المؤلفون: Hiriart, Yanina, Scibona, Paula, Ferraris, Augusto, Belloso, Waldo H., Beruto, Valeria, Garcia Bournissen, Facundo, Zylberman, Vanesa, Muñoz, Luciana, Goldbaum, Fernando, Spatz, Linus, Colonna, Mariana, Sanguineti, Santiago, Simonovich, Ventura A.

المصدر: British Journal of Clinical Pharmacology ; volume 90, issue 4, page 1142-1151 ; ISSN 0306-5251 1365-2125

الوصف: Aims Shiga toxin‐producing Escherichia coli ‐haemolytic uraemic syndrome (STEC‐HUS) is considered a toxaemic disorder in which early intervention with neutralizing antibodies may have therapeutic benefits. INM004, composed of F (ab′) 2 fragments from equine immunoglobulins, neutralizes Stx1/Stx2, potentially preventing the onset of HUS. Methods A single‐centre, randomized, phase 1, single‐blind, placebo‐controlled clinical trial to evaluate INM004 safety, tolerance and pharmacokinetics (PK) in healthy adult volunteers, was conducted; in stage I, eight subjects were divided in two cohorts ( n = 4) to receive a single INM004 dose of 2 or 4 mg kg −1 , or placebo (INM004:placebo ratio of 3:1). In stage II, six subjects received three INM004 doses of 4 mg kg −1 repeated every 24 h, or placebo (INM004:placebo ratio of 5:1). Results Eight subjects (57.1%) experienced mild treatment‐emergent adverse events (TEAEs); most frequent were rhinitis, headache and flushing, resolved within 24 h without changes in treatment or additional intervention. No serious AEs were reported. Peak concentrations of INM004 occurred within 2 h after infusion, with median C max values of 45.1 and 77.7 μg mL −1 for 2 and 4 mg kg −1 , respectively. The serum concentration of INM004 declined in a biphasic manner ( t 1/2 range 30.7–52.9 h). Systemic exposures increased with each subsequent dose in a dose‐proportional manner, exhibiting accumulation. Geometric median C max and AUC values were 149 and 10 300 μg h mL −1 , respectively, in the repeated dose regimen. Additionally, samples from subjects that received INM004 at 2 mg kg −1 showed neutralizing capacity against Stx1 and Stx2 in in vitro assays. Conclusions The results obtained in this first‐in‐human study support progression into the phase 2 trial in children with HUS.

الإتاحة: https://doi.org/10.1111/bcp.15999Test

المؤلفون: Hiriart, Yanina, Scibona, Paula, Ferraris, Augusto, Belloso, Waldo H., Beruto, Valeria, Garcia Bournissen, Facundo, Zylberman, Vanesa, Muñoz, Luciana, Goldbaum, Fernando, Spatz, Linus, Colonna, Mariana, Sanguineti, Santiago, Simonovich, Ventura A.

المصدر: British Journal of Clinical Pharmacology; Apr2024, Vol. 90 Issue 4, p1142-1151, 10p

مصطلحات موضوعية: PHARMACOKINETICS, VOLUNTEERS, TOXINS, VOLUNTEER service, RHINITIS, IMMUNOGLOBULINS

مستخلص: Aims: Shiga toxin‐producing Escherichia coli‐haemolytic uraemic syndrome (STEC‐HUS) is considered a toxaemic disorder in which early intervention with neutralizing antibodies may have therapeutic benefits. INM004, composed of F (ab′)2 fragments from equine immunoglobulins, neutralizes Stx1/Stx2, potentially preventing the onset of HUS. Methods: A single‐centre, randomized, phase 1, single‐blind, placebo‐controlled clinical trial to evaluate INM004 safety, tolerance and pharmacokinetics (PK) in healthy adult volunteers, was conducted; in stage I, eight subjects were divided in two cohorts (n = 4) to receive a single INM004 dose of 2 or 4 mg kg−1, or placebo (INM004:placebo ratio of 3:1). In stage II, six subjects received three INM004 doses of 4 mg kg−1 repeated every 24 h, or placebo (INM004:placebo ratio of 5:1). Results: Eight subjects (57.1%) experienced mild treatment‐emergent adverse events (TEAEs); most frequent were rhinitis, headache and flushing, resolved within 24 h without changes in treatment or additional intervention. No serious AEs were reported. Peak concentrations of INM004 occurred within 2 h after infusion, with median Cmax values of 45.1 and 77.7 μg mL−1 for 2 and 4 mg kg−1, respectively. The serum concentration of INM004 declined in a biphasic manner (t1/2 range 30.7–52.9 h). Systemic exposures increased with each subsequent dose in a dose‐proportional manner, exhibiting accumulation. Geometric median Cmax and AUC values were 149 and 10 300 μg h mL−1, respectively, in the repeated dose regimen. Additionally, samples from subjects that received INM004 at 2 mg kg−1 showed neutralizing capacity against Stx1 and Stx2 in in vitro assays. Conclusions: The results obtained in this first‐in‐human study support progression into the phase 2 trial in children with HUS. [ABSTRACT FROM AUTHOR]

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المؤلفون: Park, Hyung, Tarpey, Thaddeus, Liu, Mengling, Goldfeld, Keith, Wu, Yinxiang, Wu, Danni, Li, Yi, Zhang, Jinchun, Ganguly, Dipyaman, Ray, Yogiraj, Paul, Shekhar Ranjan, Bhattacharya, Prasun, Belov, Artur, Huang, Yin, Villa, Carlos, Forshee, Richard, Verdun, Nicole C., Yoon, Hyun Ah, Agarwal, Anup, Simonovich, Ventura Alejandro, Scibona, Paula, Burgos Pratx, Leandro, Belloso, Waldo, Avendaño-Solá, Cristina, Bar, Katharine J., Duarte, Rafael F., Hsue, Priscilla Y., Luetkemeyer, Anne F., Meyfroidt, Geert, Nicola, André M., Mukherjee, Aparna, Ortigoza, Mila B., Pirofski, Liise Anne, Rijnders, Bart J.A., Troxel, Andrea, Antman, Elliott M., Petkova, Eva

المصدر: Park , H , Tarpey , T , Liu , M , Goldfeld , K , Wu , Y , Wu , D , Li , Y , Zhang , J , Ganguly , D , Ray , Y , Paul , S R , Bhattacharya , P , Belov , A , Huang , Y , Villa , C , Forshee , R , Verdun , N C , Yoon , H A , Agarwal , A , Simonovich , V A , Scibona , P , Burgos Pratx , L , Belloso , W , Avendaño-Solá , ....

مصطلحات موضوعية: /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, SDG 3 - Good Health and Well-being

الوصف: Importance: Identifying which patients with COVID-19 are likely to benefit from COVID-19 convalescent plasma (CCP) treatment may have a large public health impact. Objective: To develop an index for predicting the expected relative treatment benefit from CCP compared with treatment without CCP for patients hospitalized for COVID-19 using patients' baseline characteristics. Design, Setting, and Participants: This prognostic study used data from the COMPILE study, ie, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) evaluating CCP vs control in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. A combination of baseline characteristics, termed the treatment benefit index (TBI), was developed based on 2287 patients in COMPILE using a proportional odds model, with baseline characteristics selected via cross-validation. The TBI was externally validated on 4 external data sets: the Expanded Access Program (1896 participants), a study conducted under Emergency Use Authorization (210 participants), and 2 RCTs (with 80 and 309 participants). Exposure: Receipt of CCP. Main Outcomes and Measures: World Health Organization (WHO) 11-point ordinal COVID-19 clinical status scale and 2 derivatives of it (ie, WHO score of 7-10, indicating mechanical ventilation to death, and WHO score of 10, indicating death) at day 14 and day 28 after randomization. Day 14 WHO 11-point ordinal scale was used as the primary outcome to develop the TBI. Results: A total of 2287 patients were included in the derivation cohort, with a mean (SD) age of 60.3 (15.2) years and 815 (35.6%) women. The TBI provided a continuous gradation of benefit, and, for clinical utility, it was operationalized into groups of expected large clinical benefit (B1; 629 participants in the derivation cohort [27.5%]), moderate benefit (B2; 953 [41.7%]), and potential harm or no benefit (B3; 705 [30.8%]). Patients with preexisting conditions (diabetes, cardiovascular and pulmonary ...

وصف الملف: application/pdf

الإتاحة: https://doi.org/10.1001/jamanetworkopen.2021.47375Test
https://pure.eur.nl/en/publications/21be1451-ba59-4d26-81e4-ca00fe5103d2Test
https://pure.eur.nl/ws/files/50202263/park_2022_oi_211304_1642537124.07286.pdfTest
http://www.scopus.com/inward/record.url?scp=85123878746&partnerID=8YFLogxKTest

المؤلفون: Farizano Salazar, Diego H., Achinelli, Fernando, Colonna, Mariana, Pérez, Lucía, Giménez, Analía A., Ojeda, Maria Alejandra, Miranda Puente, Susana N., Sánchez Negrette, Lía, Cañete, Florencia, Martelotte Ibarra, Ornela I., Sanguineti, Santiago, Spatz, Linus, Goldbaum, Fernando A., Massa, Carolina, Rivas, Marta, Pichel, Mariana, Hiriart, Yanina, Zylberman, Vanesa, Gallego, Sandra, Konigheim, Brenda, Fernández, Francisco, Deprati, Matías, Roubicek, Ian, Giunta, Diego H., Nannini, Esteban, Lopardo, Gustavo, Belloso, Waldo H.

المساهمون: Kieninger, Martin, Inmunova SA, Laboratorio Elea Phoenix SA

المصدر: PLOS ONE ; volume 17, issue 9, page e0274796 ; ISSN 1932-6203

الوصف: Background Passive immunotherapy has been evaluated as a therapeutic alternative for patients with COVID-19 disease. Equine polyclonal immunotherapy for COVID-19 (EPIC) showed adequate safety and potential efficacy in a clinical trial setting and obtained emergency use authorization in Argentina. We studied its utility in a real world setting with a larger population. Methods We conducted a retrospective cohort study at “Hospital de Campaña Escuela-Hogar" (HCEH) in Corrientes, Argentina, to assess safety and effectiveness of EPIC in hospitalized adults with severe COVID-19 pneumonia. Primary endpoints were 28-days all-cause mortality and safety. Mortality and improvement in modified WHO clinical scale at 14 and 21 days were secondary endpoints. Potential confounder adjustment was made by logistic regression weighted by the inverse of the probability of receiving the treatment (IPTW) and doubly robust approach. Findings Subsequent clinical records of 446 non-exposed (Controls) and 395 exposed (EPIC) patients admitted between November 2020 and April 2021 were analyzed. Median age was 58 years and 56.8% were males. Mortality at 28 days was 15.7% (EPIC) vs. 21.5% (Control). After IPTW adjustment the OR was 0.66 (95% CI: 0.46–0.96) P = 0.03. The effect was more evident in the subgroup who received two EPIC doses (complete treatment, n = 379), OR 0.58 (95% CI 0.39 to 0.85) P = 0.005. Overall and serious adverse events were not significantly different between groups. Conclusions In this retrospective cohort study, EPIC showed adequate safety and effectiveness in the treatment of hospitalized patients with severe SARS-CoV-2 disease.

الإتاحة: https://doi.org/10.1371/journal.pone.0274796Test

المؤلفون: Lopardo, Gustavo, Belloso, Waldo H., Nannini, Esteban, Colonna, Mariana, Sanguineti, Santiago, Zylberman, Vanesa, Munoz, Luciana, Dobarro, Martín, Lebersztein, Gabriel, Farina, Javier, Vidiella, Gabriela, Bertetti, Anselmo, Crudo, Favio, Alzogaray, Maria Fernanda, Barcelona, Laura, Teijeiro, Ricardo, Lambert, Sandra, Scublinsky, Darío, Iacono, Marisa, Stanek, Vanina, Solari, Ruben, Cruz, Pablo, Casas, Marcelo Martín, Abusamra, Lorena, Luciardi, Hector Lucas, Cremona, Alberto, Caruso, Diego, Miguel, Bernardo de, Millan, Susana, Kilstein, Yael, Pereiro, Ana, Sued, Omar, Cahn, Pedro, Spatz, Linus, Goldbaum, Fernando, Pérez Lloret, Santiago

المساهمون: INM005 Study Group

المصدر: EClinicalMedicine Vol.34, 100843, 2021

مصطلحات موضوعية: COVID-19, INMUNIZACION PASIVA, ANTICUERPOS NEUTRALIZANTES, NEUMONIA, TRATAMIENTO MEDICO

الوصف: Background: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. Methods: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). Findings: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65 1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5 28% [-3 95; 14 50]; p = 0 15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14 2 (§ 0 7) days in the INM005 group and 16 3 (§ 0 7) days in the placebo group, hazard ratio 1 31 (95% CI 1 0 to 1 74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6 9% the INM005 group and 11 4% in the placebo group (risk difference [95% IC]: 0 57 [0 24 to 1 37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. Interpretation: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

وصف الملف: application/pdf

العلاقة: Lopardo, G., et al. RBD-specific polyclonal F(ab )2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease : a randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial [en línea]. Postprint del artículo publicado en: EClinicalMedicine. 2021, 34 (100843). doi:10.1016/j.eclinm.2021.100843. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/11639Test; https://repositorio.uca.edu.ar/handle/123456789/11639Test; https://doi.org/10.1016/j.eclinm.2021.100843Test

الإتاحة: https://doi.org/10.1016/j.eclinm.2021.100843Test
https://repositorio.uca.edu.ar/handle/123456789/11639Test

المؤلفون: Belloso, Waldo H.

المصدر: Therapeutic Innovation and Regulatory Science; 20240101, Issue: Preprints p1-8, 8p

مستخلص: Innovation has become an increasingly common topic in healthcare. Private companies, developers, payers, and regulators are devoting attention toward innovative products and processes as a crucial component of their interests in and occupation with healthcare services. Even when there is no consensus as to its definition, “innovation” —as opposed to “invention”— is broadly understood to refer turning a good idea into a practical solution. Adoption and applicability are key components of implementation that are sustained not only on innovation’s attributes themselves but also in the characteristics of providers, users, and implementing organizations, as well as the external environment. Regulatory agencies often face the need to make decisions about proposed innovations with obsolete or inadequate normative frameworks and with a high degree of uncertainty about its eventual performance or its risks. Early interaction between developers and dedicated multidisciplinary teams at regulatory agencies may prove instrumental for speeding up the time required for proper evaluation and product registration, as well as the establishment of quality validation mechanisms. Community involvement both in the adoption and vigilance on innovative products and processes is crucial for completing the process of defining their roles and uses.

المؤلفون: Scibona, Paula, Burgos Pratx, Leandro Daniel, Savoy, Nadia, Recart, Delfina, Elia, Yasmin, Seoane, Facundo Nahuel, Arrigo, Diego, Portalis, Maximo Rousseau, Roldan, Agustina, Cassoratti, Belen Amarilla, Diaz, Julio Cesar, Antonelli, Camila Ernestina, Perez, Lucia, Posadas-Martinez, Lourdes, Belloso, Waldo H., Simonovich, Ventura

المصدر: Transfusion and Apheresis Science ; volume 62, issue 6, page 103785 ; ISSN 1473-0502

مصطلحات موضوعية: Hematology

الإتاحة: https://doi.org/10.1016/j.transci.2023.103785Test
https://api.elsevier.com/content/article/PII:S1473050223001891?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1473050223001891?httpAccept=text/plainTest

المؤلفون: Achhra, Amit C., Mocroft, Amanda, Ross, Michael, Ryom-Nielson, Lene, Avihingsanon, Anchalee, Bakowska, Elzbieta, Belloso, Waldo, Clarke, Amanda, Furrer, Hansjakob, Lucas, Gregory M., Ristola, Matti, Rassool, Mohammed, Ross, Jonathan, Somboonwit, Charurut, Sharma, Shweta, Wyatt, Christina, INSIGHT START Study Grp

المساهمون: Clinicum, Department of Medicine, Infektiosairauksien yksikkö, HUS Inflammation Center

مصطلحات موضوعية: HIV, Kidney, CKD, HAART, eGFR, START, CHRONIC KIDNEY-DISEASE, INFECTED PATIENTS, SERUM CREATININE, TENOFOVIR, RISK, IMMUNODEFICIENCY, NEPHROPATHY, ASSOCIATION, COBICISTAT, VARIANTS, 3121 General medicine, internal medicine and other clinical medicine, 317 Pharmacy, 1183 Plant biology, microbiology, virology

الوصف: The impact of early ART initiation (versus deferring) on kidney function has not been studied. START was a randomised comparison of immediate versus deferred ART initiation among HIV-positive persons with CD4(+) (cellsimm(3)) counts >500. Serum creatinine and urine dipstick protein were measured at Months 0, 1, 4, 8 and 12, and annually thereafter. The two arms were compared for changes in eGFR (mL/min/1.73 m(2), calculated by CI94% and >19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over 2.1 years median follow-up, mean eGFR was 056 (95% CI 0.003-1.11) higher in the immediate versus deferred arm, which was more prominent after adjustment for current tenofovir or bPI use (1.85, 95% CI 1.21-2.50) and in Black participants (30.1% overall) (3.90, 95% CI 2.84-4.97) versus non-Blacks (1.05, 95% CI 0.33-1.77) (P <0.001 for interaction). Relative risk for proteinuria in the immediate versus deferred arm was 0.74 (95% CI 0.55-1.00) (P = 0.049). In the short-term, immediate ART initiation was associated with a modestly higher eGFR and lower proteinuria risk versus deferring ART (more pronounced in Black participants). Whether this early benefit translates into a lower risk of CKD requires further follow-up. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. ; Peer reviewed

وصف الملف: application/pdf

العلاقة: This work was supported by the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases [UM1 AI 068641, UM1-A1120197]: the Department of Bioethics at the NIH Clinical Center: the National Cancer Institute: the National Heart, Lung, and Blood Institute; the National Institute of Mental Health; the National Institute of Neurological Disorders and Stroke; and the National Institute of Arthritis and Musculoskeletal Disorders. Financial support for START was also provided by the French Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS); the Federal Ministry of Education and Research; the European AIDS Treatment Network (NEAT): the National Health and Medical Research Council; and Medical Research Council and National Institute for Health Research. Six pharmaceutical corn panics (AbbVie, Inc., Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, LLC, and Merck Sharp and Dohme Corp.) donate antiretroviral drugs to START. The authors were also supported by the National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK100272, P01 DK056492 and R01 DK112258 to CW] and the National Institute on Drug Abuse [K24 DA035684, R01 DA026770 to GML].; Achhra , A C , Mocroft , A , Ross , M , Ryom-Nielson , L , Avihingsanon , A , Bakowska , E , Belloso , W , Clarke , A , Furrer , H , Lucas , G M , Ristola , M , Rassool , M , Ross , J , Somboonwit , C , Sharma , S , Wyatt , C & INSIGHT START Study Grp 2017 , ' Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial ' , International Journal of Antimicrobial Agents , vol. 50 , no. 3 , pp. 453-460 . https://doi.org/10.1016/j.ijantimicag.2017.04.021Test; ORCID: /0000-0001-5115-2811/work/40580735; 85027254683; f31c9579-4d4d-4d2d-a1a6-ae45e335c825; http://hdl.handle.net/10138/298136Test; 000408686800024

الإتاحة: http://hdl.handle.net/10138/298136Test

المؤلفون: Wyman Engen, Nicole, Huppler Hullsiek, Kathy, Belloso, Waldo H, Finley, Elizabeth, Hudson, Fleur, Denning, Eileen, Carey, Catherine, Pearson, Mary, Kagan, Jonathan

المساهمون: National Institute of Allergy and Infectious Diseases

المصدر: Clinical Trials ; volume 17, issue 1, page 3-14 ; ISSN 1740-7745 1740-7753

الوصف: Background: Evidence from prospectively designed studies to guide on-site monitoring practices for randomized trials is limited. A cluster randomized study, nested within the Strategic Timing of AntiRetroviral Treatment (START) trial, was conducted to evaluate on-site monitoring. Methods: Sites were randomized to either annual on-site monitoring or no on-site monitoring. All sites were centrally monitored, and local monitoring was carried out twice each year. Randomization was stratified by country and projected enrollment in START. The primary outcome was a participant-level composite outcome including components for eligibility errors, consent violations, use of antiretroviral treatment not recommended by protocol, late reporting of START primary and secondary clinical endpoints (defined as the event being reported more than 6 months from occurrence), and data alteration and fraud. Logistic regression fixed effect hierarchical models were used to compare on-site versus no on-site monitoring for the primary composite outcome and its components. Odds ratios and 95% confidence intervals comparing on-site monitoring versus no on-site monitoring are cited. Results: In total, 99 sites (2107 participants) were randomized to receive annual on-site monitoring and 97 sites (2264 participants) were randomized to be monitored only centrally and locally. The two monitoring groups were well balanced at entry. In the on-site monitoring group, 469 annual on-site monitoring visits were conducted, and 134 participants (6.4%) in 56 of 99 sites (57%) had a primary monitoring outcome. In the no on-site monitoring group, 85 participants (3.8%) in 34 of 97 sites (35%) had a primary monitoring outcome (odds ratio = 1.7; 95% confidence interval: 1.1–2.7; p = 0.03). Informed consent violations accounted for most outcomes in each group (56 vs 41 participants). The largest odds ratio was for eligibility violations (odds ratio = 12.2; 95% confidence interval: 1.8–85.2; p = 0.01). The number of participants with a late START primary ...

الإتاحة: https://doi.org/10.1177/1740774519881616Test

المؤلفون: Blumberg, Emily, Gary, Collins, Young, Jo-Anne H, Nguyen, Minh-Hong, Michonneau, David, Temesgem, Zelalem, Origuen, Julia, Barcan, Laura, Obeid, Karam, Belloso, Waldo, Gras, Julien, Corbelli, Giulio Maria, Neaton, James, Lundgren, Jens, Snydman, David R, Molina, Jean-michel

المصدر: Open Forum Infectious Diseases ; volume 6, issue Supplement_2, page S936-S936 ; ISSN 2328-8957

مصطلحات موضوعية: Infectious Diseases, Oncology

الوصف: 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% ...

الإتاحة: https://doi.org/10.1093/ofid/ofz360.2348Test
http://academic.oup.com/ofid/article-pdf/6/Supplement_2/S936/30270961/ofz360.2348.pdfTest