scholarly journals 1100. Characterization of Enteropathogenic Escherichia coli (EPEC) in Cancer Patients With Diarrhea

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S330-S330
Author(s):  
Pablo Okhuysen ◽  
Adilene Olvera ◽  
Lily Carlin

Abstract Background Biofire FilmArray multiplexed nucleic acid amplification tests (NAAT) for bacterial diarrhea include probes specific for EPEC. However, the platform does not differentiate typical EPEC (tEPEC, defined as carrying eaeA and bfp) which have strong epidemiologic associations with diarrhea from atypical EPEC (aEPEC, carrying eaeA but not bfp) for which there is a weaker association. Nevertheless, emerging data suggest that aEPEC subsets carrying efa1/lifA which encodes for adherence factor 1/lymphocyte inhibitory factor A, are associated with diarrhea. The role of EPEC and its subtypes as agents of bacterial diarrhea have not been well defined in immunosuppressed and cancer patients. Methods We characterized EPEC subtypes in stools from healthy individuals with no diarrhea (HI, N = 21), cancer patients with diarrhea and negative NAAT (DN, N = 25) and patients with diarrhea positive NAAT for EPEC (DP, N = 54). EPEC isolated from stool cultures were tested for eaeA and bfp, stx and other E. coli pathotypes. We estimated the number of fecal EPEC using a qPCR for eaeA, efa1/lifA that detected 5.6 × 101 to 5 × 107 cfu/mg of stool. Results Demographic characteristics and underlying malignancy were similar between DN and DP groups. DP were more likely to have diarrhea on admission than DN [46/52 (88%) vs. 13/25 (52%), P < 0.01]. Stool cultures confirmed EPEC in 24/52 (60%) DP of which 23/24 (96%) were aEPEC. Fecal qPCR for eaeA confirmed EPEC in 43/52 (83%) of DP, 0/25 DN and in 3/21 (14%) of HI (P < 0.001). DP excreted a higher number of EPEC cfu/mg of stool than HI (median 168 vs. 1.18 cfu/mg, P < 0.001) and only DP excreted EPEC efa1/lifA (+) [14/52 DP (27%) vs. 0/25 DN and 0/21 HI; P < 0.001]. When compared with DP EPEC efa1/lifA (-), DP EPEC efa1/lifA (+) had a longer median duration of illness (3 days vs. 1 days, P < 0.05); more likely to be hematopoietic stem cell transplant recipients [7/14 (50%) vs. 7/38 (18%), P < 0.05] and had a higher EPEC eaeA fecal burden (median 3885 vs. 84 cfu/mg, P < 0.05). Co-infections with other pathogens were equally represented in efa1/lifA (−) and efa1/lifA (+) DP subgroups [8/14 (57%) vs. 21/38 (55%) P = NS]. Conclusion Most EPEC in cancer patients with diarrhea are aEPEC acquired in the community and when carrying efa1/lifA (+), are associated with more severe disease. Disclosures All authors: No reported disclosures.

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S394-S394
Author(s):  
Andrew Chao ◽  
Harika Yalamanchili ◽  
Eduardo Yepez Guevara ◽  
Micah Bhatti ◽  
Samuel L Aitken ◽  
...  

Abstract Background Patients with cancer are at an increased risk for C. difficile infection (CDI). A two-step approach with a Nucleic Acid Amplification Test (NAAT) followed by enzyme immunoassay (EIA) increases diagnostic sensitivity and specificity and can be used to guide antibiotic therapy. We retrospectively investigated the relative performance of the two-step approach in cancer patients with solid tumors (ST), hematologic malignancies (HS), and hematopoietic stem cell transplant recipients (HSCT). Methods We identified 204 patients with a positive NAAT test for CDI as determined by GI multiplex (Biofire) or by Illumigene (Meridian, Bioscience) in whom a reflex EIA was performed for C. difficile A/B toxins between November 2015 and February 2017. Patients were stratified into ST, HM, HSCT groups. We compared the proportion of discordant NAAT+, EIA- results among the three groups. We then compared the clinical presentation and antibiotic use for patients in the NAAT+/EIA- to those with NAAT+/EIA+ results. Results Overall an EIA+ result was found in 53 (26%) patients. The proportion of patients with NAAT+/EIA+ results was significantly different between the three lines of service; ST 31/86 (36%), HM 16/62 (26%), and HSCT 6/56 (11%) P < 0.01. A trend towards a higher proportion of positive results was observed for ST compared with the HM group (P = 0.06). Results were similar between the HM and HSCT group. However, patients in the ST were more likely to have a positive EIA when compared with HSCT patients (36% vs. 11% P < 0.01). Clinical presentation and healthcare-association were similar in all three groups regardless of the EIA result. Despite the low proportion of EIA+ confirmatory results, the majority of patients (196/204 96%) received antibiotic therapy targeting CDI. Discontinuation of CDI antibiotics prior to 10 days of therapy was similar in the EIA+ (12%) vs. EIA- (10%). Conclusion The relevance of discordant results needs to be interpreted in the context of the line of service/patient care unit. The presence of CDI as determined by NAAT/EIA is low in patients with other potential causes of diarrhea such as in HSCT recipients. A substantial proportion of cancer patients are treated unnecessarily for CDI. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S578-S579
Author(s):  
Divya S Kondapi ◽  
Sasirekha Ramani ◽  
Adilene Olvera ◽  
Robert L Atmar ◽  
Mary K Estes ◽  
...  

Abstract Background CAR-T is used to treat certain refractory hematological malignancies. B-cell aplasia and immunosuppression used to treat CAR-T side effects increase infection risk. Little data are available describing Norovirus (NoV) infections in CAR-T recipients. Methods We reviewed the medical records of 134 patients with NoV diarrhea (identified by nucleic acid amplification test) between 2016-2019. Of these patients, nine received CAR-T prior to developing NoV. Here we describe their demographics, clinical characteristics, treatments, and complications. Results The median age was 49 years (Table 1). Patients’ underlying malignancies included Non-Hodgkin’s Lymphoma (4), Acute Lymphoblastic Leukemia (3), Chronic Lymphocytic Leukemia (1) and metastatic Sarcoma (1). Prior to development of NoV, six patients had undergone hematopoietic stem cell transplant, and 1 had received checkpoint inhibitor therapy. Five patients experienced cytokine release syndrome after CAR-T, and 1 experienced CAR-T-related encephalopathy syndrome (Table 2). Two patients received interleukin-6 antagonist therapy, and one received high dose steroids. Time to diarrhea onset post-CAR-T cell infusion was variable(median 256days, IQR 26-523 days).Six had an absolute lymphocyte count< 1000/mm3 at diarrhea onset. Three had diarrhea for >14 days; median diarrhea duration in the other 6 patients was 4 days. Other GI complaints included abdominal pain (3), nausea (4), and vomiting (3). For NoV treatment, three received oral immunoglobulin, and 8 received Nitazoxanide. Complications included development of concomitant GI-GVHD(5), ileus (2), need for TPN (3), renal failure requiring dialysis (2), ICU stay (3), and death (2). Two patients were co-infected with other enteropathogens such as rotavirus, enteropathogenic and enteroaggregative E.Coli and Clostridioides difficile. Three patients with diarrhea lasting >14 days had serial samples collected over time; NoV shedding lasted 81-546 days. NoV was genotyped in 6 patients(Table 3) and included GII.2(2), GII.4(2), GII.6(1) and GII.12(1). Table 1: Patient characteristics (N=9) Table 2: CAR-T related factors Table 3: NoV Genotypes Conclusion NoV belonging to various genotypes is an important cause of acute and chronic diarrhea in patients receiving CAR-T cell therapy. Disclosures Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Robert L. Atmar, MD, Takeda Vaccines, Inc. (Grant/Research Support) Mary K. Estes, PhD, Takeda Vaccines (Consultant, Grant/Research Support)


2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 119-119
Author(s):  
Christina Reeber ◽  
Kelly Bailey ◽  
Carrie Nemec ◽  
Robert A. Salata ◽  
Kathleen Gonzalez

119 Background: At University Hospitals Seidman Cancer Center (UHSCC), adult patients with hematologic malignancies (HM) and those undergoing hematopoietic stem cell transplant (HSCT) require a central venous catheter nearly 100% of the time. According to the National Health Safety Network (NSHN), for permanent and temporary line days, the pooled mean infection rate in 2009 was 3.5 and 4.1, respectively. Catheter-associated bloodstream infections (CLABSI) lead to increased morbidity, mortality, length of stay, and cost. At UHSCC, the CLABSI rate for patients on the HM service from August 2010 through August 2011 was 8.0. Methods: It has been demonstrated that the use of Chlorhexidine (CHG) wipes has decreased the CLABSI rate in ICU and long term care patients. We were unable to identify literature evidence or medical centers currently using CHG bathing wipes in their cancer patients, specifically HSCT. A quality improvement project on the effectiveness of CHG bathing on the HSCT and HM populations commenced on April 2, 2012, at UHSCC. This study is also monitoring skin integrity to determine if there are adverse effects. Patient satisfaction is also being assessed. Results: Early results demonstrate a reduction in overall CLABSI rate to 4.3%, and no vancomycin resistant enterococcus (VRE) infections were observed since early April. Adverse effects on skin integrity have not been noted. An unanticipated obstacle is related to the “culture of bathing.” Specifically, caregivers and patients often do not understanding the importance of daily bathing as a key clinical intervention despite repeated education. The team continues to investigate this issue. Conclusions: CHG bathing appears to be an effective, well-tolerated, and minimally invasive intervention in preventing CLABSI in severely immunocompromised cancer patients. Unanticipated obstacles to implementing daily bathing have been encountered and are being addressed. During the course of this project, we also began tracking our CLABSI rate for the entire patient population on the HM HSCT nursing unit along with the service-based rate noted above.


2021 ◽  
Author(s):  
Lauren A Whitmore ◽  
Taylor Schulte ◽  
Katrin Bovbjerg ◽  
Madison Hartstein ◽  
Jane Austin ◽  
...  

Abstract Background: During, shortly after, and sometimes for years after hematopoietic stem cell transplant, a large proportion of hematological cancer patients undergoing transplant report significant physical and psychological symptoms and reduced health-related quality of life. To address these survivorship problems, we developed a low-burden, brief psychological intervention called expressive helping that includes two theory- and evidence-based components designed to work together synergistically: emotionally expressive writing and peer support writing. Building on evidence from a prior randomized control trial showing reductions in physical symptoms and distress in long-term transplant survivors with persistent survivorship problems, the Writing for Insight, Strength, and Ease (WISE) trial will evaluate the efficacy of expressive helping when used during transplant and in the early post-transplant period, when symptoms peak and when intervention could prevent development of persistent symptoms.Methods: WISE is a multi-site, two-arm randomized controlled efficacy trial. Adult hematological cancer patients scheduled for a hematopoietic stem cell transplant will complete baseline measures and then, after hospitalization but prior to transplant, they will be randomized to complete either expressive helping or a time and attention “neutral writing” task. Both expressive helping and neutral writing involve four brief writing sessions, beginning immediately after randomization and ending approximately four weeks after hospital discharge. Measures of symptom burden (primary outcome), distress, health-related quality of life, and fatigue (secondary outcomes) will be administered in seven assessments coinciding with medically relevant time points from baseline and to a year post-intervention. Discussion: The steady and continuing increase in use of stem cell transplantation has created growing need for efficacious, accessible interventions to reduce the short- and long-term negative physical and psychosocial effects of this challenging but potentially life-saving treatment. Expressive helping is a psychological intervention that was designed to fill this gap. It has been shown to be efficacious in long-term transplant survivors, but could have even greater impact if it is capable of reducing symptoms during and soon after transplant. The WISE study will evaluate these benefits in a rigorous randomized controlled trial. Trial registration: Clinicaltrial.gov: NCT03800758. Expressive Helping for Stem Cell Transplant Patients, registered January 11, 2019. https://www.clinicaltrials.gov/ct2/show/NCT03800758?term=expressive+helping&draw=2&rank=2


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S936-S936
Author(s):  
Emily Blumberg ◽  
Collins Gary ◽  
Jo-Anne H Young ◽  
Minh-Hong Nguyen ◽  
David Michonneau ◽  
...  

Abstract Background CDI is an important cause of morbidity and mortality in SOT and HCT patients (pts). In retrospective single-center analyses, severe disease and relapse were common. We undertook a multicenter prospective observational study to evaluate outcomes of CDI among both SOT and HCT patients. Methods Adults with a first episode of CDI, defined as 3 liquid stools/24 h with the detection of C. difficile toxin in stool, within the first 2 years of SOT or HCT were recruited from 12 centers internationally in the INSIGHT network. At enrollment, demographics, comorbidities, medication histories and outcomes were collected prospectively over 90 days to assess clinical cure, recurrences and complications and to define baseline risk factors for clinical cure and recurrent CDI. Results 132 patients (81 SOT, 51 HCT (32 allogeneic)) were enrolled: median age 56 years, 62.1% were males, 97% were hospitalized. 80.3% were diagnosed by DNA assay. CDI occurred a median of 20 days post transplant (IQR: 6–133). 108 patients were on PPIs. 98.5% were on antibiotics before CDI. 1st line treatment regimen was oral vancomycin in 66 patients (40 SOT, 26 HCT), metronidazole in 48 patients (27 SOT, 21 HCT), both drugs in 14 (10 SOT, 4 HCT), fidaxomicin (3) and linezolid (1). Rejection within 60 days before CDI was uncommon (6.2% SOT) as was GVHD (27.5%). 110 patients (83%, 95% CI: 46–89)) (65 SOT, 45 HCT) had clinical cure; 18% (95% CI: 11–27) had recurrent CDI, 2 were admitted to the ICU due to CDI, 11 (8.3%) died (2 HCT related to CDI). Among baselines variables, only first-line regimen was associated with a higher rate of clinical cure (P = 0.003), most notably for SOT. Factors that did not have a statistically significant negative impact on clinical cure included sex, age > 60, race, country, transplant type, steroids, diabetes, CMV viremia/disease, WBC > 15,000, creatinine > 1.5 mg/dL, or specific antibiotic given prior to CDI. Higher recurrence rates were associated with metronidazole-only regimen (OR: 4.6, 95% CI: 1.6–12.8; P = 0.004) and a history of CMV after transplant (OR: 5.2, 95% CI: 1.7–15.7; P = 0.003). Conclusion Despite their immunosuppressed state, recurrence, ICU admission and mortality occurred in a minority of SOT and HCT with CDI. Initial use of metronidazole and CMV viremia/disease were associated with higher recurrence rates. Disclosures All authors: No reported disclosures.


Pathogens ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 51 ◽  
Author(s):  
Cesar Martinez-Rodriguez ◽  
Ma. del Rocio Banos-Lara

Cancer is the first cause of death by disease in childhood globally. The most frequent types of cancers in children and adolescents are leukemias, followed by brain and central nervous system tumors and lymphomas. The recovery rate of cancer in children is around 80% in developed countries and up to 30% in developing countries. Some of the main causes of complications in children and adolescents with cancer are respiratory viral infections, mainly in bone marrow-transplanted patients. Respiratory viruses have been detected in the bronchoalveolar lavage or nasal wash specimens from cancer patients with or without respiratory illness symptoms. Human metapneumovirus (HMPV) is within the ten most common viruses that are encountered in samples from pediatric patients with underlying oncology conditions. In most of cases, HMPV is found as the only viral agent, but co-infection with other viruses or with bacterial agents has also been reported. The discrepancies between the most prevalent viral agents may be due to the different populations studied or the range of viral agents tested. Some of the cases of infection with HMPV in cancer patients have been fatal, especially in those who have received a hematopoietic stem cell transplant. This review seeks to show a general view of the participation of HMPV in respiratory illness as a complication of cancer in childhood and adolescence.


2021 ◽  
Vol 9 (6) ◽  
pp. e002630
Author(s):  
Jason D Goldman ◽  
Philip C Robinson ◽  
Thomas S Uldrick ◽  
Per Ljungman

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.


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