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Longitudinal Characterization and Transmission Dynamics of Antibiotic-Resistant Organisms in an ICU (LOCATE AROs)
- Kimberley Sukhum, Candice Cass, Meghan Wallace, Caitlin Johnson, Steven Sax, Carey-Ann Burnham, Gautam Dantas, Jennie H. Kwon
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 41 / Issue S1 / October 2020
- Published online by Cambridge University Press:
- 02 November 2020, pp. s42-s43
- Print publication:
- October 2020
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Background: Healthcare-associated infections caused by antibiotic-resistant organisms (AROs) are a major cause of significant morbidity and mortality. To create and optimize infection prevention strategies, it is crucial to delineate the role of the environment and clinical infections. Methods: Over a 14-month period, we collected environmental samples, patient feces, and patient bloodstream infection (BSI) isolates in a newly built bone marrow transplant (BMT) intensive care unit (ICU). Samples were collected from 13 high-touch areas in the patient room and 4 communal areas. Samples were collected from the old BMT ICU, in the new BMT ICU before patients moved in, and for 1 year after patients moved in. Selective microbiologic culture was used to isolate AROs, and whole-genome sequencing (WGS) was used to determine clonality. Antibiotic susceptibility testing was performed using Kirby-Bauer disk diffusion assays. Using linear mixed modeling, we compared ARO recovery across time and sample area. Results: AROs were collected and cultured from environmental samples, patient feces, and BSI isolates (Fig. 1a). AROs were found both before and after a patient entered the ICU (Fig. 1b). Sink drains had significantly more AROs recovered per sample than any other surface area (P < .001) (Fig. 1c). The most common ARO isolates were Pseudomonas aeruginosa and Stenotrophomonas maltophila (Fig. 1d). The new BMT ICU had fewer AROs recovered per sample than the old BMT ICU (P < .001) and no increase in AROs recovered over the first year of opening (P > .05). Furthermore, there was no difference before versus after patients moved into the hospital (P > .05). Antibiotic susceptibility testing reveal that P. aeruginosa isolates recovered from the old ICU were resistant to more antibiotics than isolates recovered from the new ICU (Fig. 2a). ANI and clonal analyses of P. aeruginosa revealed a large cluster of clonal isolates (34 of 76) (Fig. 2b). This clonal group included isolates found before patients moved into the BMT ICU and patient blood isolates. Furthermore, this clonal group was initially found in only 1 room in the BMT ICU, and over 26 weeks, it was found in sink drains in all 6 rooms sampled (Fig. 2b). Conclusions: AROs are present before patients move into a new BMT ICU, and sink drains act as a reservoir for AROs over time. Furthermore, sink-drain P. aeruginosa isolates are clonally related to isolates found in patient BSIs. Overall, these results provide insight into ARO transmission dynamics in the hospital environment.
Funding: Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.
Disclosures: None
The Gut Microbiome and Resistome of Healthy Volunteers are Restructured After Short Courses of Antibiotics
- Winston Anthony, Kimberley Sukhum, Candice Cass, Kimberly Reske, Sondra Seiler, Tiffany Hink, Christopher Coon, Alaric D'Souza, Bin Wang, Sherry Sun, Erik Dubberke, Carey-Ann Burnham, Gautam Dantas, Jennie H. Kwon
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 41 / Issue S1 / October 2020
- Published online by Cambridge University Press:
- 02 November 2020, pp. s5-s6
- Print publication:
- October 2020
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Background: Antimicrobial exposure is a significant risk factor for the development of antibiotic-resistant organisms (ARO); however, the depth and duration of this impact is not well described. The study goal is to define impact of antibiotics on the gut microbiome of healthy volunteers (HVs). Methods: HVs were randomized to receive either 5 days of levofloxacin (LVX), azithromycin (AZM), cefpodoxime (CPD), or AZM + CPD (Fig. 1). Stool samples were collected at 15 time points per patient before, during, and after antibiotics. Remnant stool samples from the microbiology laboratory were collected from patients admitted to the medical intensive care unit (MICU) as a comparison of the microbiome in a critically ill state. DNA was extracted from samples and was submitted for shotgun sequencing. Relative abundance, resistome, and metabolic pathway abundance of bacterial taxa were determined and statistical analysis conducted in R software. Results: In total, 289 stool specimens from 20 HVs, and 26 remnant stool specimens were obtained from patients admitted from the MICU (Fig. 1). Community diversity and richness decreased in the first week post-ABX for all HVs (P < .01). Linear discriminant analysis identified Bacteroides and Clostridium as taxonomic groups enriched after CPD, while AZM and LVX produced a relative abundance increase in diverse Firmicutes spp. Longitudinal tracking confirmed that after all antibiotics except LVX, HV microbiomes lost species diversity and shifted toward a state similar to that observed in MICU patients (Fig. 2). The gut microbiome of most HVs exhibited resiliency and returned to a higher diversity level similar to their starting point; however, 10% of HVs did not. Moreover, antibiotic-specific increases in resistance markers reveal innate resistance to β-lactams and macrolides within the gut microbiome of the HVs. Finally, HV microbiomes, which shifted toward a MICU-like taxonomic state, also clustered with microbial metabolic profiles from MICU patients.
The HV microbial metabolic profiles were significantly enriched for important biosynthesis pathways producing chorismate and polysaccharides. MICU patient gut microbiomes were enriched for fatty acid regulation and quinolone biosynthesis, and for many degradation pathways important for different aspects of antibiotic resistance such as membrane integrity, alternative respiration, and antibiotic inactivation. Conclusions: Short courses of antibiotics can cause acute and chronic microbiome disruptions in HVs, as evidenced by decreased microbiome diversity and increases in specific innate resistance elements. These data support the need for antimicrobial stewardship to support rationale antibiotic use to prevent gut microbiome disruptions.
Funding: CDC BAA 200-2016-91962
Disclosures: None
2281 Prophylactic broad-spectrum antibiotics for childhood malnutrition
- Amy Elizabeth Langdon, Xiaoqing Sun, Sheila Isanaka, Gautam Dantas
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- Journal:
- Journal of Clinical and Translational Science / Volume 2 / Issue S1 / June 2018
- Published online by Cambridge University Press:
- 21 November 2018, p. 46
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OBJECTIVES/SPECIFIC AIMS: A course of oral broad-spectrum antibiotics frequently has a positive effect on morbidity and mortality in severe acute malnutrition (SAM), but the actual mechanism for this effect is unknown. This mechanism is especially important to find and quantify because of the possibility that using antibiotics prophylactically may accelerate the danger from antibiotic resistant infections. This study aims to answer (1) how antibiotic therapy improves the nutritional recovery and (2) how much it affects the prevalence of resistance genes in the microbiome. METHODS/STUDY POPULATION: Stool samples were collected from children with SAM between 6 and 60 weeks of age who received either one week of amoxicillin or placebo (n=164). The children were followed for 12 weeks with longitudinal sampling, and a subset were followed out to 2 years. All samples were frozen at −80°C and prepared for metagenome shotgun sequencing via the Illumina Nextera platform. RESULTS/ANTICIPATED RESULTS: Antibiotic treatment at the start of the nutritional program is associated with significant improvements in weight gain, mid-upper-arm circumference, and graduation from the treatment program. It is also associated with qualitative decreases in early-life fermenter Lactobacillus and known enteropathogen Campylobacter. Two years after the use of amoxicillin, the Shannon diversity index is significantly higher than that of malnourished children (effect size 0.507, 95% CI: 0.204–0.630, p=0.0007), while children who received placebo are not distinguishable from malnourished children by the same metric (effect size 0.147, 95% CI: −0.311, 0.630, p=0.5878). Sustained antibiotic resistance gene enrichment within the microbiota did not occur, as the enrichment effects disappears by week 4 of follow-up. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of amoxicillin to treat uncomplicated SAM has therapeutic benefits visible by anthropometry and by content of the gut microbiota. The main concern with the use of prophylactic antibiotics for this purpose is the effect on antibiotic resistance gene enrichment in the children’s microbiota. This concern was not supported here. The benefit/cost ratio for the use of prophylactic antibiotics for individuals in this cohort is positive when weighing effects on anthropometry, microbiome, and antibiotic resistance. The results of this study impact the treatment of millions of children each year at nutritional therapy clinics around the world.
2322: The effects of fecal microbiota transplantation on the gut microbiota in subjects with Clostridium difficile infection
- Amy Elizabeth Langdon, Christopher Bulow, Kim Reske, Sherry Sun, Tiffany Hink, Courtney Jones, Carey-Ann D. Burnham, Erik R. Dubberke, Gautam Dantas
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- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
- Published online by Cambridge University Press:
- 10 May 2018, p. 35
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OBJECTIVES/SPECIFIC AIMS: Clostridium difficile is the most common cause of infectious antibiotic associated diarrhea. It is often refractory to antimicrobial therapy and fecal microbiota transplantation (FMT) is emerging as a therapeutic option. The objective is to characterize the direct effects of FMT on the gut microbiota. METHODS/STUDY POPULATION: Fecal specimens were obtained from a cohort of 29 subjects with recurrent C. difficile infection who received FMTs from 1 of 4 healthy donors as part of a phase 2 trial (Rebiotix). Fecal specimens were collected from the subject before FMT and up to 6 months post FMT. 16S rRNA sequencing and whole-genome shotgun sequencing were used to assess microbial community composition as compared by weighted Unifrac. RESULTS/ANTICIPATED RESULTS: Before treatment, the microbial community of subjects with C. difficile infection was highly distinct from the composition of the healthy donors in terms of metabolic profile. Quantification of phylogenetic community distance from donor by weighted Unifrac distance showed a significant decrease within the 1st week (Wilcoxon rank sum, p<0.01). This metric was predictive of both treatment failures and antibiotic resistance gene count (LR=22.45, p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that distance from donor is a useful metric to quantify FMT success and that FMTs are a promising treatment for otherwise untreatable carriage of antibiotic resistance genes and organisms.