scholarly journals 1404. The FilmArray Meningitis/Encephalitis (FA ME) May Be of Higher Yield in the Immunocompromised Patient Population

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S511-S511
Author(s):  
Nirja Mehta ◽  
Jesse T Jacob ◽  
Christina Dean ◽  
Zanthia Wiley ◽  
Eileen Burd ◽  
...  
Keyword(s):  
Cryptococcal Meningitis ◽  
Chart Review ◽  
Hematologic Malignancy ◽  
False Negative ◽  
Small Sample ◽  
Cns Infection ◽  
Steady Increase ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Immunocompetent Patients

Abstract Background The FilmArray® Meningitis/Encephalitis (FA ME) panel is a PCR-based assay that rapidly detects 14 pathogens directly from CSF specimens. After the introduction of this assay at our institution, there was a steady increase in requests for use; however, the positivity rate remained stable. We sought to understand the characteristics of the patients most likely to have a positive FA ME panel, with particular interest in the immune status of each patient. Methods A retrospective chart review was conducted on 124 patients with suspected infectious meningitis/encephalitis at a large academic tertiary referral center who received FA ME testing between October 2016 and November 2018. Patients were considered immunocompromised if they had received chemotherapy, were solid-organ transplant recipients, or were diagnosed with HIV, autoimmune diseases on immunosuppressants, uncontrolled diabetes, cirrhosis, or hematologic malignancy. Clinical CNS infection was determined using chart review based on culture, serologic, or molecular data. Results 60 (48%) patients were immunocompromised and 64 (52%) patients were immunocompetent. Clinical CNS infection occurred in ~25% of immunocompetent (17, 26%) and immunocompromised (17, 28%) patients. However, only 6 immunocompetent patients were found to have a positive FA ME; this accounts for only 35% of the total number of positive FA ME assays during this study period (P = 0.08). Notably, 4 out of 6 patients with cryptococcal meningitis had false-negative results on the FA ME. Conclusion In spite of the relatively small sample size, there was a trend toward significance in the accurate yield of the FA ME panel in the immunocompromised population compared with the immunocompetent. Our immunocompromised patients appear to be more likely to have an infection which is tested for on the panel. The rates of confirmed CNS infections in both populations were very similar, indicating that immunocompromised patients may benefit more from use of this assay. In our study, immunocompetent patients were more likely to have West Nile infection, for example, which is not on the panel. Additionally, had cryptococcal meningitis been accurately diagnosed by the FA ME, an even greater number of immunocompromised patients would have had a positive FA ME. Disclosures All authors: No reported disclosures.

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.

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.

scholarly journals Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections

2020 ◽  
Vol 9 (2) ◽  
pp. 331 ◽  
Author(s):  
Sébastien Lhomme ◽  
Olivier Marion ◽  
Florence Abravanel ◽  
Jacques Izopet ◽  
Nassim Kamar
Keyword(s):  
Hepatitis E Virus ◽  
Hematologic Malignancy ◽  
Antiviral Treatment ◽  
Clinical Manifestations ◽  
Hepatitis E ◽  
Immunosuppressive Drugs ◽  
New Drugs ◽  
Renal Diseases ◽  
Solid Organ ◽  
Immunocompromised Patients

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis throughout the world. Most infections are acute but they can become chronic in immunocompromised patients, such as solid organ transplant patients, patients with hematologic malignancy undergoing chemotherapy and those with a human immunodeficiency virus (HIV) infection. Extra-hepatic manifestations, especially neurological and renal diseases, have also been described. To date, four main genotypes of HEV (HEV1-4) were described. HEV1 and HEV2 only infect humans, while HEV3 and HEV4 can infect both humans and animals, like pigs, wild boar, deer and rabbits. The real epidemiology of HEV has been underestimated because most infections are asymptomatic. This review focuses on the recent advances in our understanding of the pathophysiology of acute HEV infections, including severe hepatitis in patients with pre-existing liver disease and pregnant women. It also examines the mechanisms leading to chronic infection in immunocompromised patients and extra-hepatic manifestations. Acute infections are usually self-limiting and do not require antiviral treatment. Conversely, a chronic HEV infection can be cleared by decreasing the dose of immunosuppressive drugs or by treating with ribavirin for 3 months. Nevertheless, new drugs are needed for those cases in which ribavirin treatment fails.

scholarly journals Clinical Characteristics and Radiologic Features of Immunocompromised Patients With Pauci-Bacillary Pulmonary Tuberculosis Receiving Delayed Diagnosis and Treatment

2019 ◽  
Vol 6 (2) ◽  
Author(s):  
Joung Ha Park ◽  
Jooae Choe ◽  
Moonsuk Bae ◽  
Sungim Choi ◽  
Kyung Hwa Jung ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Hematologic Malignancy ◽  
Diagnostic Delay ◽  
Organ Transplant ◽  
Delayed Diagnosis ◽  
Tertiary Hospital ◽  
The Other ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Radiologic Features

Abstract Background Pauci-bacillary pulmonary tuberculosis (TB) can be delayed to diagnose and start anti-TB therapy, especially in immunocompromised patients. We therefore evaluated the clinical and radiologic features of these delayed cases. Methods Immunocompromised adult patients with pauci-bacillary pulmonary TB were retrospectively enrolled in a tertiary hospital in an intermediate–TB burden country over a 5-year period. We defined “missed TB” or “not-missed TB” patients as those who started anti-TB therapy after or before positive mycobacterial culture results, respectively. Results Of 258 patients, 134 (52%) were classified in the missed TB group, and 124 (48%) in the not-missed TB group. Positive results of molecular tests including MTB polymerase chain reaction and/or Xpert TB/RIF were only obtained in the not-missed TB group (54/106, 54%). The median diagnostic delay in the missed TB group was longer than in the other group (30 vs 6 days; P < .001). In the missed TB group, the most common working diagnoses were pneumonia (46, 34%) and lung metastasis of malignancy (40, 30%). Typical radiologic findings for TB, such as upper lobe predominance and centrilobular nodules with tree-in-bud appearance, were less common in the missed TB group than in the other group. Old age (odds ratio [OR], 1.03), solid organ transplant (OR, 3.46), solid tumor (OR, 3.83), and hematologic malignancy (OR, 4.04) were independently associated with missed TB. Conclusions Care is needed to differentiate pauci-bacillary TB, especially in immunocompromised patients with the mentioned risk factors, even without the usual radiologic features of TB. Additional rapid diagnostic tests to rule out pauci-bacillary TB are urgently needed.

scholarly journals A fatal case of meningitis caused by Cryptococcus neoformans var. grubii in an immunocompetent male

2010 ◽  
Vol 5 (01) ◽  
pp. 071-074 ◽  
Author(s):  
Prashant Gupta ◽  
Shruti Malik ◽  
Vineeta Khare ◽  
Gopa Banerjee ◽  
Anurag Mehrotra ◽  
...  
Keyword(s):  
Developing Countries ◽  
Cryptococcus Neoformans ◽  
Cryptococcal Meningitis ◽  
Fatal Case ◽  
Immunocompromised Patients ◽  
Course Of Illness ◽  
Cryptococcal Infection ◽  
Immunocompetent Patients

The incidence of cryptococcal infection is high in developing countries such as India. Cryptococcal meningitis is considered rare in immunocompetent patients and is mainly a disease of immunocompromised patients. Prognosis in immunocompetent patients is generally considered good. We report a fatal case of cryptococcal meningitis in an immunocompetent male caused by Cryptococcus neoformans var. grubii. Whether the patient is immunocompromised or immunocompetent, the outcome of the disease can be severe unless the disease is diagnosed early in the course of illness.

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 Retrospective Study of Cryptococcal Meningitis With Elevated Minimum Inhibitory Concentration to Fluconazole in Immunocompromised Patients

2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Hashem Nasri ◽  
Sarah Kabbani ◽  
Melhim Bou Alwan ◽  
Yun F. Wang ◽  
Paulina A. Rebolledo ◽  
...  
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Maintenance Therapy ◽  
Cryptococcal Meningitis ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
Organ Transplant ◽  
Retrospective Chart Review ◽  
High Dose ◽  
Solid Organ ◽  
Immunocompromised Patients

Abstract Background.  Mortality for cryptococcal meningitis remains significant, in spite of available treatment. Resistance to first-line maintenance therapy, particularly fluconazole, has been reported. Methods.  A retrospective chart review was performed on immunocompromised patients with cryptococcal meningitis, who had susceptibility testing performed between January 2001 and December 2011, at 3 hospitals in Atlanta, Georgia. Results.  A total of 35 immunocompromised patients with cryptococcal meningitis were identified, 13 (37.1%) of whom had an elevated minimum inhibitory concentration (MIC) to fluconazole (MIC ≥16 µg/mL). Eighty percent of patients were males with African American predominance, the median age was 37 years, and 80% of the patients were human immunodeficiency virus (HIV) positive. Subsequent recurrence of cryptococcal meningitis was more likely in HIV patients compared with solid organ transplant patients (P = .0366). Overall, there was a statistically significant increase in an elevated MIC to fluconazole in patients who had a history of prior azole use (odds ratio, 10.12; 95% confidence interval, 2.04–50.16). Patients with an elevated MIC to fluconazole and those with a high cerebrospinal fluid cryptococcal antigen load (≥1:512) were more likely to have central nervous system complications (P = .0358 and P = .023, respectively). Although no association was observed between an elevated MIC to fluconazole and mortality, those who received voriconazole or high-dose fluconazole (≥800 mg) for maintenance therapy were more likely to survive (P = .0288). Conclusions.  Additional studies are required to further investigate the morbidity and mortality associated with an elevated MIC to fluconazole in cryptococcal meningitis, to determine when it is appropriate to perform susceptibility testing, and to evaluate its cost effectiveness.

scholarly journals DAS181 Treatment of Severe Lower Respiratory Tract Parainfluenza Virus Infection in Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study

2021 ◽  
Author(s):  
Roy F Chemaly ◽  
Francisco M Marty ◽  
Cameron R Wolfe ◽  
Steven J Lawrence ◽  
Sanjeet Dadwal ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Tract ◽  
Primary Endpoint ◽  
Lower Respiratory Tract ◽  
Parainfluenza Virus ◽  
Controlled Study ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. Methods Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. Results A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). Conclusions The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877.

scholarly journals 735. Trends and Cost Analysis of Aspergillus Galactomannan testing at a Tertiary Medical Center

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S417-S417
Author(s):  
Peyton R Treutel ◽  
Anna Carr ◽  
Pradeep Bathina
Keyword(s):  
Stem Cell ◽  
Hematologic Malignancy ◽  
Medical Center ◽  
Organ Transplant ◽  
The Self ◽  
Solid Organ ◽  
Data Set ◽  
Hematopoietic Stem ◽  
Patients Âgés ◽  
Optical Density Index

Abstract Background Aspergillus is a fungus spread by inhalation of spores that can lead to invasive (IA), chronic, or allergic aspergillosis. Risk factors for IA include neutropenia, hematological malignancy, allogenic stem cell (HSCT) or solid organ transplant, severe immunodeficiency, or prolonged steroid use. An alternative to invasive tissue sampling, the serum Galactomannan (AGM) test detects a polysaccharide cell wall component of Aspergillus and can be used to determine a probable diagnosis of IA. Accuracy of AGM is related to disease burden and thus has the highest sensitivity and specificity in patients with hematologic malignancy or Hematopoietic stem cell transplantation (HSCT) at 70-82% and 86-92%, respectively. Studies have shown sensitivity to decline in other populations, with solid organ transplants as low as 20%. Methods We performed a retrospective study of all patients who received the AGM test at UMMC from January 3, 2013 to December 31, 2019. Patient Cohort Explorer was used to obtain de-identified patient data from EPIC. We obtained the number of encounters and patients on whom the AGM test was performed along with other variables. Billing offices provided the self-pay cost per AGM test. Results A total of 6,404 AGM tests were performed on 2,126 patients during 4,315 encounters in the study period. With a total of 499, 574, 984, 1140, 851, 1175 and 1181 tests done respectively from 2013 to 2019, a increasing trend was noted. The patients ages ranged from 1 to 89 with a median age of 52 years. A total of 3,055 tests were ordered in females, and 3,349 were ordered in males. At a cut off value (optical density index) of &gt; 0.5, 183 AGM tests resulted positive in 108 patients and at a cut of &gt; 1.0, 113 tests are positive in 70 patients. The rate of a positive AGM tests at &gt; 0.5 was at 2.85% and at &gt; 1.0 was at 1.76% over the study period. With the self-pay cost of each test at $134.54 in 2019 USD, the total cost of 6,404 tests was $861,594.16. Conclusion To our knowledge this data set constitutes the largest sample size of AGM testing. From our data, it seems that the rate of ordering this test has increased yearly. Relatively low percentage of these tests are positive, suggesting that it is most likely a large amount of these tests could have been ordered inappropriately or in the wrong clinical context. Disclosures All Authors: No reported disclosures

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