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International Journal of Infectious... Jun 2023The risk factors for late-onset Pneumocystis jirovecii pneumonia (PCP) after liver transplantation (LT) have not been well studied. We aimed to analyze the clinical...
OBJECTIVES
The risk factors for late-onset Pneumocystis jirovecii pneumonia (PCP) after liver transplantation (LT) have not been well studied. We aimed to analyze the clinical features preceding PCP in LT recipients that would guide individualized prophylaxis.
METHODS
Among 742 patients who underwent LT and routine PCP prophylaxis from January 2009 through December 2019 at Severance Hospital, 27 patients developed PCP. We conducted a retrospective case-control study matching each patient with four controls and analyzed the risk factors for late-onset PCP.
RESULTS
After 6 months, post-transplant PCP cases increased steadily with an overall incidence of 6.36 cases per 1000 patient-year. The PCP-related mortality was 37.0%. In the multivariate analyses, age at LT ≥65 years (odds ratio [OR], 13.305; 95% confidence interval [CI], 2.507-70.618; P = 0.002), cytomegalovirus infection (OR, 5.390; 95% CI, 1.602-18.132; P = 0.006), steroid pulse therapy (OR, 6.564; 95% CI, 1.984-21.719; P = 0.002), hepatocellular carcinoma recurrence (OR, 18.180; 95% CI, 3.420-96.636; P = 0.001), and lymphocytopenia (OR, 3.758; 95% CI, 1.176-12.013; P = 0.026) were independently associated with PCP.
CONCLUSION
Late-onset PCP after routine prophylaxis after LT remains a lethal infection and is associated with age ≥65 years at LT, cytomegalovirus infection, steroid pulse therapy, hepatocellular carcinoma recurrence, and lymphocytopenia. Targeted prophylaxis considering these risk factors could improve the prevention of this potentially lethal complication.
Topics: Humans; Aged; Pneumonia, Pneumocystis; Retrospective Studies; Case-Control Studies; Pneumocystis carinii; Liver Transplantation; Carcinoma, Hepatocellular; Risk Factors; Cytomegalovirus Infections; Transplant Recipients; Liver Neoplasms; Lymphopenia; Steroids
PubMed: 37044172
DOI: 10.1016/j.ijid.2023.04.387 -
Journal of Infection and Public Health Jun 2023Pneumocystis jirovecii is an opportunistic fungus recognized for causing P. jirovecii pneumonia. The global prevalence is thought to be higher than 400,000 annual cases,...
BACKGROUND
Pneumocystis jirovecii is an opportunistic fungus recognized for causing P. jirovecii pneumonia. The global prevalence is thought to be higher than 400,000 annual cases, although detailed information about epidemiological patterns is scarce.
METHODOLOGY
A retrospective longitudinal descriptive study was performed among patients with diagnosis of pneumocystosis according to Classification of Diseases 9th edition, Clinical Modification (code 136.3 for the cases from 1997 to 2015; and 10th edition code B59.0 for cases from 2016 to 2020 in Spanish public hospitals from 1 January 1997-31 December 2020.
RESULTS
A total of 25289 cases were diagnosed. The period incidence rate was 2.36 (95 % CI, 2.33-2.39) cases per 100,000 person-years. Infection was more frequent among men (72.2 %) than among women (27.8 %). Comorbidity was the main characteristic of this cohort. Up to 72.3 % of pneumocystis-infected patients (18293) had HIV coinfection. During the study period, there was a progressive decrease in the number of HIV coinfected cases as the group of patients without HIV infection increased, with the largest group in 2017. The lethality rate in the cohort was 16.7 %. The global cost was €229,234,805 and the average ( ± SD) cost per patient was €9065 ( ± 9315).
CONCLUSIONS
The epidemiology of pneumocystosis in Spain has changed in the last two decades. We noted in our study the possibility of a reemergence among non-HIV immunocompromised patients as patients with hematological and nonhematological neoplasia and other risk groups. The lethality of pneumocystosis continues to be high, and the underlying diseases are the main variable associated with lethality.
Topics: Male; Humans; Female; Pneumonia, Pneumocystis; HIV Infections; Retrospective Studies; Pneumocystis carinii; Immunocompromised Host
PubMed: 37030036
DOI: 10.1016/j.jiph.2023.03.022 -
Medicine Apr 2023Severe Pneumocystis pneumonia (PCP) has a poor prognosis, and its early and precise diagnosis is difficult in immunocompromised individuals. Therefore, this study...
Severe Pneumocystis pneumonia (PCP) has a poor prognosis, and its early and precise diagnosis is difficult in immunocompromised individuals. Therefore, this study explored the diagnostic value of metagenomic next-generation sequencing (mNGS) of peripheral blood in diagnosing severe PCP in patients with hematological diseases. This prospective study analyzed the clinical manifestations, mNGS results (from the peripheral blood), traditional pathogen detection results, laboratory test results, chest computed tomography (CT) images, treatments, and outcomes of severe PCP in hematological patients who were hospitalized in the 2 centers of the Affiliated Hospital of Soochow University between September 2019 and October 2021. A total of 31 cases of hematological diseases complicated with pulmonary infections, including 7 cases of severe PCP diagnosed by mNGS performed on peripheral blood samples, were analyzed. Traditional pathogen detection methods for PCP cannot be used. In contrast, the laboratory readings for Pneumocystis jirovecii (Pj) detected within 48 hours of symptom onset by mNGS on the 7 blood samples ranged from 12 to 5873, with a median value of 43. Under the guidance of the mNGS results, preemptive antimicrobial therapy with trimethoprim/sulfamethoxazole alone or in combination with caspofungin was administered to treat Pj. After treatment, 4 patients recovered, and 3 patients died of acute respiratory failure and acute respiratory distress syndrome (ARDS). MNGS performed on peripheral blood samples is optional but can provide early recognition of severe PCP and help guide empirical treatment in critical hematological patients.
Topics: Humans; Pneumonia, Pneumocystis; Prospective Studies; High-Throughput Nucleotide Sequencing; Caspofungin; Death; Pneumocystis carinii; Respiratory Distress Syndrome
PubMed: 37026960
DOI: 10.1097/MD.0000000000033399 -
Frontiers in Cellular and Infection... 2023(PJ) is an opportunistic pathogenic fungus, and PJ pneumonia (PJP) is a commonly problem in HIV-positive patients. While PJP is not caused by HIV, it generally advances...
BACKGROUND
(PJ) is an opportunistic pathogenic fungus, and PJ pneumonia (PJP) is a commonly problem in HIV-positive patients. While PJP is not caused by HIV, it generally advances rapidly and can quickly lead to severe respiratory failure. To improve pediatricians' understanding of the condition and aid early accurate diagnoses and therapy, we examined the clinical characteristics of five instances of non-HIV related PJP (NH-PJP) in children and the efficacy of metagenomic next-generation sequencing (mNGS) in its diagnosis.
METHODS
From January 2020 to June 2022, five children with NH-PJP were admitted to the PICU of the First Affiliated Hospital of Zhengzhou University. We retrospectively summarize the clinical presentation, previous histories, routine laboratory findings, treatment, outcome of regression, and results of mNGS in these five children.
RESULTS
Five male children between the ages of 11 months and 14 years had an acute onset on NH-PJP, three of the children had chest tightness after activity, shortness of breath and paroxysmal dry cough, - and two had high fever and dry cough. All five of the children had several flocculent high-density pictures in both lungs at the beginning of the disease, and lung auscultation revealed coarse breath sounds in both lungs, one of which was accompanied by a modest quantity of dry rales. PJ nuclear sequences were found in one patient and four patients' blood and alveolar lavage fluid. All five children were treated with Trimethoprim-sulfamethoxazole (TMP-SMX) in combination with Caspofungin and corresponding symptomatic treatment. Four patients were cured and one patient died.
CONCLUSION
Children commonly encounter an initial exposure to NH-PJP, which manifests as a high fever, dry cough, chest discomfort, dyspnea that worsens over time, fast disease progression, and a high death rate. The clinical presentation of children with PJ infection should be taken into consideration along with the results for diagnose. mNGS has higher sensitivity and a shorter detection period compared to identification of PJP.
Topics: Humans; Male; Child; Infant; Pneumonia, Pneumocystis; Retrospective Studies; Cough; Pneumocystis carinii; High-Throughput Nucleotide Sequencing
PubMed: 37009508
DOI: 10.3389/fcimb.2023.1132472 -
Internal Medicine (Tokyo, Japan) Nov 2023Pneumocystis pneumonia (PCP) is an opportunistic infection that presents a ground-glass appearance in the lungs on chest radiography. Interstitial lung disease is a...
Pneumocystis pneumonia (PCP) is an opportunistic infection that presents a ground-glass appearance in the lungs on chest radiography. Interstitial lung disease is a commonly reported adverse effect of immune checkpoint inhibitor (ICI) treatment; however, there are few reports of ICI treatment-associated PCP infection. A 77-year-old man with lung adenocarcinoma was administered pembrolizumab and hospitalized for dyspnea 2 weeks after treatment. Chest computed tomography showed bilateral ground-glass opacities in all lung lobes. PCP was therefore diagnosed, and steroids and sulfamethoxazole-trimethoprim were initiated. Following treatment, the patient's condition improved promptly. This report suggests that ICI treatment can cause PCP infection.
Topics: Male; Humans; Aged; Pneumonia, Pneumocystis; Pneumocystis carinii; Adenocarcinoma of Lung; Lung Neoplasms
PubMed: 37005268
DOI: 10.2169/internalmedicine.1163-22 -
BMC Infectious Diseases Mar 2023Pneumocystis jirovecii infection is the most common opportunistic infection that causes pneumonia in human immunodeficiency virus (HIV)-infected patients; however,... (Review)
Review
BACKGROUND
Pneumocystis jirovecii infection is the most common opportunistic infection that causes pneumonia in human immunodeficiency virus (HIV)-infected patients; however, extrapulmonary P. jirovecii infection is extremely rare after the use of antiretroviral therapy. Here, we present the second reported case of paraspinal mass caused by P. jirovecii infection in an advanced HIV-infected patient.
CASE PRESENTATION
A 45-year-old woman presented with dyspnea on exertion, and significant weight loss within the preceding 4 months. Initial complete blood count (CBC) findings revealed pancytopenia with a hemoglobin (Hb) level of 8.9 g/dL, a white blood cell (WBC) count of 2180 cells/mm with 68% neutrophils, and a platelet count of 106,000 cells/mm. Anti-HIV was positive with an absolute cluster of differentiation 4 (CD4) count of 16 cells/ mm. A computed tomography scan of the chest revealed an enhancing soft tissue mass-like lesion at the right paravertebral region (T5-T10 level) and a thick-walled cavity lesion at the left lower lung. A CT-guided biopsy of the paravertebral mass was performed and histopathology revealed granulomatous inflammation consisting of dense aggregates of epithelioid cells and macrophages, and scattered foci of pink foamy to granular materials amidst the granulomatous inflammation. Gomori methenamine silver (GMS) staining revealed thin cystic-like structures (ascus) that were observed to be morphologically consistent with P. jirovecii. Molecular identification and DNA sequencing from the paraspinal mass was 100% identical to P. Jirovecii. The patient was successfully treated with oral trimethoprim-sulfamethoxazole for 3 weeks and antiretroviral therapy (ART) with tenofovir (TDF), lamivudine (3TC), and dolutegravir (DTG). A follow-up CT scan of the chest at 2 months after treatment showed a decrease in sizes of both the paravertebral mass and the cavitary lung lesion.
CONCLUSIONS
Extrapulmonary pneumocystosis (EPCP) has become an extremely rare condition in HIV-infected patients after the widespread use of ART. EPCP should be considered in ART-naive HIV-infected patients suspected of having or diagnosed with Pneumocystis jirovecii pneumonia who present with atypical symptoms and/or signs. Histopathologic examination with GMS staining of affected tissue is necessary for the diagnosis of EPCP.
Topics: Female; Humans; Middle Aged; Pneumocystis carinii; HIV; Pneumonia, Pneumocystis; HIV Infections; Lamivudine; Inflammation
PubMed: 36991362
DOI: 10.1186/s12879-023-08143-w -
BMJ Open Mar 2023Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone, once every 3 weeks (R-CHOP21) is commonly used in non-Hodgkin's lymphoma (NHL), but accompanied... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone, once every 3 weeks (R-CHOP21) is commonly used in non-Hodgkin's lymphoma (NHL), but accompanied by pneumonia (PCP) as a fatal treatment complication. This study aims to estimate the specific effectiveness and cost-effectiveness of PCP prophylaxis in NHL undergoing R-CHOP21.
DESIGN
A two-part decision analytical model was developed. Prevention effects were determined by systemic review of PubMed, Embase, Cochrane Library and Web of Science from inception to December 2022. Studies reporting results of PCP prophylaxis were included. Enrolled studies were quality assessed with Newcastle-Ottawa Scale. Costs were derived from the Chinese official websites, and clinical outcomes and utilities were obtained from published literature. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses (DSA and PSA). Willingness-to-pay (WTP) threshold was set as US$31 315.23/quality-adjusted life year (QALY) (threefold the 2021 per capita Chinese gross domestic product).
SETTING
Chinese healthcare system perspective.
PARTICIPANTS
NHL receiving R-CHOP21.
INTERVENTIONS
PCP prophylaxis versus no prophylaxis.
MAIN OUTCOME MEASURES
Prevention effects were pooled as relative risk (RR) with 95% CI. QALYs and incremental cost-effectiveness ratio (ICER) were calculated.
RESULTS
A total of four retrospective cohort studies with 1796 participants were included. PCP risk was inversely associated with prophylaxis in NHL receiving R-CHOP21 (RR 0.17; 95% CI 0.04 to 0.67; p=0.01). Compared with no prophylaxis, PCP prophylaxis would incur an additional cost of US$527.61, and 0.57 QALYs gained, which yielded an ICER of US$929.25/QALY. DSA indicated that model results were most sensitive to the risk of PCP and preventive effectiveness. In PSA, the probability that prophylaxis was cost-effective at the WTP threshold was 100%.
CONCLUSION
Prophylaxis for PCP in NHL receiving R-CHOP21 is highly effective from retrospective studies, and routine chemoprophylaxis against PCP is overwhelmingly cost-effective from Chinese healthcare system perspective. Large sample size and prospective controlled studies are warranted.
Topics: Male; Humans; Cost-Effectiveness Analysis; Retrospective Studies; Pneumonia, Pneumocystis; Prospective Studies; Prostate-Specific Antigen; Cost-Benefit Analysis; Lymphoma, Non-Hodgkin; Quality-Adjusted Life Years
PubMed: 36972963
DOI: 10.1136/bmjopen-2022-068943 -
Avicenna Journal of Medicine Jan 2023pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has... (Review)
Review
pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has been a decline in pneumonia incidence in HIV since the introduction of antiretroviral medications. However, its incidence is increasing in non-HIV immunocompromised patients including those with solid organ transplantation, hematopoietic stem cell transplantation, solid organ tumors, autoimmune deficiencies, and primary immunodeficiency disorders. We aim to review and summarize the etiology, epidemiology, clinical presentation, diagnosis, and management of pneumonia in HIV, and non-HIV patients. HIV patients usually have mild-to-severe symptoms, while non-HIV patients present with a rapidly progressing disease. Induced sputum or bronchoalveolar lavage fluid can be used to make a definitive diagnosis of pneumonia. Trimethoprim-sulfamethoxazole is considered to be the first-line drug for treatment and has proven to be highly effective for pneumonia prophylaxis in both HIV and non-HIV patients. Pentamidine, atovaquone, clindamycin, and primaquine are used as second-line agents. While several diagnostic tests, treatments, and prophylactic regimes are available at our disposal, there is need for more research to prevent and manage this disease more effectively.
PubMed: 36969352
DOI: 10.1055/s-0043-1764375 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Feb 2023To summarize the original CT features of Pneumocystis Jirovecii pneumonia in patients with hematological diseases. A retrospective analysis was carried out in 46...
To summarize the original CT features of Pneumocystis Jirovecii pneumonia in patients with hematological diseases. A retrospective analysis was carried out in 46 patients with proven pneumocystis pneumonia (PJP) in the Hospital of Hematology, Chinese Academy of Medical Sciences between January 2014 and December 2021. All patients had multiple chests CT and related laboratory examinations, imaging typing were conducted based on the initial CT presentation, and the distinct imaging types were analyzed against the clinical data. In the analysis, there were 46 patients with proven pathogenesis, 33 males, and 13 females, with a median age of 37.5 (2-65) years. The diagnosis was validated by bronchoalveolar lavage fluid (BALF) hexamine silver staining in 11 patients and clinically diagnosed in 35 cases. Of the 35 clinically diagnosed patients, 16 were diagnosed by alveolar lavage fluid macrogenomic sequencing (BALF-mNGS) and 19 by peripheral blood macrogenomic sequencing (PB-mNGS) . The initial chest CT presentation was categorized into 4 types, including ground glass (GGO) type in 25 cases (56.5%) , nodular type in 10 cases (21.7%) , fibrosis type in 4 cases (8.7%) , and mixed type in 5 cases (13.0%) . There was no substantial discrepancy in CT types among confirmed patients, BALF-mNGS diagnosed patients and PB-mNGS diagnosed patients ((2)=11.039, =0.087) . The CT manifestations of confirmed patients and PB-mNGS diagnosed patients were primarily GGO type (67.6%, 73.7%) , while that of BALF-mNGS diagnosed patients were nodular type (37.5%) . Of the 46 patients, 63.0% (29/46) had lymphocytopenia in the peripheral blood, 25.6% (10/39) with positive serum G test, and 77.1% (27/35) with elevated serum lactate dehydrogenase (LDH) . There were no great discrepancies in the rates of lymphopenia in peripheral blood, positive G-test, and increased LDH among different CT types (all >0.05) . The initial chest CT findings of PJP in patients with hematological diseases were relatively prevalent with multiple GGO in both lungs. Nodular and fibrosis types were also the initial imaging findings for PJP.
Topics: Male; Female; Humans; Adult; Middle Aged; Aged; Pneumonia, Pneumocystis; Retrospective Studies; Pneumocystis carinii; Hematologic Diseases; Tomography, X-Ray Computed; Fibrosis
PubMed: 36948865
DOI: 10.3760/cma.j.issn.0253-2727.2023.02.006 -
Therapeutic Advances in Infectious... 2023HIV-negative patients have substantial mortality from pneumonia (PJP). We lack predictors of HIV-negative PJP-associated mortality.
Previous corticosteroid exposure associates with an increased pneumonia mortality among HIV-negative patients: a global research network with a follow-up multicenter case-control study.
BACKGROUND
HIV-negative patients have substantial mortality from pneumonia (PJP). We lack predictors of HIV-negative PJP-associated mortality.
OBJECTIVE
We aim to characterize the role of prior corticosteroid exposure in PJP-related mortality.
METHODS
We queried a global research network to identify adult HIV-negative patients with PJP with or without corticosteroid exposure in the preceding year before diagnosis ( = 8,021). We performed a propensity score-matched analysis to adjust baseline patient characteristics and analyzed outcomes. We follow-up the results with a multicenter ten years retrospective case-control cohort of HIV-negative patients tested for PJP by PCP Direct Fluorescent Antigen. We used a Cox proportional hazards model for survival analysis.
RESULTS
1822 HIV-negative propensity-scored matched patients with prior corticosteroid exposure had significantly increased 10 weeks (16% 9%, p < 0.0001) and one-year mortality after PJP diagnosis (23% 14%, < 0.0001). (1→3)-β-D-glucan (197.6 ± 155.8 63 ± 0 pg/ml, = 0.014), ferritin levels (1227 ± 2486 768 ± 1060 mcg/l, = 0.047), lymphopenia (1.5 ± 1.5 2.0 ± 1.6 10 cells/µl, < 0.0001) and hypoxia (SatO: 86.7% 91.6%, < 0.0001) were higher or worse in those with prior steroid use. Patients who died were more likely to have previously received dexamethasone (35% 16%, < 0.001) or prednisone (49% 29%, < 0.001). Adjusted Cox proportional-hazard model validation showed an independently increased mortality at 10 weeks (HR: 3.7, CI: 1.5-9.2, = 0.004) and 1 year (HR: 4.5, CI: 2.0-10.4, < 0.0001) among HIV-negative patients with previous corticosteroid exposure.
CONCLUSION
Preceding corticosteroids in HIV-negative patients with PJP are associated with higher mortality. A higher fungal burden may influence corticosteroid-mediated mortality. Assessment of PJP prophylaxis must become a standard clinical best practice when instituting corticosteroid therapy courses.
PubMed: 36938147
DOI: 10.1177/20499361231159481