Browsing by Author "Aitken, Samuel L."
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Item Daptomycin non-susceptible Enterococcus faecium in leukemia patients: Role of prior daptomycin exposure(Elsevier, 2016) DiPippo, Adam; Tverdek, Frank; Tarrand, Jeffrey; Munita, José; Tran, Truc; Arias, Cesar; Shelburne, Samuel; Aitken, Samuel L.OBJECTIVES: We sought to determine the association between previous daptomycin exposure and daptomycin non-susceptible Enterococcus faecium (DNSEf) bloodstream infections (BSI) in adult leukemia patients. METHODS: We retrospectively identified adult (≥18 years old) leukemia patients with Enterococcus spp. bacteremia at The University of Texas MD Anderson Cancer Center (MDACC) from 6/1/2013 to 7/22/2015. Antimicrobial susceptibility and previous antibiotic exposure within the 90 days prior to bacteremia were collected. Classification and Regression Tree (CART) analysis was used to identify the most significant breakpoint between daptomycin exposure and DNSEf. RESULTS: Any amount of daptomycin received within the 90 days preceding BSI was significantly associated with isolation of DNSEf compared to daptomycin susceptible E. faecium (DSEf) (88% vs. 44%, respectively, p < 0.01). CART analysis identified receiving ≥13 days of daptomycin in the preceding 90 days as most significantly correlated with DNSEf (60% vs. 11%, relative risk [RR] 5.31, 95% Confidence interval [CI] 2.36-11.96, p < 0.01). CONCLUSIONS: Prior daptomycin exposure for ≥13 days within 90 days preceding BSI was significantly associated with isolation of DNSEf BSI in adult leukemia patients at our institution. Antimicrobial stewardship initiatives aimed at minimizing daptomycin exposure in high-risk patients may be of significant benefit in limiting the emergence of DNSEf.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.