scholarly journals 223. Predicting Mortality Among Immunocompromised Patients Who Present With Bloodstream Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S130-S130
Author(s):  
Oryan Henig ◽  
Krishna Rao ◽  
Rosemary KB Putler ◽  
Twisha S Patel ◽  
Owen Albin ◽  
...  
Keyword(s):  
Bloodstream Infection ◽  
Risk Model ◽  
Hematologic Malignancy ◽  
Solid Organ Transplantation ◽  
Baseline Risk ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Suspected Infection ◽  
Dichotomous Variable ◽  
Definition Of

Abstract Background The revised definition of sepsis (Sepsis-3) uses Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) to identify patients with sepsis instead of systemic inflammatory response syndrome (SIRS) criteria. Subsequent studies revealed contradictory results pertaining to qSOFA, and limited data are available for immunocompromised patients. The objectives of this study were to (1) evaluate the performance of Sepsis -3 in a cohort of immunocompromised patients with microbiologically-proven sepsis, defined as having received antibiotics and having bloodstream infection (BSI); and (2) to compare its performance in the BSI cohort to its performance in immunocompromised patients who received antibiotics but did not have BSI (Non-BSI cohort). Methods Adult patients with hematologic malignancy or solid transplant recipients admitted to Michigan Medicine between 2012–2017 with suspected infection were included based on criteria used in the Sepsis-3 study: having both a body fluid culture and having received intravenous antibiotics. SOFA, qSOFA and SIRS components within 1 day of the index date (culture date or antibiotic date, whichever came first) were extracted from the medical record. For each group, a baseline risk model for mortality was created including age, gender, race, and Charlson comorbidity index. Each score (SOFA ≥ 2, qSOFA ≥ 2, SIRS ≥ 2) was added to the baseline risk model as a dichotomous variable and AUROC values were calculated. Results 2822 patients with a mean age of 56.8±15.6 were included. 349 (12.4%) had BSI. The most common immune compromising conditions were solid-organ transplantation (47%), lymphoma (21.3%) and acute leukemia (17%). 14% of patients in the BSI cohort died during hospitalization compared with 6.6% in the non-BSI cohort (P < 0.001). For the BSI cohort, when SOFA ≥ 2, qSOFA ≥ 2, SIRS ≥ 2 scores were added to the model, the AUROC values were less than those for the non-BSI cohort (table). The addition of SOFA ≥6 to the baseline risk model produced the highest AUROC values in both the BSI and non-BSI cohorts (figure). Conclusion Among immunocompromised patients, an SOFA score ≥6 was the strongest predictor of mortality. Surprisingly, sepsis scores performed better in the non-BSI cohort than in the BSI cohort. Disclosures All authors: No reported disclosures.

scholarly journals The Performance of Sepsis-3 Criteria to Predict Mortality among patients with hematologic malignancy and post-transplant who have Suspected Infection

2021 ◽  
Author(s):  
Oryan Henig ◽  
Rosemary K B Putler ◽  
Owen Albin ◽  
Twisha S Patel ◽  
Daniel Kaul ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Predictive Validity ◽  
Risk Model ◽  
Hematologic Malignancy ◽  
Positive Likelihood Ratio ◽  
Clinical Score ◽  
Baseline Risk ◽  
Immunocompromised Patients ◽  
Suspected Infection ◽  
Dichotomous Variables

Abstract Background Sepsis is a leading cause of death, particularly in immunocompromised people. The revised definition of sepsis (Sepsis-3) uses Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) to identify patients with sepsis. The aim of this study was to evaluate the performance of SOFA, qSOFA and SIRS (systemic inflammatory response syndrome) in immunocompromised patients. Methods Adult immunocompromised patients admitted to Michigan Medicine between 2012-2018 with suspected infection were included based on criteria adopted from the Sepsis-3 study. Each clinical score (SOFA≥2, qSOFA≥2, SIRS≥2) was added to the baseline risk model as an ordinal as well as dichotomous variables and AUROC values were calculated. In addition, breakpoints of SOFA between 2-10 were assessed to identify the breakpoints with the highest sensitivity and specificity for hospital mortality. The analysis was stratified for intensive care unit (ICU) status. Results Of 2822 immunocompromised patients with a mean age of 56.8±15.6, 213 (7.5%) died during hospitalization. When added to the baseline risk model, SOFA score had the greatest predictive validity for hospital mortality [AUROC=0.802 (95%CI: 0.771-0.832)], followed by qSOFA (AUROC=0.783 (0.754-0.812) and SIRS (AUROC=0.741 (0.708-0.774]). Among SOFA breakpoints that were evaluated, SOFA≥6 had the greatest predictive validity and moderate positive likelihood ratio (2.75) for hospital mortality. Conclusion The predictive validity for hospital mortality of qSOFA was similar among immunocompromised patients to that reported in the Sepsis-3 study. The sensitivity of qSOFA≥2 for hospital mortality was low. SOFA≥6 might be an effective tool to identify immunocompromised patients with suspected infection at high risk for clinical deterioration.

scholarly journals Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial

2021 ◽  
Author(s):  
Peter Bergman ◽  
Ola Blennow ◽  
Lotta Hansson ◽  
Stephan Mielke ◽  
Piotr Nowak ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Solid Organ Transplantation ◽  
Lymphocytic Leukemia ◽  
Solid Organ ◽  
Healthy Controls ◽  
Immunocompromised Patients ◽  
Hematopoietic Stem ◽  
Safety And Efficacy ◽  
Wide Range ◽  
Patient Groups

AbstractBackgroundPatients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate the safety and efficacy after two doses of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods539 study subjects (449 patients and 90 controls) were included in the clinical trial. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/chimeric antigen receptor T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.FindingsAdverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72·2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43·4%) and CLL (63·3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.InterpretationThe results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. The rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups and/or subgroups to improve immunity.FundingKnut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, Swedish Research Council, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.

scholarly journals Epitope-Level Matching—A Review of the Novel Concept of Eplets in Transplant Histocompatibility

2021 ◽  
Vol 2 (3) ◽  
pp. 336-347
Author(s):  
André Renaldo ◽  
Adriel Roa-Bautista ◽  
Elena González-López ◽  
Marcos López-Hoyos ◽  
David San Segundo
Keyword(s):  
De Novo ◽  
Graft Loss ◽  
Solid Organ Transplantation ◽  
Human Leukocyte ◽  
Future Research ◽  
Solid Organ ◽  
Leukocyte Antigen ◽  
Definition Of ◽  
Novel Concept ◽  
Hla Compatibility

The development of de novo donor-specific antibodies is related to the poor matching of the human leukocyte antigen (HLA) between donor and recipient, which leads to dismal clinical outcomes and graft loss. However, new approaches that stratify the risks of long-term graft failure in solid organ transplantation have emerged, changing the paradigm of HLA compatibility. In addition, advances in software development have given rise to a new structurally based algorithm known as HLA Matchmaker, which determines compatibility at the epitope rather than the antigen level. Although this technique still has limitations, plenty of research maintains that this assessment represents a more complete and detailed definition of HLA compatibility. This review summarizes recent aspects of eplet mismatches, highlighting the most recent advances and future research directions.

scholarly journals COVID-19 vaccine use in immunocompromised patients: A commentary on evidence and recommendations

2021 ◽  
Author(s):  
Kristine Duly ◽  
Francis A Farraye ◽  
Shubha Bhat
Keyword(s):  
Hiv Infection ◽  
Significant Proportion ◽  
Safety Data ◽  
Solid Organ Transplantation ◽  
British Society ◽  
Vaccine Hesitancy ◽  
Current Evidence ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Phase 3

Abstract Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose While COVID-19 vaccine emergency use authorization (EUA) deemed the vaccines to be effective and safe for public use, the phase 3 trials leading to EUA predominantly excluded patients with immunocompromising conditions. Immunocompromised patients make up a significant proportion of the population, and in light of recent mass vaccination efforts, we aim to review current evidence and recommendations of COVID-19 vaccines in 4 patient populations with immunocompromising disorders or conditions: human immunodeficiency virus (HIV) infection, solid organ transplantation, rheumatoid arthritis, and inflammatory bowel disease. Summary Given the evolving data on safety and efficacy of the approved COVID-19 vaccines in the immunocompromised population, it is vital that pharmacists and other immunizing providers understand the current data and recommendations and provide the public with accurate information. To date, the only immunocompromised subgroup included in phase 3 COVID-19 vaccine trials have been those with HIV infection. However, recent retrospective trials have provided reassuring safety data of the COVID-19 vaccine in immunocompromised patients, and the interim analysis of the Moderna phase 3 trial produced promising efficacy data on HIV-infected patients. Presently, the US Centers for Disease Control and Prevention, British Society for Immunology, and various other governmental and professional societies and organizations endorse COVID-19 vaccination in the immunocompromised population. Conclusion While additional data is warranted to determine the effects of immunocompromising medical conditions and immunosuppressing medications on the efficacy of the vaccine, the benefits of the vaccine is anticipated to outweigh theoretical risks. Thus, the COVID-19 vaccine is recommended to be given to immunocompromised patients at this time, and providers should make efforts to decrease vaccine hesitancy in this population through education and reassurance.

scholarly journals Gastric Mucormycosis: An Infection of Fungal Invasion into the Gastric Mucosa in Immunocompromised Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Haider A. Naqvi ◽  
Muhammad Nadeem Yousaf ◽  
Fizah S. Chaudhary ◽  
Lawrence Mills
Keyword(s):  
Abdominal Pain ◽  
Gastric Mucosa ◽  
Chronic Renal Disease ◽  
Hematologic Malignancy ◽  
Acute Onset ◽  
The Body ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Presenting Symptoms ◽  
Increased Risk

Primary gastric mucormycosis is a rare but potentially lethal fungal infection due to the invasion of Mucorales into the gastric mucosa. It may result in high mortality due to increased risk of complications in immunocompromised patients. Common predisposing risk factors to develop gastric mucormycosis are prolonged uncontrolled diabetes mellitus with or without diabetic ketoacidosis (DKA), solid organ or stem cell transplantation, underlying hematologic malignancy, and major trauma. Abdominal pain, hematemesis, and melena are common presenting symptoms. The diagnosis of gastric mucormycosis can be overlooked due to the rarity of the disease. A high index of suspicion is required for early diagnosis and management of the disease, particularly in immunocompromised patients. Radiological imaging findings are nonspecific to establish the diagnosis, and gastric biopsy is essential for histological confirmation of mucormycosis. Prompt treatment with antifungal therapy is the mainstay of treatment with surgical resection reserved in cases of extensive disease burden or clinical deterioration. We presented a case of acute gastric mucormycosis involving the body of stomach in a patient with poorly controlled diabetes and chronic renal disease, admitted with acute onset of abdominal pain. Complete resolution of lesion was noted with 16 weeks of medical treatment with intravenous amphotericin B and posaconazole.

Usefulness of ICU criteria for diagnosis of invasive pulmonary aspergillosis in nonhematologic critically ill patients

2019 ◽  
Vol 58 (3) ◽  
pp. 275-281
Author(s):  
Song-I Lee ◽  
Heungsup Sung ◽  
Sang-Bum Hong ◽  
Chae-Man Lim ◽  
Younsuck Koh ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Hematologic Malignancy ◽  
Invasive Pulmonary Aspergillosis ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Pulmonary Aspergillosis ◽  
Treatment Groups ◽  
Significant Difference ◽  
Criteria For Diagnosis

Abstract Invasive pulmonary aspergillosis (IPA) is a life-threatening disease in the intensive care unit (ICU). The ICU criteria were proposed to diagnose IPA in critically ill patients. This study aims to evaluate the usefulness of ICU criteria for diagnosis and treatment of IPA in nonhematologic patients in the ICU. We retrospectively reviewed 103 ICU patients with positive galactomannan test in blood and respiratory tract from January 1, 2016, to May 31, 2017. We excluded patients with hematologic malignancy. We divided the treatment and non-treatment groups according to the IPA treatment. We compared the baseline characteristics and outcomes between two groups and the agreement with ICU criteria. There were 49 patients in treatment groups and 54 patients in non-treatment groups. There were more cases of solid organ transplantation (P = .003), immunosuppressive therapy (P &lt; .001) and bacterial viral coinfection (P = .048) in the treatment group compared to nontreatment group. There was no statistically significant difference in mortality, the use of ventilator, and septic shock between the two groups. The agreement rate between the putative group and treatment was low (59.2%). There was no statistically significant difference in outcome between the putative and colonization groups according to the ICU criteria in each group. The treatment of IPA based on the symptom, radiologic finding and galactomannan test did not showed the better outcome. Also, the treatment based on the ICU criteria didn’t show the difference of outcome. The new criteria for diagnosis of IPA in critically ill patients are needed.

scholarly journals Definition of Opportunistic Infections in Immunocompromised Children on the Basis of Etiologies and Clinical Features: A Summary for Practical Purposes

2019 ◽  
Vol 15 (4) ◽  
pp. 197-206 ◽  
Author(s):  
Niccolò Riccardi ◽  
Gioacchino Andrea Rotulo ◽  
Elio Castagnola
Keyword(s):  
Opportunistic Infections ◽  
Immunosuppressive Treatment ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Hospitalised Patients ◽  
Nonmalignant Disease ◽  
Life Threatening ◽  
Severe Infections ◽  
Definition Of ◽  
Immunodeficiency Syndrome

: Opportunistic Infections (OIs) still remain a major cause of morbidity and death in children with either malignant or nonmalignant disease. : OIs are defined as those infections occurring due to bacteria, fungi, viruses or commensal organisms that normally inhabit the human body and do not cause a disease in healthy people, but become pathogenic when the body's defense system is impaired. OIs can also be represented by unusually severe infections caused by common pathogens. An OI could present itself at the onset of a primary immunodeficiency syndrome as a life-threatening event. More often, OI is a therapyassociated complication in patients needing immunosuppressive treatment, among long-term hospitalised patients or in children who undergo bone marrow or solid organ transplantation. : The aim of the present review is to provide a comprehensive and ‘easy to read’ text that briefly summarises the currently available knowledge about OIs in order to define when an infection should be considered as opportunistic in pediatrics as a result of an underlying congenital or acquired immune-deficit.

scholarly journals Fecal Microbiota Transplantation (FMT) for Recurrent/Refractory Clostridium difficile Infection (CDI) in Pediatric Immunocompromised Patients: A Single-center Experience

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S385-S385
Author(s):  
Natasha Kwendakwema ◽  
M Kyle Jensen ◽  
Andrew Pavia ◽  
Elizabeth Doby Knackstedt
Keyword(s):  
Clinical Data ◽  
Pediatric Patients ◽  
Fecal Microbiota Transplantation ◽  
Solid Organ Transplantation ◽  
Fecal Microbiota ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Multicenter Studies ◽  
Hematopoietic Stem ◽  
Immunosuppressive Medication

Abstract Background CDI is a common cause of bacterial diarrhea, especially in immunocompromised patients. Fecal Microbiota Transplanation (FMT) has been shown to be an effective treatment for recurrent and refractory CDI. The outcomes of FMT treatment for recurrent CDI have been well described in adult populations; however, the data for immunocompromised (IC) patients especially among children are limited. We describe the experience of FMT for treatment of CDI in immuncompromised pediatric patients. Methods We collected clinical data for IC patients &lt;21 years in our pediatric institution who had received FMT for recurrent, refractory, and/or severe CDI. IC patients included those with: solid organ transplantation (SOT) receiving immunosuppressive medications; neoplasm; hematopoietic stem cell transplantation (HSCT); inflammatory bowel disease (IBD) requiring immunosuppressive medication(s). We collected demographic and clinical data, as well as outcomes, including: resolution of diarrhea, CDI relapse, and adverse events within 3 months post-FMT. Results We performed 37 pediatric FMT for recurrent, refractory, and/or severe CDI between September 2012 and February 2017. Of these, 12 were immunocompromised children: 2 with SOT; 3 with neoplasm and/or HSCT; and 7 with IBD on immunosuppressive medication(s). Median age was 11.9 years old (range 3–16 years). 6 (50%) experienced resolution of diarrhea within 1 week post-FMT, and 9 (67%) were C. difficile negative within 3 months of FMT (3 patients did not have follow-up testing). None had CDI relapse within 3 months post-FMT. 3 (25%) had adverse event(s) within 3 months post-FMT, 2 of whom had SAEs: 1 had graft rejection at 2 months post-FMT which ultimately required re-transplantion and 1 had aspiration pneumonitis immediately following FMT. 4 (50%) of the IBD patients had disease remission (clinical, biologic, and/or histologic) in the 3 months post-FMT. Conclusion FMT appears to be effective and reasonably safe for recurrent CDI in immunocompromised pediatric patients. However, the small numbers limit conclusions, especially about safety. Larger multicenter studies are needed to precisely determine safety and efficacy in this specialized population. Disclosures All authors: No reported disclosures.

Checkpoint inhibition in immunosuppressed or immunocompromised patients with advanced cutaneous squamous cell carcinoma (CSCC): Data from prospective CemiplimAb-rwlc Survivorship and Epidemiology (C.A.S.E.) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9547-9547
Author(s):  
Guilherme Rabinowits ◽  
Soo J Park ◽  
David M. Ellison ◽  
Francis P. Worden ◽  
Rhonda W. Gentry ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Hematologic Malignancy ◽  
Objective Response ◽  
Organ Transplant ◽  
Immunosuppressed Patient ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Increased Risk ◽  
Initial Cohort

9547 Background: Immunosuppressed and/or immunocompromised patients are at increased risk for solid tumors and cutaneous malignancies. Limited data exist on the safety and effectiveness of immune checkpoint inhibitors (ICIs) in these patients because they are frequently excluded from clinical trials. Here, we describe the safety and effectiveness results from the initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC enrolled in the C.A.S.E. study (NCT03836105). Methods: C.A.S.E. is a prospective, real-world, multi-center, longitudinal study evaluating the effectiveness, safety, quality of life, and survivorship in patients with advanced CSCC treated with cemiplimab. Patients received cemiplimab 350 mg intravenously every 3 weeks per routine standard of care. Patient demographics, disease characteristics, immunosuppression, and relevant medical history were collected. Immunosuppressive regimens varied amongst patients. Investigator assessment of objective response rate (ORR), safety, and tolerability was conducted. Data from 26 immunosuppressed and/or immunocompromised patients with advanced CSCC treated with cemiplimab are presented. Recruitment is ongoing. Results: As of November 17, 2020, 121 patients were enrolled in the C.A.S.E. study, of which 26 patients (median age: 74 years [IQR: 71-84]; 85% male; 89% Caucasian) were designated as immunocompromised or immunosuppressed due to a history of solid organ transplant (n = 6), autoimmune disorder (n = 11), or hematologic malignancy (n = 9). Median duration of cemiplimab exposure was 14 months (IQR: 9.1–42, range: 0, 67). Among 19 immunocompromised or immunosuppressed patients who enrolled in C.A.S.E. prior to their third dose of cemiplimab, ORR per investigator assessment was 47% (95% CI: 24–71); 1 (5%) patient had complete response; 8 (42%) had partial response. One patient had a treatment-related serious adverse reaction of organ transplant rejection. One (3.8%) patient discontinued treatment due to increased alanine aminotransferase (not treatment-related). Immune-related AEs (irAEs) occurred in 23% of patients. No treatment-related AEs led to death. Conclusions: The safety, tolerability, and effectiveness of cemiplimab in this initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC appear to be consistent with those observed in clinical trials that excluded these patients. Further follow-up and additional data would add to our general understanding of safety and effectiveness of anti-PD1 therapy in immunocompromised and/or immunosuppressed patient populations overall. Clinical trial information: NCT03836105.

Opportunistic Fungal Infection

Chest Imaging ◽  
2019 ◽  
pp. 209-213
Author(s):  
Sonia L. Betancourt
Keyword(s):  
Fungal Infection ◽  
Opportunistic Infection ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Hematologic Malignancy ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Candida Spp ◽  
Common Opportunistic Infection ◽  
Cryptococcus Spp

Opportunistic fungal infections are caused by fungi that are nonpathogenic in the immunocompetent host, many of which are part of the normal upper respiratory tract flora. These organisms may cause pulmonary infection in immunocompromised hosts. Immunocompromised patients and patients with febrile neutropenia with opportunistic fungal infections may have normal chest radiographs. Thus, chest CT should be performed for further evaluation. Imaging abnormalities in this patient population should raise suspicion for opportunistic infection. Neutropenia is the single most important risk factor for Aspergillosis. Aspergillus is the most common opportunistic infection in patients with hematologic malignancy and bone marrow transplantation. Aspergillus spp., Candida spp., and Cryptococcus spp. are the most common fungal infections in patients with solid organ transplantation. Pneumocystis jirovecii is the most common fungal infection in patients AIDS with CD4 count s<200 cells/mm3. Cryptococcal pneumonia is also common in this population. There has been a recent increase in uncommon fungal pathogens causing invasive pulmonary disease.

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