scholarly journals Pneumocystis jirovecii Pneumonia in Patients with Nephrotic Syndrome: Application of Lymphocyte Subset Analysis in Predicting Clinical Outcomes

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yang Liu ◽  
Ke Zheng ◽  
Yecheng Liu ◽  
Huadong Zhu
Keyword(s):  
Nephrotic Syndrome ◽  
T Lymphocyte ◽  
Lymphocyte Count ◽  
Clinical Manifestations ◽  
Multivariate Logistic Regression Analysis ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Confirmatory Tests ◽  
Life Threatening ◽  
Hiv Negative

Purpose. With immunosuppressants being widely used, Pneumocystis jirovecii pneumonia (PCP) has been increasing and could be life-threatening among HIV-negative patients. This study aimed at identifying prognostic factors of PCP in patients with nephrotic syndrome. Methods. We retrospectively investigated patients with nephrotic syndrome who were diagnosed with PCP. The diagnosis of PCP was based on clinical manifestations, radiological findings, and microbiological confirmatory tests. Predictors of outcome were determined with multivariate logistic regression analysis. Results. A total of 57 patients were included in this study. The PCP mortality was 33.3%, which increased to 48.6% if ICU admission was required and to 60% when mechanical ventilation was needed. The T lymphocyte count and CD4/CD8 ratio independently predicted the outcome of PCP, so did the CD4+ T lymphocyte count (OR, 0.981; 95% CI, 0.967–0.996; p=0.001). The cut-off value of 71 cells/μl for the CD4+ T lymphocyte count was determined to identify patients with poor prognosis. No association was found between PCP mortality and the type of immunosuppressant used. Conclusions. PCP is a fatal complication among nephrotic syndrome patients receiving immunosuppressive therapy. The CD4+ T lymphocyte count is suggested as an independent predictor of prognosis, which can be used clinically to identify patients with high risk of unfavorable outcomes.

scholarly journals 1171. Lower Mortality with Adjuvant Corticosteroid Therapy in non-HIV Infected Patients with pneumocystis jirovecii pneumonia: A Single US Cohort Study and a Proposed Novel Mechanism of Corticosteroids

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S610-S611
Author(s):  
William Mundo ◽  
Carlos Franco-Paredes ◽  
Steven C Johnson ◽  
Leland Shapiro ◽  
Andres Henao-Martinez
Keyword(s):  
Corticosteroid Therapy ◽  
Multivariable Analysis ◽  
Solid Organ Transplantation ◽  
Pneumocystis Jirovecii ◽  
Lower Mortality ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Solid Organ ◽  
Hiv Status ◽  
Predictors Of Mortality ◽  
Hiv Negative

Abstract Background Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids given at the time of PJP antimicrobial therapy in these patients is uncertain. This study aimed to determine if corticosteroids reduced mortality in a cohort of HIV-negative PJP patients, and to propose a novel mechanism explaining corticosteroid benefit in patients regardless of HIV status. Methods We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995-2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify predictors of mortality. Results Underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), or solid organ transplantation (10.7%). Compared to HIV-positive patients, HIV-negative patients had higher rates and duration of mechanical ventilation and ICU stay. Survival was significantly increased in HIV-negative patients receiving adjunct corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (p=0.034). In an adjusted multivariable model, corticosteroids were associated with lower mortality (OR 13.5, 95% CI: 1.1-158.5, p= 0.039) regardless of HIV status. In a novel model of adjunct corticosteroid benefit, we propose corticosteroids reduce immune-mediated lysis of Pneumocystis organisms that curtails the surfactant-disabling effect of PJP internal contents. Table 1. Multivariable Analysis of Predictors of Mortality in patients with PJP Figure 1. Mortality differences by HIV status and use of steroids in PJP Conclusion We found substantial mortality among HIV-negative patients with PJP and adjunct corticosteroid use was associated with decreased mortality. Adjunct corticosteroid mortality-lowering effect is best explained by suppressing pneumocystis lysis. This reduces surfactant disruption resulting from pneumocystis internal substances. Figure 2. Proposed mechanism of action for benefits of adjunct exogenous corticosteroid therapy during PJP Disclosures All Authors: No reported disclosures

scholarly journals Lower Mortality Associated With Adjuvant Corticosteroid Therapy in Non-HIV-Infected Patients With Pneumocystis jirovecii Pneumonia: A Single-Institution Retrospective US Cohort Study

2020 ◽  
Vol 7 (9) ◽  
Author(s):  
William Mundo ◽  
Louis Morales-Shnaider ◽  
Selam Tewahade ◽  
Eric Wagner ◽  
Solana Archuleta ◽  
...  
Keyword(s):  
Solid Organ Transplantation ◽  
Case Series ◽  
Hematologic Malignancies ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Solid Organ ◽  
Retrospective Case ◽  
University Of Colorado ◽  
Beneficial Response ◽  
Hiv Negative

Abstract Background Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids in these patients is uncertain. This study aimed to determine if corticosteroids would reduce mortality in a cohort of HIV-negative PJP patients. Methods We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995 and 2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify mortality predictors. Results Common underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), and solid organ transplantation (10.7%). HIV-negative patients had higher rates and durations of mechanical ventilation and intensive care unit stay. Survival was significantly increased in HIV-negative patients receiving adjuvant corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (P = .034). In an adjusted multivariable model, no adjuvant corticosteroid use was associated with higher mortality (odds ratio, 13.5; 95% CI, 1.1–158.5; P = .039) regardless of HIV status. Conclusions We found substantial mortality among HIV-negative patients with PJP, and adjuvant corticosteroid use was associated with decreased mortality. Response to corticosteroids is best established in HIV-infected patients, but emerging reports suggest a similar beneficial response in PJP patients without HIV infection. Further prospective studies may establish a more definitive role of the addition of corticosteroids among HIV-negative patients with PJP.

scholarly journals Successful treatment of a kidney transplant patient with COVID-19 and late-onset Pneumocystis jirovecii pneumonia

2021 ◽  
Author(s):  
Jing Peng ◽  
Ming Ni ◽  
Dunfeng Du ◽  
Yanjun Lu ◽  
Juan Song ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Successful Treatment ◽  
Transplant Patient ◽  
Late Onset ◽  
Clinical Manifestations ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Kidney Transplant Patient ◽  
Transplant Patients ◽  
Kidney Transplant Patients

Abstract Background: Solid transplant patients are susceptible to Pneumocystis jirovecii pneumonia (PJP). While the vast majority of PJP cases occur within the first 6 months after transplantation, very few PJP cases are seen beyond 1 year post transplantation (late-onset PJP). PJP and coronavirus disease 2019 (COVID-19, caused by infection with SARS-CoV-2) share quite a few common clinical manifestations and imaging findings, making the diagnosis of PJP often underappreciated during the current COVID-19 pandemic. To date, only 1 case of kidney transplantation who developed COVID-19 and late-onset PJP has been reported, but this patient also suffered from many other infections and died from respiratory failure and multiple organ dysfunction syndrome. A successful treatment of kidney patients with COVID-19 and late-onset PJP has not been reported. Case presentation: We present a case of a 55-year-old male kidney transplant patient with COVID-19 who also developed late-onset PJP. He received a combined strategy, including specific anti-pneumocystis therapy, symptomatic supportive therapy, adjusted immunosuppressive therapy, and use of antiviral/antibiotics drugs, ending with a favorable outcome. Conclusions: This case highlights the importance of prompt and differential diagnosis of PJP in kidney transplant patients with SARS-CoV-2 infection. Further studies are required to clarify if kidney transplant patients with COVID-19 could be prone to develop late-onset PJP and how these patients should be treated.

scholarly journals P.103 When a neurosurgeon should care about pneumonia: the case for Pneumocystis jirovecii pneumonia prophylaxis in neurosurgical patients

2019 ◽  
Vol 46 (s1) ◽  
pp. S41
Author(s):  
M de Lotbiniere-Bassett ◽  
M Dhillon ◽  
PJ Boiteau ◽  
P Couillard
Keyword(s):  
Care Pathway ◽  
Pneumocystis Jirovecii ◽  
High Dose ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Increased Risk ◽  
Neurosurgical Patients ◽  
Preventable Harm ◽  
Dose Corticosteroid ◽  
High Index Of Suspicion ◽  
Hiv Negative

Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic interstitial fungal pneumonia. The incidence of PJP in HIV-positive populations is decreasing, while it is increasing in HIV-negative immunocompromised populations, such as neurosurgical patients treated with high-dose corticosteroids. Morbidity and mortality can be severe owing to acute respiratory failure. Methods: Two cases are described and a literature review performed to determine the incidence of PJP in the neurosurgery population. A standardized care pathway is proposed to reduce preventable harm. Results: Long-term, high-dose corticosteroid regimens (≥4 mg dexamethasone daily for ≥4 weeks) with taper are associated with increased risk of PJP infection. Additional risk factors for infection in HIV-negative patients include CNS malignancy and concurrent radiation therapy. TMP-SMX is the first-line agent for PJP prophylaxis. Conclusions: Clinicians should maintain a high index of suspicion of PJP and adopt a standardized protocol for prophylaxis in neurosurgical patients treated with high-dose corticosteroids.

Dapsone for Pneumocystis jirovecii pneumonia prophylaxis – applying theory to clinical practice with a focus on drug interactions

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Carmela Emma Corallo ◽  
John Coutsouvelis ◽  
Susan Morgan ◽  
Orla Morrissey ◽  
Sharon Avery
Keyword(s):  
Organ Transplant ◽  
Cost Effective ◽  
Chemotherapeutic Agents ◽  
Pneumocystis Jirovecii ◽  
Haematopoietic Stem Cell ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Solid Organ ◽  
Immunosuppressed Patients ◽  
Life Threatening ◽  
Substantial Risk

AbstractPneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that occurs in immunocompromised individuals. The incidence can be as high as 80% in some groups but can be reduced to less than 1% with appropriate prophylaxis. HIV-infected patients with a low CD4 count are at the highest risk of PJP. Others at substantial risk include haematopoietic stem cell and solid organ transplant recipients, those with cancer (particularly haematologic malignancies), and those receiving glucocorticoids, chemotherapeutic agents, and other immunosuppressive medications. Trimethoprim-sulfamethoxazole is an established first-line line agent for prevention and treatment of PJP. However, in some situations, this medication cannot be used and dapsone is considered a suitable cost-effective second line agent. However, information on potential interactions with drugs commonly used in immunosuppressed patients is lacking or contradictory. In this this article we review the metabolic pathway of dapsone with a focus on interactions and clinical significance particularly in patients with haematological malignancies. An understanding of this process should optimise the use of this agent.

scholarly journals Pneumocystis jirovecii pneumonia in AIDS and non-AIDS immunocompromised patients – an update

2018 ◽  
Vol 12 (10) ◽  
pp. 824-834 ◽  
Author(s):  
Yuan-Ti Lee ◽  
Ming-Lung Chuang
Keyword(s):  
Mortality Rate ◽  
Clinical Manifestations ◽  
Lactic Dehydrogenase ◽  
Diagnosis And Treatment ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Immunocompromised Patients ◽  
Aids Patients ◽  
Chain Reactions ◽  
Increased Risk

Introduction: Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an increased risk of mortality. PJ is a unique fungal pathogen which is increasingly common and maybe associated with a higher mortality rate in patients without AIDS. We present the characteristics of PJP, diagnosis, and treatment outcomes between AIDS and non-AIDS patients. Methodology: We conducted a review of studies of AIDS and non-AIDS patients with PJP using PubMed to search for studies until December 2017. Results: The annual incidence of AIDS-PJP decreased from 13.4 to 3.3 per 1000 person-years in industrialized countries, while the incidence of non-AIDS-PJP varied widely. Both groups had similar clinical manifestations and radiological features, but the non-AIDS-PJP group potentially had a more fulminant course, more diffuse ground glass opacities, and fewer cystic lesions. The mortality rate decreased in the AIDS-PJP group after the advent of antiretroviral therapy; however, the mortality rate remained high in both groups. A laboratory diagnosis was usually nonspecific; CD4+ T-cell < 200 cells/mL or < 14% favored AIDS-PJP. Serum 1,3-β-D-glucan (BDG) had a high diagnostic odds ratio. Combining BDG and lactic dehydrogenase improved the diagnosis of AIDS-PJP. Histopathological staining and polymerase chain reactions could not discriminate infection from colonization when the result was positive. The use of antibiotics, prophylaxis, and adjunctive corticosteroids was controversial. Conclusions: Early diagnosis and treatment can be achieved through vigilance, thereby improving the survival rate for PJP in immunocompromised patients.

Pneumocystis jirovecii pneumonia as a complication of etoposide therapy

2021 ◽  
Vol 14 (6) ◽  
pp. e242485
Author(s):  
Maria Alejandra Mendoza ◽  
Sunil Iyer ◽  
Jose F. Camargo ◽  
Pasquale W. Benedetto
Keyword(s):  
T Lymphocyte ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Oral Etoposide ◽  
Cellular Mechanisms

Two patients receiving oral etoposide therapy developed Pneumocystis jirovecii pneumonia during chemotherapy with significant lymphopenia without corticosteroid use. In this commentary we discuss cellular mechanisms by which etoposide induced CD4+ T lymphocyte dysfunction and reduced survival may lead to predisposition to P. jirovecii infection.

scholarly journals Detection of Pneumocystis jirovecii by Quantitative PCR To Differentiate Colonization and Pneumonia in Immunocompromised HIV-Positive and HIV-Negative Patients

2016 ◽  
Vol 54 (6) ◽  
pp. 1487-1495 ◽  
Author(s):  
T. Fauchier ◽  
L. Hasseine ◽  
M. Gari-Toussaint ◽  
V. Casanova ◽  
P. M. Marty ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Quantitative Pcr ◽  
Pneumocystis Jirovecii ◽  
Hiv Positive ◽  
Immunocompromised Patients ◽  
Infection Status ◽  
Content Type ◽  
Fungal Burden ◽  
Life Threatening ◽  
Hiv Negative

Pneumocystisjiroveciipneumonia (PCP) is an acute and life-threatening lung disease caused by the fungusPneumocystis jirovecii. The presentation of PCP in HIV-positive patients is well-known and consists of a triad of dyspnea, fever, and cough, whereas the presentation of PCP in HIV-negative patients is atypical and consists of a sudden outbreak, O2desaturation, and a rapid lethal outcome without therapy. Despite the availability of direct and indirect identification methods, the diagnosis of PCP remains difficult. The cycle threshold (CT) values obtained by quantitative PCR (qPCR) allow estimation of the fungal burden. The more elevated that the fungal burden is, the higher the probability that the diagnosis is pneumonia. The purposes of the present study were to evaluate theCTvalues to differentiate colonization and pneumonia in a population of immunocompromised patients overall and patients stratified on the basis of their HIV infection status. Testing of bronchoalveolar lavage (BAL) fluid samples from the whole population of qPCR-positive patients showed a meanCTvalue for patients with PCP of 28 (95% confidence interval [CI], 26 to 30) and a meanCTvalue for colonized patients of 35 (95% CI, 34 to 36) (P< 10−3). For the subgroup of HIV-positive patients, we demonstrated that aCTvalue below 27 excluded colonization and aCTvalue above 30 excluded PCP with a specificity of 100% and a sensitivity of 80%, respectively. In the subgroup of HIV-negative patients, we demonstrated that aCTvalue below 31 excluded colonization and aCTvalue above 35 excluded PCP with a specificity of 80% and a sensitivity of 80%, respectively. Thus, qPCR of BAL fluid samples is an important tool for the differentiation of colonization and pneumonia inP. jirovecii-infected immunocompromised patients and patients stratified on the basis of HIV infection status with differentCTvalues.

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