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International Journal of Infectious... Sep 2022To investigate the clinical outcomes and risk factors of mortality in patients with rheumatic diseases complicated by Pneumocystis pneumonia (PCP).
OBJECTIVES
To investigate the clinical outcomes and risk factors of mortality in patients with rheumatic diseases complicated by Pneumocystis pneumonia (PCP).
METHODS
Between November 2015 and April 2021, patients with rheumatic diseases with PCP in a tertiary referral hospital were retrospectively enrolled. The diagnosis of PCP requires the fulfillment of clinical, radiographic, and microbiological criteria. Factors associated with in-hospital, 30-day, and 90-day mortality were evaluated.
RESULTS
A total of 128 patients with rheumatic diseases who had a positive quantitative polymerase chain reaction assay for Pneumocystis jirovecii were screened, and 72 patients were included in the final analysis. The median (interquartile range [IQR]) pneumonia severity index (PSI) was 101.5 (77.0-132.0). The median (IQR) adjunctive corticosteroid dosage was 0.6 (0.4-0.9) mg/kg/day prednisolone equivalent. The receiver operating characteristic curve analysis showed that the optimal cutoff point of median adjunctive corticosteroid dosage was 0.6 mg/kg/day to predict in-hospital, 30-day, and 90-day mortality. In the multivariable logistic regression analysis, median adjunctive corticosteroid dosage ≥0.6 mg/kg/day and PSI >90 were independent factors of in-hospital, 30-day, and 90-day mortality.
CONCLUSION
A median adjunctive corticosteroid dosage of ≥0.6 mg/kg/day might be associated with mortality in patients with rheumatic diseases complicated by PCP.
Topics: Adrenal Cortex Hormones; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Rheumatic Diseases
PubMed: 35918031
DOI: 10.1016/j.ijid.2022.07.070 -
Frontiers in Immunology 2023β-glucan is the most abundant polysaccharide in the cell wall of , which has attracted extensive attention because of its unique immunobiological characteristics.... (Review)
Review
β-glucan is the most abundant polysaccharide in the cell wall of , which has attracted extensive attention because of its unique immunobiological characteristics. β-glucan binds to various cell surface receptors, which produces an inflammatory response and accounts for its immune effects. A deeper comprehension of the processes by β-glucan recognizes its receptors, activates related signaling pathways, and regulates immunity as required. Such understanding will provide a basis for developing new therapies against . Herein, we briefly review the structural composition of β-glucans as a vital component of the cell wall, the host immunity mediated by β-glucans after their recognition, and discuss opportunities for the development of new strategies to combat .
Topics: Pneumocystis; beta-Glucans; Glucans; Pneumonia, Pneumocystis; Cell Wall
PubMed: 36845149
DOI: 10.3389/fimmu.2023.1094464 -
Antimicrobial Agents and Chemotherapy Oct 2019
Topics: Caspofungin; Catalytic Domain; Echinocandins; Glucosyltransferases; Humans; Mutagenesis, Site-Directed; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 31548210
DOI: 10.1128/AAC.01296-19 -
JCI Insight Sep 2022Pneumocystis is the most common fungal pulmonary infection in children under the age of 5 years. In children with primary immunodeficiency, Pneumocystis often presents...
Pneumocystis is the most common fungal pulmonary infection in children under the age of 5 years. In children with primary immunodeficiency, Pneumocystis often presents at 3-6 months of age, a time period that coincides with the nadir of maternal IgG and when IgM is the dominant Ig isotype. Because B cells are the dominant antigen-presenting cells for Pneumocystis, we hypothesized the presence of fungal-specific IgMs in humans and mice and that these IgM specificities would predict T cell antigens. We detected fungal-specific IgMs in human and mouse sera and utilized immunoprecipitation to determine whether any antigens were similar across donors. We then assessed T cell responses to these antigens and found anti-Pneumocystis IgM in WT mice, Aicda-/- mice, and in human cord blood. Immunoprecipitation of Pneumocystis murina with human cord blood identified shared antigens among these donors. Using class II MHC binding prediction, we designed peptides with these antigens and identified robust peptide-specific lung T cell responses after P. murina infection. After mice were immunized with 2 of the antigens, adoptive transfer of vaccine-elicited CD4+ T cells showed effector activity, suggesting that these antigens contain protective Pneumocystis epitopes. These data support the notion that germline-encoded IgM B cell receptors are critical in antigen presentation and T cell priming in early Pneumocystis infection.
Topics: Animals; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Germ Cells; Humans; Immunoglobulin M; Lung; Mice; Pneumonia, Pneumocystis
PubMed: 35917185
DOI: 10.1172/jci.insight.161450 -
Infection Dec 2021Pneumocystis jirovecii (P. jirovecii) is increasingly identified on lower respiratory tract specimens of COVID-19 patients. Our narrative review aims to determine... (Review)
Review
BACKGROUND
Pneumocystis jirovecii (P. jirovecii) is increasingly identified on lower respiratory tract specimens of COVID-19 patients. Our narrative review aims to determine whether the diagnosis of pneumocystis jirovecii pneumonia (PJP) in COVID-19 patients represents coinfection or colonization based on the evidence available in the literature. We also discuss the decision to treat COVID-19 patients with coinfection by PJP.
METHODS
A literature search was performed through the Pubmed and Web of Science databases from inception to March 10, 2021.
RESULTS
We identified 12 COVID-19 patients suspected to have PJP coinfection. All patients were critically ill and required mechanical ventilation. Many were immunosuppressed from HIV or long-term corticosteroids and other immunosuppressive agents. In both the HIV and non-HIV groups, severe lymphocytopenia was encountered with absolute lymphocyte and CD4+T cell count less than 900 and 200 cells/mm, respectively. The time to PJP diagnosis from the initial presentation was 7.8 (range 2-21) days. Serum lactate dehydrogenase and beta-D-glucan were elevated in those coinfected with PJP. All patients were treated with anti-PJP therapy, predominantly sulfamethoxazole-trimethoprim with corticosteroids. The overall mortality rate was 41.6%, and comparable for both HIV and non-HIV groups.
CONCLUSION
As the current evidence is restricted to case reports, the true incidence, risk factors, and prognosis of COVID-19 patients with PJP coinfections cannot be accurately determined. Comorbidities of poorly controlled HIV with lymphocytopenia and multiple immunosuppressive therapies are likely predisposing factors for PJP coinfection.
Topics: COVID-19; Coinfection; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; SARS-CoV-2
PubMed: 34059997
DOI: 10.1007/s15010-021-01630-9 -
Journal of Medical Case Reports Feb 2024Pneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus...
INTRODUCTION AND IMPORTANCE
Pneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus (HIV) + patients. We describe a case of PJP pneumonia which provided a diagnostic challenge in a patient who presented with no known risk factors leading to a delay in initiation of appropriate antibiotic therapy.
CASE PRESENTATION
A 71-year-old previously healthy white/Caucasian male presented with subacute hypoxic respiratory failure due to multifocal pneumonia with diffuse bilateral ground glass opacities with consolidations despite prior treatment with antibiotics and steroids. He was admitted and started on intravenous broad-spectrum antibiotics but continued to deteriorate, eventually requiring intubation and transfer to the ICU. Bronchoscopy revealed PJP and treatment was initiated, but the patient developed refractory shock and multiorgan failure, and ultimately died. It was later discovered that he was HIV-1 positive.
CLINICAL DISCUSSION
PJP, as a potential cause of his presentation, was not considered given that our patient lacked any overt risk factors for PJP pneumonia. He continued to worsen despite broad spectrum antibiotic therapy and hence bronchoscopy was pursued. His clinical profile, in hindsight, was suspicious for PJP pneumonia and early PJP-directed antibiotic therapy may have prevented a fatal outcome, as in this case. There was an element of cognitive bias across multiple providers which may have contributed to the delay in treatment despite his rapid clinical decline while on conventional pneumonia treatment protocol. His diagnosis was later evident when his BAL-DFA grew PJP in addition to his low levels of CD4 and CD8 cells. He was found to be HIV-1 positive five days after his death; there was a delay in this diagnosis since all positive HIV tests from the hospital are reported as 'pending' until the presumptive positive sample goes to the Connecticut Department of Public Health State laboratory for the confirmatory test. PJP-targeted therapies were initiated later in our patient's hospital course when the infection had progressed to refractory septic shock with multiorgan failure and eventual death.
CONCLUSION
PJP pneumonia is a fatal disease if not recognized early in the course of illness, and the patient usually undergoes multiple antibiotic regimens before they are diagnosed and receive appropriate clinical care. The gold standard of diagnostic testing for PJP is by obtaining bronchial washings through a flexible bronchoscopy and the turnaround time for such results may take a few days to result. A significant proportion of patients may not have any overt risk factors of immunosuppression and early empiric treatment for PJP may be clinically appropriate as the delay in diagnosis may be associated with significant morbidity and mortality risk.
Topics: Humans; Male; Aged; Pneumonia, Pneumocystis; Pneumocystis carinii; Risk Factors; Anti-Bacterial Agents; HIV Infections
PubMed: 38342895
DOI: 10.1186/s13256-024-04350-4 -
Frontiers in Public Health 2021We performed a meta-analysis to systematically review the risk factors of mortality from non-HIV-related pneumonia (PcP) and provide the theoretical basis for managing... (Meta-Analysis)
Meta-Analysis
We performed a meta-analysis to systematically review the risk factors of mortality from non-HIV-related pneumonia (PcP) and provide the theoretical basis for managing non-HIV-related PcP. PubMed, Embase, Web of Science, the Cochrane Library and CNKI databases were searched. A meta-analysis of the risk factors of mortality from non-HIV-related PcP was conducted. A total of 19 studies and 1,310 subjects were retrieved and included in the meta-analysis, including 485 and 825 patients in the non-survivor and survivor groups, respectively. In the primary analysis, age, concomitant with other pulmonary diseases at diagnosis of PcP, solid tumors, cytomegalovirus(CMV) co-infection, lactate dehydrogenase (LDH), lymphocyte count, invasive ventilation during hospitalization, and pneumothorax were associated with mortality from non-HIV-related PcP, whereas sex, albumin, PcP prophylaxis, use of corticosteroids after admission, and time from onset of symptoms to treatment were not associated with mortality from non-HIV-related PcP. The mortality rate of non-HIV-infected patients with PcP was still high. Age, concomitant with other pulmonary diseases at diagnosis of PcP, solid tumors, CMV co-infection, LDH, lymphocyte count, invasive ventilation during hospitalization, and pneumothorax were risk factors of mortality from non-HIV-related PcP. Improved knowledge of prognostic factors is crucial to guide early treatment.
Topics: Coinfection; Cytomegalovirus Infections; Humans; Pneumocystis; Pneumonia, Pneumocystis; Risk Factors
PubMed: 34222179
DOI: 10.3389/fpubh.2021.680108 -
MSphere Sep 2019pneumonia is the most common serious opportunistic infection in patients with HIV/AIDS. Furthermore, pneumonia is a feared complication of the immunosuppressive drug...
pneumonia is the most common serious opportunistic infection in patients with HIV/AIDS. Furthermore, pneumonia is a feared complication of the immunosuppressive drug regimens used to treat autoimmunity, malignancy, and posttransplantation rejection. With an increasing at-risk population, there is a strong need for novel approaches to discover diagnostic and vaccine targets. There are multiple challenges to finding these targets, however. First, has a largely unannotated genome. To address this, we evaluated each protein encoded within the genome by comparisons to proteins encoded within the genomes of other fungi using NCBI BLAST. Second, relies on a multiphasic life cycle, as both the transmissible form (the ascus) and the replicative form (the trophozoite [troph]) reside within the alveolar space of the host. To that end, we purified asci and trophs from and utilized transcriptomics to identify differentially regulated genes. Two such genes, and , are differentially regulated in the ascus and the troph, respectively, and can be utilized to characterize the state of the life cycle , encoding a β-1,3-glucan synthase with a large extracellular domain previously identified using surface proteomics, was more highly expressed on the ascus form of GSC-1 ectodomain immunization generated a strong antibody response that demonstrated the ability to recognize the surface of the asci. GSC-1 ectodomain immunization was also capable of reducing ascus burden following primary challenge with Finally, mice immunized with the GSC-1 ectodomain had limited fungal burden following natural transmission of using a cohousing model. The current report enhances our understanding of biology in a number of ways. First, the current study provided a preliminary annotation of the genome, addressing a long-standing issue in the field. Second, this study validated two novel transcripts enriched in the two predominant life forms of These findings allow better characterization of the life cycle and could be valuable diagnostic tools. Furthermore, this study outlined a novel pipeline of -omics techniques capable of revealing novel antigens (e.g., GSC-1) for the development of vaccines against .
Topics: Animals; Antigens, Fungal; Female; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Genome, Fungal; Lung; Mice; Mice, Inbred C57BL; Pneumocystis; Pneumonia, Pneumocystis; Proteomics; Transcriptome
PubMed: 31484742
DOI: 10.1128/mSphere.00488-19 -
Antimicrobial Agents and Chemotherapy Feb 2021Antifungal prophylaxis is recommended to prevent invasive fungal disease caused by spp., spp., and in patients at risk for opportunistic infections, such as...
Antifungal prophylaxis is recommended to prevent invasive fungal disease caused by spp., spp., and in patients at risk for opportunistic infections, such as allogeneic blood or marrow transplant recipients, patients with hematological disease undergoing chemotherapy, or patients on immunosuppressive therapies. Current approaches to antifungal prophylaxis require multiple agents to cover these key fungi. Rezafungin, a novel echinocandin designed for next-generation properties (e.g., greater stability and long-acting pharmacokinetics for once-weekly dosing), has demonstrated activity against and spp. and efficacy against spp. biofilms. Rezafungin was evaluated in studies of prophylactic efficacy using immunosuppressed mouse models of invasive candidiasis, aspergillosis, and pneumonia. Rezafungin reduction of CFU burden was generally greater with increasing drug concentrations (5, 10, or 20 mg/kg) and when rezafungin was administered closer to the time of fungal challenge (day -1, -3, or -5). Similarly, in the aspergillosis model, survival rates increased with drug concentrations and when rezafungin was administered closer to the time of fungal challenge. Against , rezafungin significantly reduced trophic nuclei and asci counts at all doses tested. Rezafungin prevented infection at the two higher doses compared to vehicle and had comparable activity to the active control trimethoprim-sulfamethoxazole at human equivalent doses for prevention. These findings support phase 3 development of rezafungin and the potential for single-agent prophylaxis against invasive fungal disease caused by spp., spp., and .
Topics: Antifungal Agents; Aspergillosis; Candidiasis, Invasive; Echinocandins; Humans; Mice; Microbial Sensitivity Tests; Pneumonia, Pneumocystis; Animals
PubMed: 33318018
DOI: 10.1128/AAC.01992-20 -
Mycopathologia May 2024To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number...
OBJECTIVES
To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia.
METHODS
We examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics.
RESULTS
Among 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-β-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved.
CONCLUSION
Detection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia.
Topics: Humans; Pneumonia, Pneumocystis; Male; High-Throughput Nucleotide Sequencing; Pneumocystis carinii; Female; Middle Aged; Aged; Adult; Aged, 80 and over; Respiratory System; Young Adult; Molecular Diagnostic Techniques
PubMed: 38704795
DOI: 10.1007/s11046-024-00849-y