incision), and found no significant differences in the microbiome between these two groups. Both groups showed the characteristic signature lack of Bacteroides species, despite their difference in exposure to the birth canal. Surprisingly, this signature was only evident in samples from week two of life, but not in the first week. Children born by C-section often had high abundance of Bacteroides in their first few days of life, but these were not stable colonizers of the infant gut, as they were not detectable by week two. Finally, we used metagenomic sequencing to compare microbial strains in maternal vaginal and rectal samples and samples from their infants; we found evidence for mother-to-child transmission of rectal rather than vaginal strains. These results challenge birth canal exposure as the dominant factor in infant gut microbiome establishment and implicate colonization efficiency rather than exposure as a dictating factor of the newborn gut microbiome composition.

scholarly journals Weaning age and its effect on the development of the swine gut microbiome and resistome

2021 ◽  
Author(s):  
Devin B Holman ◽  
Katherine E Gzyl ◽  
Kathy T Mou ◽  
Heather K Allen
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
Rrna Gene ◽  
Metagenomic Sequencing ◽  
Carbohydrate Active Enzymes ◽  
Fecal Microbiome ◽  
Shotgun Metagenomic Sequencing ◽  
Swine Operations ◽  
Weaning Age

Piglets are often weaned between 19 and 22 d of age in North America although in some swine operations this may occur at 14 d or less. Piglets are abruptly separated from their sow at weaning and are quickly transitioned from sow's milk to a plant-based diet. The effect of weaning age on the long-term development of the pig gut microbiome is largely unknown. In this study, pigs were weaned at either 14, 21, or 28 d of age and fecal samples collected 21 times from d 4 (neonatal) through to marketing at d 140. The fecal microbiome was characterized using 16S rRNA gene and shotgun metagenomic sequencing. The fecal microbiome of all piglets shifted significantly three to seven days post-weaning with an increase in microbial diversity. Several Prevotella spp. increased in relative abundance immediately after weaning as did butyrate-producing species such as Butyricicoccus porcorum, Faecalibacterium prausnitzii, and Megasphaera elsdenii. Within 7 days of weaning, the gut microbiome of pigs weaned at 21 and 28 days of age resembled that of pigs weaned at 14 d. Resistance genes to most antimicrobial classes decreased in relative abundance post-weaning with the exception of those conferring resistance to tetracyclines and macrolides-lincosamides-streptogramin B. The relative abundance of microbial carbohydrate-active enzymes (CAZymes) changed significantly in the post-weaning period with an enrichment of CAZymes involved in degradation of plant-derived polysaccharides. These results demonstrate that pigs tend to have a more similar microbiome as they age and that weaning age has only a temporary effect on the gut microbiome.

scholarly journals Alterations in gut microbiome composition and function in irritable bowel syndrome and increased probiotic abundance with daily supplementation

2021 ◽  
Author(s):  
Joann Phan ◽  
Divya Nair ◽  
Suneer Jain ◽  
Thibaut Montagne ◽  
Demi Valeria Flores ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiome ◽  
The United States ◽  
Supporting Evidence ◽  
Metagenomic Sequencing ◽  
Healthy Controls ◽  
Microbiome Composition ◽  
Significant Difference ◽  
Stool Samples ◽  
Irritable Bowel

AbstractBackgroundIrritable bowel syndrome (IBS) is characterized by abdominal discomfort and irregular bowel movements and stool consistency. Because there are different symptoms associated with IBS, it is difficult to diagnose the role of the microbiome in IBS.ObjectiveHere, we present a study that includes metagenomic sequencing of stool samples from subjects with the predominant subtypes of IBS and a healthy cohort. We collected longitudinal samples from individuals with IBS who took daily made-to-order precision probiotic and prebiotic supplementation throughout the study.Materials and MethodsThis study includes a population of 489 individuals with IBS and 122 healthy controls. All stool samples were subjected to shotgun metagenomic sequencing. Precision probiotics and prebiotics were formulated for all subjects with longitudinal timepoints.ResultsThere was significant variation explained in the microbiome between the healthy and IBS cohorts. Individuals with IBS had a lower gut microbiome diversity and reduced anti-inflammatory microbes compared to the healthy controls. Eubacterium rectale and Faecalibacterium prausnitzii were associated with healthy microbiomes while Shigella species were associated with IBS. Pathway analysis indicated a functional imbalance of short chain fatty acids, vitamins, and a microbial component of Gram-negative bacteria in IBS compared to healthy controls. In the longitudinal dataset, there was a significant difference in microbiome composition between timepoints 1 and 3. There was also a significant increase in the overall microbiome score and relative abundances of probiotic species used to target the symptoms associated with IBS.ConclusionsWe identified microbes and pathways that differentiate healthy and IBS microbiomes. In response to precision probiotic supplementation, we identified a significant improvement in the overall microbiome score in individuals with IBS. These results suggest an important role for probiotics in managing IBS symptoms and modulation of the microbiome as a potential management strategy.ImportanceAn estimated 35 million people in the United States and 11.5% of the population globally are affected by IBS. Immunity, genetics, environment, diet, small intestinal bacterial overgrowth (SIBO), and the gut microbiome are all factors that contribute to the onset or triggers of IBS. With strong supporting evidence that the gut microbiome may influence symptoms associated with IBS, elucidating the important microbes that contribute to the symptoms and severity is important to make decisions for targeted treatment. As probiotics have become more common in treating IBS symptoms, identifying effective probiotics may help inform future studies and treatment.

scholarly journals Antibiotic Resistance Genes in Lemur Gut and Soil Microbiota Along a Gradient of Anthropogenic Disturbance

2021 ◽  
Vol 9 ◽  
Author(s):  
Sally L. Bornbusch ◽  
Christine M. Drea
Keyword(s):  
Antibiotic Resistance ◽  
Antibiotic Treatment ◽  
Resistance Genes ◽  
Anthropogenic Disturbance ◽  
Antibiotic Resistance Genes ◽  
Single Species ◽  
The United States ◽  
Metagenomic Sequencing ◽  
Natural Habitats ◽  
Human Contact

The overuse of man-made antibiotics has facilitated the global propagation of antibiotic resistance genes in animals, across natural and anthropogenically disturbed environments. Although antibiotic treatment is the most well-studied route by which resistance genes can develop and spread within host-associated microbiota, resistomes also can be acquired or enriched via more indirect routes, such as via transmission between hosts or via contact with antibiotic-contaminated matter within the environment. Relatively little is known about the impacts of anthropogenic disturbance on reservoirs of resistance genes in wildlife and their environments. We therefore tested for (a) antibiotic resistance genes in primate hosts experiencing different severities and types of anthropogenic disturbance (i.e., non-wildlife animal presence, human presence, direct human contact, and antibiotic treatment), and (b) covariation between host-associated and environmental resistomes. We used shotgun metagenomic sequencing of ring-tailed lemur (Lemur catta) gut resistomes and associated soil resistomes sampled from up to 10 sites: seven in the wilderness of Madagascar and three in captivity in Madagascar or the United States. We found that, compared to wild lemurs, captive lemurs harbored greater abundances of resistance genes, but not necessarily more diverse resistomes. Abundances of resistance genes were positively correlated with our assessments of anthropogenic disturbance, a pattern that was robust across all ten lemur populations. The composition of lemur resistomes was site-specific and the types of resistance genes reflected antibiotic usage in the country of origin, such as vancomycin use in Madagascar. We found support for multiple routes of ARG enrichment (e.g., via human contact, antibiotic treatment, and environmental acquisition) that differed across lemur populations, but could result in similar degrees of enrichment. Soil resistomes varied across natural habitats in Madagascar and, at sites with greater anthropogenic disturbance, lemurs and soil resistomes covaried. As one of the broadest, single-species investigations of wildlife resistomes to date, we show that the transmission and enrichment of antibiotic resistance genes varies across environments, thereby adding to the mounting evidence that the resistance crisis extends outside of traditional clinical settings.

scholarly journals Antibiotic resistance potential of the healthy preterm infant gut microbiome

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2928 ◽  
Author(s):  
Graham Rose ◽  
Alexander G. Shaw ◽  
Kathleen Sim ◽  
David J. Wooldridge ◽  
Ming-Shi Li ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Preterm Infant ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Antibiotic Resistance Genes ◽  
Taxonomic Diversity ◽  
Metagenomic Sequencing ◽  
Important Species ◽  
Antimicrobial Resistance Genes ◽  
Infant Gut Microbiome

Background Few studies have investigated the gut microbiome of infants, fewer still preterm infants. In this study we sought to quantify and interrogate the resistome within a cohort of premature infants using shotgun metagenomic sequencing. We describe the gut microbiomes from preterm but healthy infants, characterising the taxonomic diversity identified and frequency of antibiotic resistance genes detected. Results Dominant clinically important species identified within the microbiomes included C. perfringens, K. pneumoniae and members of the Staphylococci and Enterobacter genera. Screening at the gene level we identified an average of 13 antimicrobial resistance genes per preterm infant, ranging across eight different antibiotic classes, including aminoglycosides and fluoroquinolones. Some antibiotic resistance genes were associated with clinically relevant bacteria, including the identification of mecA and high levels of Staphylococci within some infants. We were able to demonstrate that in a third of the infants the S. aureus identified was unrelated using MLST or metagenome assembly, but low abundance prevented such analysis within the remaining samples. Conclusions We found that the healthy preterm infant gut microbiomes in this study harboured a significant diversity of antibiotic resistance genes. This broad picture of resistances and the wider taxonomic diversity identified raises further caution to the use of antibiotics without consideration of the resident microbial communities.

US Immigration Is Associated With Rapid and Persistent Acquisition of Antibiotic Resistance Genes in the Gut

2019 ◽  
Vol 71 (2) ◽  
pp. 419-421
Author(s):  
Quentin Le Bastard ◽  
Pajau Vangay ◽  
Eric Batard ◽  
Dan Knights ◽  
Emmanuel Montassier
Keyword(s):  
United States ◽  
Antibiotic Resistance ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Antibiotic Resistance Gene ◽  
Antibiotic Resistance Genes ◽  
The United States ◽  
Human Migration ◽  
Metagenomics Analysis

Abstract Little is known about the effect of human migration on gut microbiome antibiotic resistance gene (ARG) carriage. Using deep shotgun stool metagenomics analysis, we found a rapid increase in gut microbiome ARG richness and abundance in women from 2 independent ethnic groups relocating from Thailand to the United States.

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 Intestinal microbiota domination under extreme selective pressures characterized by metagenomic read cloud sequencing and assembly

2019 ◽  
Vol 20 (S16) ◽  
Author(s):  
Joyce B. Kang ◽  
Benjamin A. Siranosian ◽  
Eli L. Moss ◽  
Niaz Banaei ◽  
Tessa M. Andermann ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Gut Microbiome ◽  
Draft Genome ◽  
Strain Level ◽  
Comparative Genomic ◽  
Metagenomic Sequencing ◽  
Antibiotic Exposure ◽  
E Coli ◽  
Selective Pressures ◽  
Antimicrobial Resistance Genes

Abstract Background Low diversity of the gut microbiome, often progressing to the point of intestinal domination by a single species, has been linked to poor outcomes in patients undergoing hematopoietic cell transplantation (HCT). Our ability to understand how certain organisms attain intestinal domination over others has been restricted in part by current metagenomic sequencing technologies that are typically unable to reconstruct complete genomes for individual organisms present within a sequenced microbial community. We recently developed a metagenomic read cloud sequencing and assembly approach that generates improved draft genomes for individual organisms compared to conventional short-read sequencing and assembly methods. Herein, we applied metagenomic read cloud sequencing to four stool samples collected longitudinally from an HCT patient preceding treatment and over the course of heavy antibiotic exposure. Results Characterization of microbiome composition by taxonomic classification of reads reveals that that upon antibiotic exposure, the subject’s gut microbiome experienced a marked decrease in diversity and became dominated by Escherichia coli. While diversity is restored at the final time point, this occurs without recovery of the original species and strain-level composition. Draft genomes for individual organisms within each sample were generated using both read cloud and conventional assembly. Read clouds were found to improve the completeness and contiguity of genome assemblies compared to conventional assembly. Moreover, read clouds enabled the placement of antibiotic resistance genes present in multiple copies both within a single draft genome and across multiple organisms. The occurrence of resistance genes associates with the timing of antibiotics administered to the patient, and comparative genomic analysis of the various intestinal E. coli strains across time points as well as the bloodstream isolate showed that the subject’s E. coli bloodstream infection likely originated from the intestine. The E. coli genome from the initial pre-transplant stool sample harbors 46 known antimicrobial resistance genes, while all other species from the pre-transplant sample each contain at most 5 genes, consistent with a model of heavy antibiotic exposure resulting in selective outgrowth of the highly antibiotic-resistant E. coli. Conclusion This study demonstrates the application and utility of metagenomic read cloud sequencing and assembly to study the underlying strain-level genomic factors influencing gut microbiome dynamics under extreme selective pressures in the clinical context of HCT.

scholarly journals 1771. Gut Resistome Changes in Response to Prophylactic Antibiotic Administration During Chemotherapy in Children With Acute Lymphoblastic Leukemia

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S66-S66
Author(s):  
Ellie Margolis ◽  
Hana Hakim ◽  
Jiangwei Yao ◽  
Jason Rosch ◽  
Li Tang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Community Composition ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Lymphoblastic Leukemia ◽  
Metagenomic Sequencing ◽  
Pediatric Leukemia ◽  
Drug Concentrations ◽  
Stool Samples

Abstract Background Antibiotic resistance harbored in gut microbiome contributes to the emergence of multi–drug-resistant organisms (MDRO). Pediatric leukemia patients typically receive extensive antibiotics and are at higher risk for infection due to MDRO. Methods A prospective cohort of children (n = 242) with acute lymphoblastic leukemia self-collected stool samples at diagnosis and after induction chemothearpy. A third of patients (n = 69) underwent protocol-driven antibiotic prophylaxis: Levofloxacin (LV) given once neutropenia develops. With neutropenic fever patients on prophylaxis stopped LV and all patients received cefepime. Using metagenomic sequencing, we identified bacterial community composition and after alignment to the Comprehensive Antibiotic Resistance Database were able to determine the presence of bacterial resistance genes in 168 stool samples from 49 patients. Results Expected changes in the community composition were discovered with LV prophylaxis, including the loss of many Enterobacteriaceae and Enterococcaceae species, offset by increases in Bacteroides species. Unexpectedly, LV prophylaxis reduced the acquisition of VanA cluster of vancomycin resistance genes and did not increase acquisition of β-lactamase or fluoroquinolone (FQ) resistance gene families. Conclusion LV prophylaxis during leukemia treatment imparts predictable changes in gut bacterial communities but counter intuitively decreases antibiotic resistance in the gut microbiome reservoir. The reduction in VanA cluster of genes is likely due to depletion of Enterococcaceae species via direct killing or loss of synergistic partners. The lack of increase in target (FQ) or off-target resistance suggests that prophylaxis altered community selective pressures or prophylaxis drug concentrations were sufficient to limit the outgrowth of resistant mutants. Disclosures J. Wolf, Karius Inc.: Investigator, Research support.

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