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.

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 Evaluation of a Turbidimetric β-D-Glucan Test for Detection of Pneumocystis jirovecii Pneumonia

2018 ◽  
Vol 56 (7) ◽  
pp. e00286-18 ◽  
Author(s):  
Karl Dichtl ◽  
Ulrich Seybold ◽  
Johannes Wagener
Keyword(s):  
Sensitivity And Specificity ◽  
Test Performance ◽  
Laboratory Diagnosis ◽  
Turnover Time ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Content Type ◽  
Increased Risk ◽  
Turbidimetric Assay ◽  
Respiratory Specimens

ABSTRACT Currently, diagnosis of Pneumocystis jirovecii pneumonia (PJP) relies on analysis of lower respiratory specimens, either by microscopy or quantitative real-time PCR (qPCR). Thus, bronchoscopy is required, which is associated with increased risk of respiratory failure. We assessed the value of noninvasive serologic β-d-glucan (BDG) testing for laboratory diagnosis of PJP using a newly available turbidimetric assay. We identified 73 cases of PJP with positive qPCR results from lower respiratory specimens for Pneumocystis and serology samples dating from 1 week before to 4 weeks after qPCR. In addition, 25 sera from controls with suspected PJP but specimens negative for Pneumocystis by qPCR were identified. Sera were tested with a turbidimetric BDG assay (Fujifilm Wako Chemicals Europe GmbH, Neuss, Germany), using an 11-pg/ml cutoff. Sensitivity and specificity were calculated based on qPCR test results as a reference. The turbidimetric BDG assay identified 63/73 patients with positive or slightly positive qPCR tests for an overall sensitivity of 86%; after exclusion of cases with only slightly positive qPCR results, sensitivity was 91%. No correlation between serum BDG levels and respiratory specimen DNA levels was found. Serologic BDG testing was negative in 25/25 controls with negative qPCR for a specificity of 100% using the predefined cutoff. In 22/25 samples (88%), no BDG was detected. Serologic BDG testing using the turbidimetric assay showed high sensitivity and specificity compared to qPCR of lower respiratory specimens for the diagnosis of PJP. Both turnover time and test performance will allow clinicians to delay or in some cases forego bronchoscopy.

scholarly journals P54 Pneumocystis jirovecii prophylaxis in patients on rituximab

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_4) ◽  
Author(s):  
Kishore Warrier1 ◽  
Catherine Salvesani ◽  
Samundeeswari Deepak
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Pneumocystis Jirovecii ◽  
Current Evidence ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Number Of Patients ◽  
Increased Risk

Abstract Background Rituximab is a chimeric monoclonal antibody that depletes the B cell population by targeting cells bearing the CD20 surface marker and is used widely in the management of paediatric rheumatological conditions like juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), mixed connective tissue disease (MCTD) and juvenile idiopathic arthritis (JIA). Pneumocystis jirovecii pneumonia (PCP) is a potentially fatal opportunistic infection associated with congenital and acquired defects in T cell–mediated immunity. Our guideline did not recommend prophylaxis against PCP for patients on rituximab, unlike patients on cyclophosphamide, who are on cotrimoxazole until three months after cessation of the treatment. Cyclophosphamide is an alkylating agent which affects both B and T lymphocytes. Following the death of 16 year-old girl with JSLE due to PCP, the team reviewed the possible contributing factors, undertook a review of literature and discussed this at multi-disciplinary meetings involving the microbiology and immunology teams. This patient was found to have other risk factors for PCP – low CD4 T cells, concomitant use of corticosteroids and hypogammaglobulinaemia (IgG 3.0g/L). Although there is limited evidence that rituximab on its own increases the risk of PCP, there is emerging data that B cells may have a role in the protection against pneumocystis. Following the review, it was concluded that children on rituximab and an additional immunosuppressant (including corticosteroids) should receive prophylactic cotrimoxazole to cover PCP. Methods Retrospective audit carried out by the team to look at adherence to the new guideline regarding the use of cotrimoxazole for PCP prophylaxis in patients who have had rituximab between August 2017 and May 2019. Results P54 Table 1 Total number of patients who had rituximab 10 Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months) 7 Number of patients on rituximab monotherapy 2 Number of patients who are 6 months post-treatment 1 Number of patients with other risk factors for PCP 1 (hypogammaglobulinaemia) Number of patients who are eligible for prophylaxis, as per the guideline 8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia) Number of patients on cotrimoxazole 7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole We achieved 87.5% compliance in prescribing cotrimoxazole for PCP prophylaxis to all rheumatology patients receiving rituximab alongside another immunosuppressant agent; the one patient who this was not adhered to was due to potential adverse drug pharmacodynamic interaction between cotrimoxazole and methotrexate. Conclusion Although the current evidence points to increased risk of PCP in patients with inherited and iatrogenic defect of T cell function, there is emerging evidence that B cells may have a role too. Hence more work is required to determine the risk of PCP in patients on B cell targeted therapy (BCTT) and the need for prophylaxis. Conflicts of Interest The authors declare no conflicts of interest.

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 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 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.

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