Browsing by Author "Sahasrabhojane, Pranoti"
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Item Contemporary Clinical and Molecular Epidemiology of Vancomycin-Resistant Enterococcal Bacteremia: A Prospective Multicenter Cohort Study (VENOUS I)(2021) Contreras, Germán; Munita, José; Simar, Shelby; Luterbach, Courtney; Dinh, An Q.; Rydell, Kirsten; Sahasrabhojane, Pranoti; Rios, Rafael; Díaz, Lorena; Reyes, Katherine; Zervos, Marcus; Misikir, Helina; Sánchez, Gabriela; Liu, Catherine; Doi, Yohei; Abbo, Lilian; Shimose, Luis; Seifert, Harald; Gudiol, Carlota; Barberis, Fernanda; Pedroza, Claudia; Aitken, Samuel; Shelburne, Samuel; Duin, David; Tran, Truc; Hanson, Blake; Arias, CesarBackground: Vancomycin-resistant enterococci (VRE) are major therapeutic challenges. Prospective contemporary data characterizing the clinical and molecular epidemiology of VRE bloodstream infections (BSIs) are lacking. Methods: The Vancomycin-Resistant Enterococcal BSI Outcomes Study (VENOUS I) is a prospective observational cohort of adult patients with enterococcal BSI in 11 US hospitals. We included patients with Enterococcus faecalis or Enterococcus faecium BSI with ≥1 follow-up blood culture(s) within 7 days and availability of isolate(s) for further characterization. The primary study outcome was in-hospital mortality. Secondary outcomes were mortality at days 4, 7, 10, 12, and 15 after index blood culture. A desirability of outcome ranking was constructed to assess the association of vancomycin resistance with outcomes. All index isolates were subjected to whole genome sequencing. Results: Forty-two of 232 (18%) patients died in hospital and 39 (17%) exhibited microbiological failure (lack of clearance in the first 4 days). Neutropenia (hazard ratio [HR], 3.13), microbiological failure (HR, 2.4), VRE BSI (HR, 2.13), use of urinary catheter (HR, 1.85), and Pitt BSI score ≥2 (HR, 1.83) were significant predictors of in-hospital mortality. Microbiological failure was the strongest predictor of in-hospital mortality in patients with E faecium bacteremia (HR, 5.03). The impact of vancomycin resistance on mortality in our cohort changed throughout the course of hospitalization. Enterococcus faecalis sequence type 6 was a predominant multidrug-resistant lineage, whereas a heterogeneous genomic population of E faecium was identified. Conclusions: Failure of early eradication of VRE from the bloodstream is a major factor associated with poor outcomes.Publication Multisite Detection of Tn 1549-Mediated vanB Vancomycin Resistance in Multidrug-Resistant Enterococcus faecalis ST6 in Texas and Florida(2023) Simar, Shelby; Tran, Truc; Rydell, Kirsten; Panesso, Diana; Contreras, German; Munita, Jose M.; Cifuentes. Renzo; Abbo, Lilian; Sahasrabhojane, Pranoti; Dinh, An; Axell-House, Dierdre; Savidge, Tor; Shelburne, Samuel; Hanson, Blake; Arias, CesarIn the United States, vanB-mediated resistance in enterococci is rare. We characterized three sequence type (ST) 6, vancomycin-resistant Enterococcus faecalis isolates causing bacteremia in unique patients in spatiotemporally distinct settings. Isolates were recovered between 2018 and 2020 in two cities in the United States (Houston, TX; Miami, FL). The isolates harbored the vanB operon on a chromosomally located Tn1549 transposon, and epidemiological data suggested multiple introductions of the vanB gene cluster into ST6 E. faecalis.Item Whole genome sequencing accurately identifies resistance to extended spectrum β-lactams for major gram-negative bacterial pathogens(Oxford University Press, 2017) Shelburne, Samuel; Kim, Jiwoong; Munita, José; Sahasrabhojane, Pranoti; Shields, Ryan; Press, Ellen G; Li, Xiqi; Arias, Cesar; Cantarel, Brandi; Jiang, Ying; Kim, Min; Aitken, Samuel L.; Greenberg, DavidBACKGROUND: There is marked interest in using DNA based methods to detect antimicrobial resistance (AMR) with targeted polymerase chain reaction (PCR) approaches increasingly being incorporated into clinical care. Whole genome sequencing (WGS) could offer significant advantages over targeted PCR for AMR detection, particularly for species where mutations are major drivers of AMR. METHODS: Illumina MiSeq WGS and broth microdilution (BMD) assays were performed on 90 bloodstream isolates of the four most common gram-negative bacteria causing bloodstream infections in neutropenic patients. The WGS data, including both gene presence/absence and detection of mutations in an array of AMR relevant genes, were used to predict resistance to four β-lactams commonly used in the empiric treatment of neutropenic fever. The genotypic predictions were then compared to phenotypic resistance as determined by BMD and by commercial methods during routine patient care. RESULTS: Out of 133 putative instances of resistance to the β-lactams of interest identified by WGS, only 87 (65%) would have been detected by a typical PCR based approach. The sensitivity, specificity, positive and negative predictive values for WGS in predicting AMR were 0.87, 0.98, 0.97, and 0.91 respectively. Using broth microdilution as the gold standard, our genotypic resistance prediction approach had a significantly higher positive predictive value compared to minimum inhibitory concentrations generated by commercial methods (0.97 vs. 0.92, P = 0.025). CONCLUSIONS: These data demonstrate the potential feasibility of using WGS to guide antibiotic treatment decisions for patients with life-threatening infections for an array of medically important pathogens.