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  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus is an important cause of nosocomial BSI, accounting for up to 20% of BSIs in this population, with Vancomycin-resistant enterococcus (VRE) posing a particular risk. This study aims to characterize the epidemiology and outcomes of enterococcal BSIs in abdominal SOTs. Methods A retrospective, single-center, case-control study of adult abdominal organ transplant (kidney transplant (KT), liver transplant (LT), simultaneous liver-kidney transplant (SLK), pancreas transplant, or simultaneous pancreas-kidney transplant) recipients between 01/01/2016 - 07/30/2021 was conducted at Beth Israel Deaconess Medical Center. Subjects were identified and reviewed using the Organ Transplant Tracking Record, their online medical record, and Vigilanz. Subjects with an enterococcal BSI within the first 6 months post-transplant were compared to those with non-enterococcal BSIs in the same period. Results We identified 26 subjects with enterococcal BSIs and 28 controls with non-enterococcal BSIs (n = 54; 10.2%). Cases were mostly LT recipients (n = 20; 77%) with a median MELD at transplant of 33 (range 14 - 43). Controls included 8 LT recipients (29%), 14 KT recipients (50%), and 6 SLK recipients (21.4%). Groups differed significantly (all p & lt; 0.05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post-transplant. Most cases (n = 16; 62%) and 11 controls (39%) had received antibiotics within the month prior to transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p & lt; 0.0001) (Figure 1). There were no differences in 1-year mortality (Figure 2) between the groups. E. faecium was the predominant species of Enterococcus (n = 23; 88.5%), with a majority (91.3%) of the isolates being VRE. The VRE rate was 80.8% among cases, 38.9% among all BSIs, and 4.0% among all transplants. Table 1:Demographic, Surgical, Hospitalization, and Antimicrobial Data. Baseline demographic and clinical characteristics of enterococcal BSI cases and non-enterococcal BSI controls are compared, along with transplant characteristics, transfusion requirements, surgical risk factors, hospitalization data, outcomes, and antibiotic exposures. Microbiological and resistance data are also presented. Enterococcal BSIs had lower odds of being a kidney transplant and having CKD or CKD on RRT; they had higher odds of being a liver transplant and having prior immunosuppression, steroid induction alone, reoperations, and macrolide exposure. Enterococcal BSIs had lower KDPIs, higher transfusion requirements, lower cold ischemia times, more procedures, and a shorter time to BSI (Chi-square and Fischer exact tests for categorical variables; Mann-Whitney tests for continuous variables). **Liver and simultaneous liver-kidney transplants; ***Kidney and simultaneous liver-kidney transplants; ****Reoperation within two weeks of primary closure; *****Biopsy proven acute antibody or cellular rejection within 6 months of transplant; ******ERCP stenting compared to IR stenting, among those with biliary complication. BSI – bloodstream infection; CKD – chronic kidney disease; HIV – human immunodeficiency virus; MELD – model of end stage liver disease; KDPI – kidney donor profile index; CMV – cytomegalovirus; pRBC – packed red blood cells; ERCP – endoscopic retrograde cholangiopancreatography; RRT – renal replacement therapy. Figure 1:Time to Bloodstream InfectionProbability of BSI-free survival illustrated, with enterococcal BSIs occurring significantly earlier than non-enterococcal BSIs post-transplantation (Kaplan-Meier survival analysis). BSI – bloodstream infection.Figure 2:MortalityProbability of survival, without significant difference between enterococcal and non-enterococcal BSIs. Data censored at one year of follow-up. BSI – bloodstream infection. Conclusion In our abdominal organ SOTs, enterococcal BSIs occurred early among LT recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post-transplant period. Disclosures Carolyn D. Alonso, MD, Cidara Therapeutics: Advisor/Consultant|Merck: Advisor/Consultant.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2021
    In:  Human Pathology: Case Reports Vol. 23 ( 2021-03), p. 200476-
    In: Human Pathology: Case Reports, Elsevier BV, Vol. 23 ( 2021-03), p. 200476-
    Type of Medium: Online Resource
    ISSN: 2214-3300
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2834872-2
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  • 3
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 60, No. 1 ( 2019-01-02), p. 85-91
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2030637-4
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  • 4
    Online Resource
    Online Resource
    American Society of Tropical Medicine and Hygiene ; 2015
    In:  The American Journal of Tropical Medicine and Hygiene Vol. 93, No. 2 ( 2015-08-05), p. 347-349
    In: The American Journal of Tropical Medicine and Hygiene, American Society of Tropical Medicine and Hygiene, Vol. 93, No. 2 ( 2015-08-05), p. 347-349
    Type of Medium: Online Resource
    ISSN: 0002-9637 , 1476-1645
    Language: English
    Publisher: American Society of Tropical Medicine and Hygiene
    Publication Date: 2015
    detail.hit.zdb_id: 1491674-5
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  • 5
    In: JAMA, American Medical Association (AMA), Vol. 325, No. 15 ( 2021-04-20), p. 1535-
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Current Opinion in Infectious Diseases Vol. 26, No. 4 ( 2013-08), p. 326-331
    In: Current Opinion in Infectious Diseases, Ovid Technologies (Wolters Kluwer Health), Vol. 26, No. 4 ( 2013-08), p. 326-331
    Type of Medium: Online Resource
    ISSN: 0951-7375
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2026993-6
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  • 7
    Online Resource
    Online Resource
    SAGE Publications ; 2017
    In:  Annals of Pharmacotherapy Vol. 51, No. 9 ( 2017-09), p. 804-810
    In: Annals of Pharmacotherapy, SAGE Publications, Vol. 51, No. 9 ( 2017-09), p. 804-810
    Abstract: Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of bezlotoxumab (BEZ), a novel monoclonal antibody against Clostridium difficile toxin B. Data Sources: A PubMed search was conducted for data between 1946 and April 2017 using MeSH terms bezlotoxumab, MK-6072, or MDX-1388 alone and the terms Clostridium difficile combined with monoclonal antibody or antitoxin. Study Selection and Data Extraction: The literature search was limited to English-language studies that described clinical efficacy, safety, and pharmacokinetics in humans and animals. Abstracts featuring prepublished data were also evaluated for inclusion. Data Synthesis: BEZ is indicated for adult patients receiving standard-of-care (SoC) antibiotics for C difficile infection (CDI) to prevent future recurrence. Two phase III trials—MODIFY I (n = 1452) and MODIFY II (n = 1203)—demonstrated a 40% relative reduction in recurrent CDI (rCDI) with BEZ compared with placebo (16.5% vs 26.6%, P 〈 0.0001). The most common adverse drug events associated with BEZ were mild to moderate infusion-related reactions (10.3%). Conclusions: In patients treated with SoC antibiotics, BEZ is effective in decreasing rCDI. BEZ has no apparent effect on treatment of an initial CDI episode. In light of increasing rates of CDI, BEZ is a promising option for preventing recurrent episodes. The greatest benefit has been demonstrated in high-risk patients, though the targeted patient population is yet to be defined.
    Type of Medium: Online Resource
    ISSN: 1060-0280 , 1542-6270
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2053518-1
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 2011
    In:  Journal of Infection Vol. 63, No. 1 ( 2011-7), p. 1-7
    In: Journal of Infection, Elsevier BV, Vol. 63, No. 1 ( 2011-7), p. 1-7
    Type of Medium: Online Resource
    ISSN: 0163-4453
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 2012883-6
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  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. Supplement_1 ( 2021-12-04), p. S559-S560
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S559-S560
    Abstract: Immunosuppression in solid organ transplantation (SOT) increases the risk of Epstein-Barr virus (EBV) DNAemia, which may herald development of post-transplant lymphoproliferative disease (PTLD). The objective of this study was to characterize the epidemiology and risk factors for EBV DNAemia and to describe the impact of these factors on development of PTLD in a cohort of SOT recipients. Methods We retrospectively examined adult (≥18 years) SOT recipients between 1/1/2015 to 12/31/2019. Demographics, immunosuppression, and clinical outcomes were examined. Subjects were stratified as having a positive (EBV viral load & gt; 200 copies/mL) or negative viral load. Sustained EBV DNAemia was defined as EBV DNA detection ( & gt; 200 copies/mL) on at least 3 consecutive samples. Categorical variables were analyzed using chi-square or Fishers exact test. Mann-U Whitney test was used for continuous variables. Results 442 SOT recipients (258 kidney, 141 liver, 22 kidney-pancreas (KP), 15 kidney-liver, 6 pancreas) were examined. Most subjects (430, 97%) were EBV intermediate risk (recipient (R)+). 8 subjects (2%) were EBV high risk (donor (D)+, R-) and 4 (1%) were EBV low risk (D-/R-). EBV viral loads were obtained in 177/442 (40.0%) recipients. DNAemia was detected in 18/442 subjects (4.1%). It was most common in pancreas recipients(1/6; 16.7%) compared with kidney (10/258; 3.9%), liver (5/141; 3.5%), and KP recipients (1/22; 4.5%). DNAemia was most frequently observed in the D+/R- (3/8; 37.5%) group compared to intermediate risk (R+) (15/430; 3.5%) and D-/R- (0%) groups. Median time to EBV viral load detection was 14 months (range 3-60). In univariate analysis, EBV high-risk serostatus was the factor most strongly associated with development of EBV DNAemia (p & lt; 0.001). Sustained DNAemia (median viral load 1829 copies/mL; peak viral load 1.9 million copies/mL) was observed in 8 subjects (1.8%). PTLD developed in 6 subjects (1.4%); 50% had sustained DNAemia prior to diagnosis. Conclusion While uncommon, development of sustained EBV DNAemia was associated with subsequent development of PTLD in our cohort of adult SOT recipients. These data provide guidance for identifying subjects at risk for PTLD above and beyond baseline EBV high-risk serostatus. Disclosures All Authors: No reported disclosures
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 10
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 7 ( 2021-07-01)
    Abstract: The humoral immune response to Clostridioides difficile toxins in C difficile infection (CDI) is incompletely characterized in immunocompromised hosts (ICHs). Methods We conducted a prospective study of hospitalized adults with CDI, with and without immunosuppression (hematologic malignancy, active solid tumor, solid organ or stem cell transplant, inflammatory bowel disease, autoimmune disease, congenital or acquired immunodeficiency, asplenia, chronic receipt of high-dose steroids, or receipt of immunosuppressing medications within 12 months). Serum and stool antibody concentrations of immunoglobulin (Ig)M, IgG, and IgA to C difficile toxins A and B at treatment days 0, 3, and 10–14 were compared. Results Ninety-eight subjects (47 ICH; 51 non-ICH) were enrolled. Baseline serum antitoxin A and B antibody levels were similar. At day 3, ICHs demonstrated lower serum levels of antitoxin A IgG, antitoxin A IgA, and antitoxin B IgA (all P & lt; .05). At day 10–14, lower antitoxin A IgG concentrations were observed in ICHs (ICH, 21 enzyme-linked immunosorbent assay [ELISA] units; interquartile range [IQR] , 16.4–44.6) compared with non-ICH subjects (49.0 ELISA units; IQR, 21.5–103; P = .045). In stool, we observed lower concentrations of antitoxin B IgA antibodies at baseline and at day 3 for ICH subjects, with a notable difference in concentrations of antitoxin B IgA at day 3 (ICH, 6.7 ELISA units [IQR, 1.9–13.9] compared with non-ICH, 18.1 ELISA units [IQR, 4.9–31.7] ; P = .003). Conclusions The ICHs with CDI demonstrated lower levels of C difficile antitoxin antibodies in serum and stool during early CDI therapy compared with non-ICHs. These data provide insight into the humoral response to CDI in ICHs.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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