Browsing by Author "Arshad, Mehreen"
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Item Open Access Clinical and Genomic Characterization of Recurrent Enterococcal Bloodstream Infection in Patients With Acute Leukemia.(Open Forum Infectious Diseases, 2018-06) Messina, Julia A; Sinha, Rohita; Starr, Kimberly; Arshad, Mehreen; Alexander, Barbara D; Chao, Nelson J; Sung, Anthony DRates and risk factors for recurrent enterococcal bloodstream infection (R-EBSI) and whether the same genetic lineage causes index EBSI and R-EBSI are unknown in patients with acute leukemia (AL) receiving chemotherapy.Ninety-two AL patients with EBSI from 2010 to 2015 were included. Enterococcal bloodstream infection was defined by 31 positive blood cultures for Enterococcus faecium or Enterococcus faecalis and fever, hypotension, or chills. Clearance was defined by 31 negative cultures 324 hours after last positive culture and defervescence. Recurrent enterococcal bloodstream infection was defined by a positive blood culture for Enterococcus 324 hours after clearance. Categorical variables were reported as proportions and compared by the χ2 test. Continuous variables were summarized by median and interquartile range (IQR) and compared by the Wilcoxon-Mann-Whitney Test. P values <.05 were considered significant. Whole-genome sequencing was performed on available paired BSI isolates from 7 patients.Twenty-four patients (26%) had 31 episodes of R-EBSI. Median time to R-EBSI (IQR) was 26 (13-50) days. Patients with R-EBSI had significantly longer durations of fever and metronidazole exposure during their index EBSI. Thirty-nine percent of E. faecium R-EBSI isolates became daptomycin-nonsusceptible Enterococcus (DNSE) following daptomycin therapy for index EBSI. Whole-genome sequencing analysis confirmed high probability of genetic relatedness of index EBSI and R-EBSI isolates for 4/7 patients.Recurrent enterococcal bloodstream infection and DNSE are common in patients with AL and tend to occur within the first 30 days of index EBSI. Duration of fever and metronidazole exposure may be useful in determining risk for R-EBSI. Whole-genome sequencing analysis demonstrates that the same strain causes both EBSI and R-EBSI in some patients.Item Open Access Reduction in Mortality after Umbilical Cord Blood Transplantation in Children Over a 20-Year Period (1995-2014).(Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2019-04) Spees, Lisa P; Martin, Paul L; Kurtzberg, Joanne; Stokhuyzen, Andre; McGill, Lauren; Prasad, Vinod K; Driscoll, Timothy A; Parikh, Suhag H; Page, Kristin M; Vinesett, Richard; Severyn, Christopher; Sung, Anthony D; Proia, Alan D; Jenkins, Kirsten; Arshad, Mehreen; Steinbach, William J; Seed, Patrick C; Kelly, Matthew SInfections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared 2-year all-cause and cause-specific mortality during 3 time periods based on year of transplantation (1995 to 2001, 2002 to 2007, and 2008 to 2014). We used multivariable Cox regression to identify demographic and UCBT characteristics that were associated with all-cause mortality, transplantation-related mortality, and death from invasive aspergillosis after adjustment for time period. During the 20-year study period 824 children underwent UCBT. Two-year all-cause mortality declined from 48% in 1995 to 2001 to 30% in 2008 to 2014 (P = .0002). White race and nonmalignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which GVHD (18% versus 11%; P = .06) or graft failure (9% versus 3%; P = .01) were contributory than white children. Comparing 2008 to 2014 with 1995 to 2001, more than half (59%) of the reduced mortality was attributable to a reduction in infectious mortality, with 45% specifically related to reduced mortality from invasive aspergillosis. Antifungal prophylaxis with voriconazole was associated with lower mortality from invasive aspergillosis than low-dose amphotericin B lipid complex (hazard ratio, .09; 95% confidence interval, .01 to .76). With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequentinfectious causes of death in children after UCBT. Advances in clinical practice over the past 20years improved survival of children after UCBT. Reduced mortality from infections, particularly invasive aspergillosis, accounted for the largest improvement in survival and was associated with use of voriconazole for antifungal prophylaxis.Item Open Access The gut of healthy infants in the community as a reservoir of esbl and carbapenemase- producing bacteria(Antibiotics, 2020-06-01) Saleem, Ali F; Allana, Ahreen; Hale, Lauren; Diaz, Alondra; Salinas, Raul; Salinas, Cristina; Qureshi, Shahida M; Hotwani, Aneeta; Rahman, Najeeb; Khan, Asia; Zaidi, Anita K; Seed, Patrick C; Arshad, MehreenThe recent rapid rise of multi-drug resistant Enterobacteriaceae (MDR-E) is threatening the treatment of common infectious diseases. Infections with such strains lead to increased mortality and morbidity. Using a cross-sectional study, we aimed to estimate the prevalence of gut colonization with extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae among healthy infants born in Pakistan, a setting with high incidence of MDR-E infections. Stool samples were collected from 104 healthy infants between the ages of 5 and 7 months. Enterobacteriaceae isolates were screened for resistance against several antimicrobial classes. Presence of ESBL and carbapenemase genes was determined using multiplex PCR. Sequence types were assigned to individual strains by multi-locus sequence typing. Phylogenetic analysis of Escherichia coli was done using the triplex PCR method. Forty-three percent of the infants were positive for ESBL-producing Enterobacteriaceae, the majority of which were E. coli. We identified several different ESBL E. coli sequence types most of which belonged to the phylogenetic group B2 (23%) or D (73%). The widespread colonization of infants in a developing country with ESBL-producing Enterobacteriaceae is concerning. The multiple sequence types and reported non-human sources support that multiple non-epidemic MDR lineages are circulating in Pakistan with healthy infants as a common reservoir.Item Open Access The pandemic Escherichia coli sequence type 131 strain is acquired even in the absence of antibiotic exposure.(PLoS pathogens, 2019-12-19) Whitmer, Grant R; Moorthy, Ganga; Arshad, MehreenItem Open Access Utility of Autopsy among Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: One Last Chance to Learn?(Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2018-06-09) Kelly, Matthew S; Spees, Lisa; Vinesett, Richard; Stokhuyzen, Andre; McGill, Lauren; Proia, Alan D; Jenkins, Kirsten; Arshad, Mehreen; Seed, Patrick C; Martin, Paul LAutopsy may confirm clinical diagnoses or identify conditions that were not suspected prior to a patient's death. Previous studies evaluating the utility of autopsy in hematopoietic stem cell transplant (HSCT) recipients yielded conflicting results.We conducted a retrospective cohort study of children (<18 years of age) undergoing allogeneic HSCT at Duke University who died of any cause between January 1, 1995 and December 31, 2016. We evaluated associations between patient characteristics and autopsy performance using Chi-square or Fisher's exact tests. We reviewed autopsy reports to determine the concordance between pre-autopsy causes of death and pathological diagnoses identified on autopsy. We classified unexpected diagnoses on autopsy using criteria developed by Goldman et al. We evaluated for temporal changes in the autopsy consent rate and the frequency of unexpected diagnoses on autopsy using Cochran-Armitage tests.During the 22-year study period, 475 patients died and had data available on autopsy performance, and 130 (27%) of these patients underwent autopsy. The autopsy consent rate declined over time (P<0.0001), with autopsies being performed for 40% of deaths in 1995-1999 and 17% of deaths in 2009-2016. White patients were more likely to undergo autopsy than non-white patients (P=0.03). There were no associations between autopsy performance and patient age, sex, HSCT indication, or HSCT donor. Unexpected diagnoses were identified in 31 (24%) autopsies. The proportion of autopsies with an unexpected diagnosis did not change during the study period (P=0.45). However, infectious diagnoses that would have led to a change in management were more frequently identified on autopsies in 1995-2003 than in 2004-2016 (20% vs. 0%; P=0.001).The autopsy consent rate for pediatric HSCT recipients at our institution declined substantially over the past several decades. The utility of autopsy in this patient population remains high despite a reduction in the identification of unexpected infections.