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Medicine Feb 2023Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human... (Review)
Review
RATIONALE
Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human immunodeficiency virus (HIV) infection, organ transplantation, leukemia, and immunosuppressive therapy. Here we describe the rare case of PCP in a non-HIV-infected diabetic patient and find possible reasons for the association through a literature review.
PATIENT CONCERNS
A 65-years-old male was admitted to our hospital due to a 10-year history of abnormal blood glucose levels and edema of both lower extremities for half a month. However, the patient developed a high fever and progressive dyspnea during hospitalization.
DIAGNOSES
The patient had elevated blood sugar levels, a low white blood cell count within normal limits, and severe lymphopenia. His blood G test and lactate dehydrogenase levels increased significantly. Multiple sputa and bronchoalveolar lavage fluid specimens for Pneumocystis jirovecii (PJ) nucleic acid detection were positive. Chest computed tomography scan demonstrated hazy patchy shadows in the lungs suspected to be pulmonary infections. No tumor, transplantation, or an autoimmune disease was found in the examinations. The patient was diagnosed with PCP finally.
INTERVENTIONS
A combination of oral trimethoprim-sulfamethoxazole and intravenous caspofungin was administered immediately against PJ. The patient was also treated with noninvasive ventilator-assisted ventilation, subcutaneous insulin, and hemodialysis therapy.
OUTCOMES
The patient was discharged home finally with a fair general condition and was followed up without respiratory symptoms.
LESSONS
The compromised immunity in HIV-negative patients with diabetes may be related to lymphocyte decrease and dysfunction, which may cause diabetic patients prone to PJ. Although PCP is rare in diabetes, it should be paid attention to the high rate of misdiagnosis and missed diagnosis.
Topics: Humans; Male; Aged; Pneumonia, Pneumocystis; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; HIV Infections; Diabetes Mellitus
PubMed: 36749248
DOI: 10.1097/MD.0000000000032290 -
MSphere May 2021Prior work has shown that parenterally administered anti-CD20 (5D2) inhibits CD4 T cell priming in response to challenge with and predisposes to pneumonia. In this...
Prior work has shown that parenterally administered anti-CD20 (5D2) inhibits CD4 T cell priming in response to challenge with and predisposes to pneumonia. In this study, we investigated the effect of subcutaneous anti-CD20 antibody and infection. In mice with primary infection, anti-CD20 antibody treatment depleted both CD19 and CD27 CD19 cells but not T cells in the lung at days 14 and 28 after inoculation. Although anti-CD20 antibody treatment impaired fungal clearance at day 14 postinfection, fungal burden in the lungs was substantially reduced at day 28 in both depleted and control mice in the low-dose group. Subcutaneous anti-CD20 antibody treatment did not alter antigen-specific serum immunoglobulin levels in mice compared with control mice, and there were no significant differences in the numbers of lung gamma interferon-positive (IFN-γ) CD4, interleukin 4-positive (IL-4) CD4, IL-5 CD4, and IL-17A CD4 cells between depleted and control mice after infection. In mice with secondary infection, the lung fungal burden was comparable between depleted and control mice 14 days after reinfection. Low-dose subcutaneous anti-CD20 antibody treatment may delay fungal clearance, but it did not impair the ability of the host to clear infection, irrespective of primary or secondary infection. Anti-CD20 antibody therapy is used for both cancer and autoimmune disease but has been shown to be associated with pneumonia in humans. This study shows that low-dose subcutaneous anti-CD20 can modulate B cell populations without grossly perturbing fungal immunity against lung infection.
Topics: Animals; Antibodies, Monoclonal; Antigens, CD20; B-Lymphocytes; Injections, Subcutaneous; Lung; Lymphocyte Depletion; Mice; Mice, Inbred C57BL; Pneumocystis; Pneumonia, Pneumocystis
PubMed: 33952667
DOI: 10.1128/mSphere.01144-20 -
Journal of Immunology (Baltimore, Md. :... Jul 2015Pneumocystis pneumonia remains a common opportunistic infection in the diverse immunosuppressed population. One clear risk factor for susceptibility to Pneumocystis is a...
Pneumocystis pneumonia remains a common opportunistic infection in the diverse immunosuppressed population. One clear risk factor for susceptibility to Pneumocystis is a declining CD4(+) T cell count in the setting of HIV/AIDS or primary immunodeficiency. Non-HIV-infected individuals taking immunosuppressive drug regimens targeting T cell activation are also susceptible. Given the crucial role of CD4(+) T cells in host defense against Pneumocystis, we used RNA sequencing of whole lung early in infection in wild-type and CD4-depleted animals as an unbiased approach to examine mechanisms of fungal clearance. In wild-type mice, a strong eosinophil signature was observed at day 14 post Pneumocystis challenge, and eosinophils were increased in the bronchoalveolar lavage fluid of wild-type mice. Furthermore, eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice were more susceptible to Pneumocystis infection when compared with BALB/c controls, and bone marrow-derived eosinophils had in vitro Pneumocystis killing activity. To drive eosinophilia in vivo, Rag1(-/-) mice were treated with a plasmid expressing IL-5 (pIL5) or an empty plasmid control via hydrodynamic injection. The pIL5-treated mice had increased serum IL-5 and eosinophilia in the lung, as well as reduced Pneumocystis burden, compared with mice treated with control plasmid. In addition, pIL5 treatment could induce eosinophilia and reduce Pneumocystis burden in CD4-depleted C57BL/6 and BALB/c mice, but not eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice. Taken together, these results demonstrate that an early role of CD4(+) T cells is to recruit eosinophils to the lung and that eosinophils are a novel candidate for future therapeutic development in the treatment of Pneumocystis pneumonia in the immunosuppressed population.
Topics: Animals; Bronchoalveolar Lavage Fluid; CD4-Positive T-Lymphocytes; Eosinophils; Female; GATA1 Transcription Factor; Gene Expression; Genetic Therapy; Homeodomain Proteins; Host-Pathogen Interactions; Interleukin-5; Leukocyte Count; Lung; Lymphocyte Activation; Lymphocyte Depletion; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Plasmids; Pneumocystis; Pneumonia, Pneumocystis; Time Factors
PubMed: 25994969
DOI: 10.4049/jimmunol.1403162 -
Journal de Mycologie Medicale Mar 2023To analyze clinical characteristics and risk factors for in-hospital mortality in patients coinfected with P. jirovecii and Aspergillus.
OBJECTIVE
To analyze clinical characteristics and risk factors for in-hospital mortality in patients coinfected with P. jirovecii and Aspergillus.
METHODS
This study included 53 patients with coinfection of P. jirovecii pneumonia (PJP) and invasive pulmonary aspergillosis (IPA) in our center from January 2011 to December 2021. All cases were divided into survivor (n=27) and non-survivor groups (n=26). Medical records, laboratory and radiology data were collected. Risk factors for in-hospital mortality were identified by multivariable analyses.
RESULTS
HIV-positive patients accounted for 3.8%. Fever (77.4%), dyspnea (69.8%) and wet cough (24.5%) were common symptoms. Ground-glass opacity (83.0%), consolidation (71.7%), septal thickening (66.0%), and nodules (54.7%) were the most common radiological signs. CD4+ T cell count and serum albumin (ALB) level were significantly lower in non-survival group than in the survival group. Conversely, serum lactate dehydrogenase (LDH) and procalcitonin (PCT) levels were higher in non-survival group than in survival group. Lactic acidosis [odds ratio (OR): 33.999,95% confidential interval (CI): 3.112-371.409; p=0.004], low CD4+ T cell count (<114 cell/µL) [OR: 19.343, 95% CI: 1.533-259.380; p=0.022] and high level of LDH (> 519 U/L) [OR: 11.422, 95% CI: 1.271-102.669; p=0.030] were independent risk factors for mortality.
CONCLUSION
PJP coinfected with IPA incurs high mortality with nonspecific clinical characteristics and is more likely to involve HIV-negative patients. Lactic acidosis, low CD4+ T cell count and high LDH level are independent risk factors for mortality, close monitoring of these parameters is necessary to help distinguish high-risk patients and make appropriate clinical decisions.
Topics: Humans; Pneumocystis carinii; Coinfection; Hospital Mortality; Acidosis, Lactic; HIV Infections; Risk Factors; Pneumonia, Pneumocystis; Aspergillus; Invasive Pulmonary Aspergillosis; Retrospective Studies
PubMed: 36265259
DOI: 10.1016/j.mycmed.2022.101330 -
American Journal of Hematology Nov 2017
Topics: Adenine; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Piperidines; Pneumocystis carinii; Pneumonia, Pneumocystis; Pyrazoles; Pyrimidines
PubMed: 28815693
DOI: 10.1002/ajh.24890 -
Microbiology Spectrum Sep 2021Pneumocystis jirovecii is a threat to iatrogenically immunosuppressed individuals, a heterogeneous population at rapid growth. We assessed the ability of an in-house...
Pneumocystis jirovecii is a threat to iatrogenically immunosuppressed individuals, a heterogeneous population at rapid growth. We assessed the ability of an in-house semiquantitative real-time PCR assay to discriminate Pneumocystis pneumonia (PCP) from colonization and identified risk factors for infection in these patients. Retrospectively, 242 PCR-positive patients were compared according to PCP status, including strata by immunosuppressive conditions, human immunodeficiency virus (HIV) infection excluded. Associations between host characteristics and cycle threshold () values, semiquantitative real-time PCR correlates of fungal loads in lower respiratory tract specimens, were investigated. values differed significantly according to PCP status. Overall, a value of 36 allowed differentiation between PCP and colonization with sensitivity and specificity of 71.3% and 77.1%, respectively. A value of less than 31 confirmed PCP, whereas no value permitted exclusion. A considerable diversity was uncovered; solid organ transplant (SOT) recipients had significantly higher fungal loads than patients with hematological malignancies. In SOT recipients, a cutoff value of 36 resulted in sensitivity and specificity of 95.0% and 83.3%, respectively. In patients with hematological malignancies, a higher cutoff value of 37 improved sensitivity to 88.5% but reduced specificity to 66.7%. For other conditions, assay validity appeared inferior. Corticosteroid usage was an independent predictor of PCP in a multivariable analysis and was associated with higher fungal loads at PCP expression. Semiquantitative real-time PCR improves differentiation between PCP and colonization in immunocompromised HIV-negative individuals with acute respiratory syndromes. However, heterogeneity in disease evolution requires separate cutoff values across intrinsic and iatrogenic predisposition for predicting non-HIV PCP. Pneumocystis jirovecii is potentially life threatening to an increasing number of individuals with compromised immune systems. This microorganism can cause severe pneumonia in susceptible hosts, including patients with cancer and autoimmune diseases and people undergoing solid organ transplantation. Together, these patients constitute an ever-diverse population. In this paper, we demonstrate that the heterogeneity herein has important implications for how we diagnose and assess the risk of Pneumocystis pneumonia (PCP). Specifically, low loads of microorganisms are sufficient to cause infection in patients with blood cancer compared to those in solid organ recipients. With this new insight into host versus biology, clinicians can manage patients at risk of PCP more accurately. As a result, we take a significant step toward offering precision medicine to a vulnerable patient population. One the one hand, these patients have propensity for adverse effects from antimicrobial treatment. On the other hand, this population is susceptible to life-threatening infections, including PCP.
Topics: Aged; Female; Humans; Immunocompromised Host; Male; Middle Aged; Molecular Diagnostic Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity
PubMed: 34346746
DOI: 10.1128/Spectrum.00026-21 -
BMC Pulmonary Medicine Apr 2016Pulmonary infections caused by Pneumocystis jirovecii in immunocompromised host can be associated with cysts, pneumatoceles and air leaks that can progress to... (Review)
Review
Extra corporeal membrane oxygenation to facilitate lung protective ventilation and prevent ventilator-induced lung injury in severe Pneumocystis pneumonia with pneumomediastinum: a case report and short literature review.
BACKGROUND
Pulmonary infections caused by Pneumocystis jirovecii in immunocompromised host can be associated with cysts, pneumatoceles and air leaks that can progress to pneumomediastinum and pneumothoraxes. In such cases, it can be challenging to maintain adequate gas exchange by conventional mechanical ventilation and at the same time prevent further ventilator-induced lung injury. We report a young HIV positive male with poorly compliant lungs and pneumomediastinum secondary to severe Pneumocystis infection, rescued with veno-venous extra corporeal membrane oxygenation (V-V ECMO).
CASE PRESENTATION
A 26 year old male with no significant past medical history was admitted with fever, cough and shortness of breath. He initially required non-invasive ventilation for respiratory failure. However, his respiratory function progressively deteriorated due to increasing pulmonary infiltrates and development of pneumomediastinum, eventually requiring endotracheal intubation and invasive ventilation. Despite attempts at optimizing gas exchange by ventilatory maneuvers, patients' pulmonary parameters worsened necessitating rescue ECMO therapy. The introduction of V-V ECMO facilitated the use of ultra-protective lung ventilation and prevented progression of pneumomediastinum, maintaining optimal gas exchange. It allowed time for the antibiotics to show effect and pulmonary parenchyma to heal. Further diagnostic workup revealed Pneumocystis jirovecii as the causative organism for pneumonia and serology confirmed Human Immunodeficiency Virus infection. Patient was successfully treated with appropriate antimicrobials and de-cannulated after six days of ECMO support.
CONCLUSION
ECMO was an effective salvage therapy in HIV positive patient with an otherwise fatal respiratory failure due to Pneumocystis pneumonia and air leak syndrome.
Topics: Adult; Extracorporeal Membrane Oxygenation; Humans; Lung; Lung Compliance; Male; Mediastinal Emphysema; Pneumonia, Pneumocystis; Respiration, Artificial; Severity of Illness Index; Tomography, X-Ray Computed; Ventilator-Induced Lung Injury
PubMed: 27080997
DOI: 10.1186/s12890-016-0214-4 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... May 2017pneumonia is an opportunistic infection among immunocompromised people. Studies have found that the increased resistance to sulfa drugs of may be associated with the... (Review)
Review
pneumonia is an opportunistic infection among immunocompromised people. Studies have found that the increased resistance to sulfa drugs of may be associated with the mutation of dihydropteroate synthase () gene and dihydrofolate reductase () genes, but the mechanism is still unclear. The mutation of and genes may be the result of sulfa drugs selection or spontaneous genetic polymorphism, and it can be acquired from person-to-person transmission. This article reviews the cause, molecular epidemiology of and gene mutation, and the relationship between and gene mutation and clinical outcomes.
Topics: Dihydropteroate Synthase; Drug Resistance; Humans; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Research; Tetrahydrofolate Dehydrogenase
PubMed: 29488726
DOI: 10.3785/j.issn.1008-9292.2017.10.18 -
BMJ Open Jul 2022pneumonia (PJP) is an opportunistic infection of immunocompromised hosts with significant morbidity and mortality. The current standard of care,...
INTRODUCTION
pneumonia (PJP) is an opportunistic infection of immunocompromised hosts with significant morbidity and mortality. The current standard of care, trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15-20 mg/kg/day, is associated with serious adverse drug events (ADE) in 20%-60% of patients. ADEs include hypersensitivity reactions, drug-induced liver injury, cytopenias and renal failure, all of which can be treatment limiting. In a recent meta-analysis of observational studies, reduced dose TMP-SMX for the treatment of PJP was associated with fewer ADEs, without increased mortality.
METHODS AND ANALYSIS
A phase III randomised, placebo-controlled, trial to directly compare the efficacy and safety of low-dose TMP-SMX (10 mg/kg/day of TMP) with the standard of care (15 mg/kg/day of TMP) among patients with PJP, for a composite primary outcome of change of treatment, new mechanical ventilation, or death. The trial will be undertaken at 16 Canadian hospitals. Data will be analysed as intention to treat. Primary and secondary outcomes will be compared using logistic regression adjusting for stratification and presented with 95% CI.
ETHICS AND DISSEMINATION
This study has been conditionally approved by the McGill University Health Centre; Ethics approval will be obtained from all participating centres. Results will be submitted for publication in a peer-reviewed journal.
TRIAL REGISTRATION NUMBER
NCT04851015.
Topics: Canada; Clinical Trials, Phase III as Topic; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 35863836
DOI: 10.1136/bmjopen-2021-053039 -
Antimicrobial Agents and Chemotherapy Oct 2019
Topics: Caspofungin; Catalytic Domain; Glucosyltransferases; Humans; Mutagenesis, Site-Directed; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 31548211
DOI: 10.1128/AAC.01320-19