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 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 Outcome and prognostic factors of Pneumocystis jirovecii pneumonia in immunocompromised adults: a prospective observational study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Benjamin Jean Gaborit ◽  
Benoit Tessoulin ◽  
Rose-Anne Lavergne ◽  
Florent Morio ◽  
Christine Sagan ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Sofa Score ◽  
Invasive Mechanical Ventilation ◽  
Solid Organ Transplantation ◽  
Older Age ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Solid Organ ◽  
Pathophysiological Mechanism ◽  
Hypoxemic Acute Respiratory Failure

Abstract Background Pneumocystis jirovecii pneumonia (PJP) remains a severe disease associated with high rates of invasive mechanical ventilation (MV) and mortality. The objectives of this study were to assess early risk factors for severe PJP and 90-day mortality, including the broncho-alveolar lavage fluid cytology profiles at diagnosis. Methods We prospectively enrolled all patients meeting pre-defined diagnostic criteria for PJP admitted at Nantes university hospital, France, from January 2012 to January 2017. Diagnostic criteria for PJP were typical clinical features with microbiological confirmation of P. jirovecii cysts by direct examination or a positive specific quantitative real-time polymerase chain reaction (PCR) assay. Severe PJP was defined as hypoxemic acute respiratory failure requiring high-flow nasal oxygen with at least 50% FiO2, non-invasive ventilation, or MV. Results Of 2446 respiratory samples investigated during the study period, 514 from 430 patients were positive for P. jirovecii. Of these 430 patients, 107 met criteria for PJP and were included in the study, 53 (49.5%) patients had severe PJP, including 30 who required MV. All patients were immunocompromised with haematological malignancy ranking first (n = 37, 35%), followed by solid organ transplantation (n = 27, 25%), HIV-infection (n = 21, 20%), systemic diseases (n = 13, 12%), solid tumors (n = 12, 11%) and primary immunodeficiency (n = 6, 8%). By multivariate analysis, factors independently associated with severity were older age (OR, 3.36; 95% CI 1.4–8.5; p < 0.05), a P. jirovecii microscopy-positive result from bronchoalveolar lavage (BAL) (OR, 1.3; 95% CI 1.54–9.3; p < 0.05); and absence of a BAL fluid alveolitis profile (OR, 3.2; 95% CI 1.27–8.8; p < 0.04). The 90-day mortality rate was 27%, increasing to 50% in the severe PJP group. Factors independently associated with 90-day mortality were worse SOFA score on day 1 (OR, 1.05; 95% CI 1.02–1.09; p < 0.001) whereas alveolitis at BAL was protective (OR, 0.79; 95% CI 0.65–0.96; p < 0.05). In the subgroup of HIV-negative patients, similar findings were obtained, then viral co-infection were independently associated with higher 90-day mortality (OR, 1.25; 95% CI 1.02–1.55; p < 0.05). Conclusions Older age and P. jirovecii oocysts at microscopic examination of BAL were independently associated with severe PJP. Both initial PJP severity as evaluated by the SOFA score and viral co-infection predicted 90-day mortality. Alveolitis at BAL examination was associated with less severe PJP. The pathophysiological mechanism underlying this observation deserves further investigation.

Prophylaxis and treatment of Pneumocystis Jirovecii pneumonia after solid organ transplantation

2018 ◽  
Vol 134 ◽  
pp. 61-67 ◽  
Author(s):  
Susanne Brakemeier ◽  
Anja Pfau ◽  
Bianca Zukunft ◽  
Klemens Budde ◽  
Peter Nickel
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Solid Organ

scholarly journals Is ABO-Incompatible Living Donor Liver Transplantation Really a Good Alternative for Pediatric Recipients?

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 600
Author(s):  
Catherine de Magnée ◽  
Louise Brunée ◽  
Roberto Tambucci ◽  
Aurore Pire ◽  
Isabelle Scheers ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Living Donor ◽  
Living Donor Liver Transplantation ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Humoral Rejection ◽  
Donor Liver ◽  
Retrospective Case ◽  
Donor Liver Transplantation ◽  
Antibody Mediated Rejection

Background: ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been proposed to compensate for donor shortage. To date, few studies have reported detailed ABOi LDLT results in large series of pediatric patients. C4d complement deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in solid organ transplantation. Methods: A retrospective case–control study was conducted, comparing clinical outcomes of each of 34 consecutive pediatric ABOi LDLT recipients with those of 2 non-ABOi pairs (n = 68), matched according to pre-transplant diagnostic criteria, age, and date of transplantation. In addition, we studied the C4d immunostaining pattern in 22 ABOi and in 36 non-ABOi recipients whose liver biopsy was performed within the first 4 post-transplant weeks for suspected acute rejection. Results: The incidence of biliary complications was higher in ABOi recipients (p < 0.05), as were the incidence of acute humoral rejection (p < 0.01) and the incidence of retransplantation (p < 0.05). All children who required retransplantation were older than 1 year at the time of ABOi LDLT. Positive C4d immunostaining was observed in 13/22 (59%) ABOi recipients versus 3/36 (8.3%) non-ABOi recipients (p < 0.0001). Conclusions: ABOi LDLT is a feasible option for pediatric end-stage liver disease but carries increased risks for the recipient, especially for children older than 1 year, even with a specific preparation protocol. C4d immunostaining may be a hallmark of acute humoral rejection in ABOi liver transplantation.

Twice weekly prophylaxis with trimethoprim/sulfamethoxazole for Pneumocystis jirovecii pneumonia in pediatric oncology patients

2020 ◽  
pp. 107815522097904
Author(s):  
Monica Awad ◽  
Caroline M Sierra ◽  
Elhaam Mesghali ◽  
Khaled Bahjri
Keyword(s):  
Pediatric Oncology ◽  
Retrospective Cohort ◽  
Hematologic Malignancies ◽  
Primary Objective ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Weekly Dose ◽  
Single Center ◽  
Oncology Patients ◽  
Prophylaxis Therapy

Current recommendations for prophylaxis of Pneumocystis jirovecii pneumonia in oncology patients include administration of trimethoprim/sulfamethoxazole (TMP/SMX) three times weekly or the same total weekly dose given daily. The primary objective of this study was to evaluate the efficacy of two consecutive days per week of TMP/SMX for prevention of Pneumocystis jirovecii pneumonia (PJP) in pediatric oncology patients. A retrospective cohort, single-center analysis was conducted in oncology patients 21 years and younger who received TMP/SMX for PJP prophylaxis between February 1, 2013 and July 31, 2017. Changes to the prophylaxis regimen were documented and analyzed. A total of 322 patients received TMP/SMX on two consecutive days per week for PJP prevention, of whom four had confirmed PJP (1.3%). Neutropenia was the most common reason for switching to alternative prophylaxis therapy (11.5%). Two consecutive prophylaxis days with TMP/SMX may be insufficient to prevent PJP in children with hematologic malignancies. Neutropenia remains a barrier for TMP/SMX use for PJP prophylaxis. Further studies to compare PJP incidence in children receiving alternative prophylaxis regimens should be considered.

scholarly journals Deferiprone as adjunctive treatment for patients with invasive mucormycosis: A retrospective case series

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Maria N. Chitasombat ◽  
Pimjai Niparuck
Keyword(s):  
Mortality Rate ◽  
Treatment Strategies ◽  
Case Series ◽  
Hematologic Malignancies ◽  
Adjunctive Treatment ◽  
Combination Regimen ◽  
Retrospective Case ◽  
Day Range

Mucormycosis is a life-threatening disease requiring multimodal treatment with antifungals and surgery. The mortality rate remains high, prompting consideration of alternative treatment strategies. Deferiprone has in vitro activity against Mucorales, but its efficacy has never been evaluated in humans. Here, we retrospectively analyzed patients with confirmed mucormycosis who received deferiprone from 2011 to 2017. Five patients had hematologic malignancies and one was diabetic. The sites of infection included sinus-orbit-cerebral (67%), lung (17%), and disseminated infection (17%). Surgery was performed in 83% of cases and achieved local control for 33% of patients. A combination regimen of polyenes plus echinocandins was administered with stepdown treatment using posaconazole. The median duration of antifungal treatment was 86 days (range: 46-435 days) days. Deferiprone was given as adjunctive treatment with a median dose and duration of 100 mg/kd/day (range: 86.2-100 mg/kg/day) and 25 days (range: 15-215 days), respectively. Overall, deferiprone was well-tolerated. Successful outcomes were observed at 12-week follow-up for 67% of patients. The mortality rate at 180- day follow-up was 50%. Adjunctive therapy with deferiprone showed safety and tolerability.

Insights From Practice With Use of Direct Oral Anticoagulants in Transplantation

2018 ◽  
Vol 28 (4) ◽  
pp. 380-385
Author(s):  
Razan Alsheikh ◽  
Osamah M. Alfayez ◽  
Majed S. Al Yami
Keyword(s):  
Case Reports ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Organ Transplant ◽  
Case Series ◽  
Solid Organ ◽  
Special Population ◽  
Retrospective Case ◽  
Transplant Patients ◽  
Attractive Option

Solid organ transplant patients are at risk of developing atrial fibrillation and venous thromboembolism. Direct oral anticoagulants are considered an attractive option for anticoagulation in patients due to their convenience; however, strong evidence of their use in transplantation is lacking. We conducted a search using Pubmed, Embase, and Scopus databases, in addition to International Society of Heart and Lung transplantation and American Transplant Congress abstracts (from 2012 through December 2017). Fourteen articles were reviewed that included case reports, retrospective case series, or chart review analyses of small cohorts. Based on this review, the findings can only generate hypotheses that should be further studied in a larger randomized cohort. This review can help clinicians gain insight into the use of direct oral anticoagulant in this special population. For now, clinicians should be cautious about their use in this special population.

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