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Pharmacotherapy Nov 2022Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications... (Review)
Review
Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications utilized for the treatment of IBD affect the immune system, potentially further increasing the risk of PJP. Recommendations for prophylaxis against PJP in this patient population are based upon limited evidence, and risk factors for PJP development are not well-agreed upon. The purpose of this systematic review was to consolidate and evaluate the evidence for PJP prophylaxis in patients with IBD. An electronic literature search was performed, and 29 studies were included in the review, of which 24 were case reports or case series. Combined data from five cohort studies showed an absolute risk of developing PJP to be 0.07%. The majority of patients who developed PJP were receiving corticosteroids at the time of diagnosis (76%). The number of concomitant immunosuppressants received at time of PJP diagnosis varied from one to four. All studies reporting treatment of PJP utilized sulfamethoxazole-trimethoprim. Of the 27 studies reporting mortality data, 19% of patients died. Given the lack of conclusive data regarding risk factors for PJP development and the overall low incidence of PJP in patients with IBD, it is recommended to assess the patient's risk on a case-by-case basis to determine whether PJP prophylaxis is warranted.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; Inflammatory Bowel Diseases; Immunosuppressive Agents
PubMed: 36222368
DOI: 10.1002/phar.2733 -
Journal of Fungi (Basel, Switzerland) Dec 2021While has been recognized as both a ubiquitous commensal fungus in immunocompetent mammalian hosts and a major opportunistic pathogen in humans responsible for severe...
While has been recognized as both a ubiquitous commensal fungus in immunocompetent mammalian hosts and a major opportunistic pathogen in humans responsible for severe pneumonias in immunocompromised patients, in pigs its epidemiology and association with pulmonary diseases have been rarely reported. Nevertheless, the fungus can be quite abundant in porcine populations with up to 51% of prevalence reported so far. The current study was undertaken to longitudinally quantify f. sp. and other pulmonary pathogens in a cohort of 50 pigs from five Austrian farms (i.e., 10 pigs per farm) with a history of respiratory disease at five time points between the first week and the fourth month of life. The fungus was present as early as the suckling period (16% and 26% of the animals in the first and the third week, respectively), yet not in a high amount. Over time, both the organism load (highest 4.4 × 10 copies/mL) and prevalence (up to 88% of positive animals in the third month) increased in each farm. The relative prevalence of various coinfection patterns was significantly different over time. The current study unravelled a complex co-infection history involving and other pulmonary pathogens in pigs, suggesting a relevant role of the fungus in the respiratory disease scenario of this host.
PubMed: 35049984
DOI: 10.3390/jof8010043 -
Journal of Infection and Chemotherapy :... Dec 2020The objective of this study was to describe the recent epidemiology of Pneumocystis pneumonia (PCP) in Japan using a nationwide database.
OBJECTIVES
The objective of this study was to describe the recent epidemiology of Pneumocystis pneumonia (PCP) in Japan using a nationwide database.
METHODS
We extracted data of inpatients with PCP from the Diagnostic Procedure Combination database, a national inpatient database in Japan, from January 2010 to December 2016.
RESULTS
During the study period, 4293 PCP patients were identified, including 4073 adults and 220 children. In adults, the most common comorbidity was hematologic malignancy (31%), followed by diabetes mellitus (30%), rheumatic/collagen diseases (26%), and solid organ tumors (18%). In children, there were few patients with rheumatic diseases (5%) or diabetes mellitus (2%), but immunodeficiency (without human immunodeficiency virus) was more common (28%). Few biological products were used for adult and pediatric patients; CD20 inhibitors, TNF-α inhibitors, interleukin receptor inhibitors, and CTLA-4 inhibitor were used for 8.6% and 2.4%, 1.3% and 0%, 1.2% and 4.7%, and 0.2% and 0% of adult and pediatric patients, respectively. Based on data stratified by bed count, the annual numbers of PCP patients in Japan were estimated as 2221 adults and 123 pediatric patients. The mortality was higher in adults (27%) than in pediatric patients (21%) (P = 0.041).
CONCLUSIONS
The underlying disease and mortality were apparently different between adult and pediatric PCP patients.
Topics: Adult; Child; Comorbidity; HIV Infections; Humans; Japan; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies
PubMed: 32753118
DOI: 10.1016/j.jiac.2020.07.006 -
Biomedicines Feb 2024This study aimed to develop a simple predictive model for early identification of the risk of adverse outcomes in kidney transplant-associated pneumonia (PCP) patients.
BACKGROUND
This study aimed to develop a simple predictive model for early identification of the risk of adverse outcomes in kidney transplant-associated pneumonia (PCP) patients.
METHODS
This study encompassed 103 patients diagnosed with PCP, who received treatment at our hospital between 2018 and 2023. Among these participants, 20 were categorized as suffering from severe PCP, and, regrettably, 13 among them succumbed. Through the application of machine learning techniques and multivariate logistic regression analysis, two pivotal variables were discerned and subsequently integrated into a nomogram. The efficacy of the model was assessed via receiver operating characteristic (ROC) curves and calibration curves. Additionally, decision curve analysis (DCA) and a clinical impact curve (CIC) were employed to evaluate the clinical utility of the model. The Kaplan-Meier (KM) survival curves were utilized to ascertain the model's aptitude for risk stratification.
RESULTS
Hematological markers, namely Procalcitonin (PCT) and C-reactive protein (CRP)-to-albumin ratio (CAR), were identified through machine learning and multivariate logistic regression. These variables were subsequently utilized to formulate a predictive model, presented in the form of a nomogram. The ROC curve exhibited commendable predictive accuracy in both internal validation (AUC = 0.861) and external validation (AUC = 0.896). Within a specific threshold probability range, both DCA and CIC demonstrated notable performance. Moreover, the KM survival curve further substantiated the nomogram's efficacy in risk stratification.
CONCLUSIONS
Based on hematological parameters, especially CAR and PCT, a simple nomogram was established to stratify prognostic risk in patients with renal transplant-related PCP.
PubMed: 38397968
DOI: 10.3390/biomedicines12020366 -
Medical Science Monitor : International... Aug 2022BACKGROUND Sepsis is a serious threat to human life, particularly in immunocompromised patients; hence, early diagnosis and targeted treatment are important. Metagenomic...
BACKGROUND Sepsis is a serious threat to human life, particularly in immunocompromised patients; hence, early diagnosis and targeted treatment are important. Metagenomic next-generation sequencing (NGS) has significant advantages over traditional diagnostic methods. This study investigated the clinical value of NGS for pathogen identification in immunocompromised patients with sepsis. MATERIAL AND METHODS From July 2020 to September 2021, 90 consecutive patients with sepsis were enrolled in this prospective study. The patients were divided into 2 groups: an immunocompromised group (n=30) and an immunocompetent group (n=60). The pathogens causing sepsis were concurrently identified using NGS and traditional diagnostic methods. The pathogen detection rates and the spectrum of pathogens identified were compared according to the method of detection and between the immunocompromised and immunocompetent groups. RESULTS Of the 90 patients, 77 (86%) were positive for 1 or more pathogens using NGS, and 50 (56%) were positive using traditional detection methods. The positivity rate of sputum and bronchoalveolar lavage fluid was higher than that of blood samples. Pneumocystis jirovecii and cytomegalovirus infections were more common in the immunocompromised group than in the immunocompetent group. CONCLUSIONS The performance of NGS in identifying pathogens for patients with sepsis is better than that of traditional detection methods, especially in immunocompromised patients. Pneumocystis jirovecii and cytomegalovirus infections are more common in immunocompromised patients.
Topics: Bronchoalveolar Lavage Fluid; Cytomegalovirus Infections; High-Throughput Nucleotide Sequencing; Humans; Immunocompromised Host; Pneumocystis carinii; Prospective Studies; Sepsis
PubMed: 35957507
DOI: 10.12659/MSM.937041 -
Journal of Medical Microbiology Dec 2021Pathogen-associated molecular patterns' (PAMPs) are microbial signatures that are recognized by host myeloid C-type lectin receptors (CLRs). These CLRs interact with...
Pathogen-associated molecular patterns' (PAMPs) are microbial signatures that are recognized by host myeloid C-type lectin receptors (CLRs). These CLRs interact with micro-organisms via their carbohydrate recognition domains (CRDs) and engage signalling pathways within the cell resulting in pro-inflammatory and microbicidal responses. In this article, we extend our laboratory study of additional CLRs that recognize fungal ligands against and and their purified major surface glycoproteins (Msgs). To study the potential of newly synthesized hFc-CLR fusions on binding to and its Msg. A library of new synthesized hFc-CLR fusions was screened against and organisms and their purified major surface glycoproteins (Msgs) found on the respective fungi via modified ELISA. Immunofluorescence assay (IFA) was implemented and quantified to verify results. mRNA expression analysis by quantitative PCR (q-PCR) was employed to detect respective CLRs found to bind fungal organisms in the ELISA and determine their expression levels in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model. We detected a number of the CLR hFc-fusions displayed significant binding with and organisms, and similarly to their respective Msgs. Significant organism and Msg binding was observed for CLR members C-type lectin domain family 12 member A (CLEC12A), Langerin, macrophage galactose-type lectin-1 (MGL-1), and specific intracellular adhesion molecule-3 grabbing non-integrin homologue-related 3 (SIGNR3). Immunofluorescence assay (IFA) with the respective CLR hFc-fusions against whole life forms corroborated these findings. Lastly, we surveyed the mRNA expression profiles of the respective CLRs tested above in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model and determined that macrophage galactose type C-type lectin (), implicated in recognizing terminal N-acetylgalactosamine (GalNAc) found in the glycoproteins of microbial pathogens was significantly up-regulated during infection. The data herein add to the growing list of CLRs recognizing and provide insights for further study of organism/host immune cell interactions.
Topics: Animals; Mice; Fungal Proteins; Galactose; Host-Pathogen Interactions; Lectins, C-Type; Membrane Glycoproteins; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; RNA, Messenger
PubMed: 34889727
DOI: 10.1099/jmm.0.001470 -
Medical Mycology Dec 2021Pneumocystis jirovecii is associated with non-noxious colonization or severe pneumonia in immunocompromised hosts. Epidemiological investigations have been hampered by...
UNLABELLED
Pneumocystis jirovecii is associated with non-noxious colonization or severe pneumonia in immunocompromised hosts. Epidemiological investigations have been hampered by the lack of a standardized typing scheme. Thus, only partial molecular data on Spanish P. jirovecii cases are available. Recently, a new ISHAM consensus multilocus sequence typing scheme (MLST) targeting β-TUB, mt26S, CYB, and SOD with a publicly accessible database has been launched to overcome this problem. The molecular epidemiology of P. jirovecii from immunocompromised patients either colonized (n = 50) or having pneumonia (n = 36) seen between 2014 and 2018 at a single center in Barcelona, Spain, was studied. The new ISHAM consensus MSLT scheme was used to investigate the local epidemiology and identify possible unnoticed outbreaks. Mutations in the DHPS gene, not included in the scheme but giving information about potential sulfa treatment failure, were also studied. The study assigned 32 sequence types (ST) to 72.2% pneumonia and 56% colonization cases. The most frequent STs were ST21 (18.5%), ST22 (14.8%), and ST37(14.8%). For non-unique STs, ST3, ST30 and ST31 were found only in pneumonia cases, whereas ST27 was associated exclusively to colonizations. Despite 38 patients sharing similar STs, only two were involved in a potential cross transmission event. No DHPS mutations were identified. The new consensus typing scheme was useful to ascertain the molecular epidemiology of P. jirovecii in our center revealing a high genetic diversity and the potential association of specific STs to colonization and pneumonia cases.
LAY SUMMARY
A newly described MLST scheme aims at providing a standardized tool to study and compare Pneumocystis jirovecii epidemiology. A high diversity among P. jirovecii isolates from patients in Barcelona, Spain, and a potential association between specific STs and infection/colonization were identified.
Topics: Animals; Multilocus Sequence Typing; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Tertiary Care Centers
PubMed: 34698858
DOI: 10.1093/mmy/myab065 -
Antimicrobial Agents and Chemotherapy Oct 2020, the opportunistic fungus that causes pneumonia (PCP) in humans, is a significant contributor to morbidity and mortality in immunocompromised patients. Given the...
, the opportunistic fungus that causes pneumonia (PCP) in humans, is a significant contributor to morbidity and mortality in immunocompromised patients. Given the profound deleterious inflammatory effects of the major β-glucan cell wall carbohydrate constituents of through Dectin-1 engagement and downstream caspase recruitment domain-containing protein 9 (CARD9) immune activation, we sought to determine whether the pharmacodynamic activity of the known CARD9 inhibitor BRD5529 might have a therapeutic effect on macrophage innate immune signaling and subsequent downstream anti-inflammatory activity. The small-molecule inhibitor BRD5529 was able to significantly reduce both phospho-p38 and phospho-pERK1 signaling and tumor necrosis factor alpha (TNF-α) release during stimulation of macrophages with cell wall β-glucans.
Topics: CARD Signaling Adaptor Proteins; Humans; Immunity, Innate; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; beta-Glucans
PubMed: 32839216
DOI: 10.1128/AAC.01210-20 -
Clinical Infectious Diseases : An... Mar 2021Pneumocystis jirovecii pneumonia (PCP) causes substantive morbidity in immunocompromised patients. The EORTC/MSGERC convened an expert group to elaborate consensus...
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) causes substantive morbidity in immunocompromised patients. The EORTC/MSGERC convened an expert group to elaborate consensus definitions for Pneumocystis disease for the purpose of interventional clinical trials and epidemiological studies and evaluation of diagnostic tests.
METHODS
Definitions were based on the triad of host factors, clinical-radiologic features, and mycologic tests with categorization into probable and proven Pneumocystis disease, and to be applicable to immunocompromised adults and children without human immunodeficiency virus (HIV). Definitions were formulated and their criteria debated and adjusted after public consultation. The definitions were published within the 2019 update of the EORTC/MSGERC Consensus Definitions of Invasive Fungal Disease. Here we detail the scientific rationale behind the disease definitions.
RESULTS
The diagnosis of proven PCP is based on clinical and radiologic criteria plus demonstration of P. jirovecii by microscopy using conventional or immunofluorescence staining in tissue or respiratory tract specimens. Probable PCP is defined by the presence of appropriate host factors and clinical-radiologic criteria, plus amplification of P. jirovecii DNA by quantitative real-time polymerase chain reaction (PCR) in respiratory specimens and/or detection of β-d-glucan in serum provided that another invasive fungal disease and a false-positive result can be ruled out. Extrapulmonary Pneumocystis disease requires demonstration of the organism in affected tissue by microscopy and, preferably, PCR.
CONCLUSIONS
These updated definitions of Pneumocystis diseases should prove applicable in clinical, diagnostic, and epidemiologic research in a broad range of immunocompromised patients without HIV.
Topics: Adult; Child; Diagnostic Tests, Routine; HIV; HIV Infections; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Sensitivity and Specificity
PubMed: 33709126
DOI: 10.1093/cid/ciaa1805 -
RoFo : Fortschritte Auf Dem Gebiete Der... Nov 2021Clinical signs and symptoms related to invasive fungal disease are nonspecific and need to be followed up by appropriate diagnostic procedures. The goal of this study...
Radiological CT Patterns and Distribution of Invasive Pulmonary Aspergillus, Non-Aspergillus, Cryptococcus and Pneumocystis Jirovecii Mold Infections - A Multicenter Study.
PURPOSE
Clinical signs and symptoms related to invasive fungal disease are nonspecific and need to be followed up by appropriate diagnostic procedures. The goal of this study was to analyze CT imaging patterns in invasive fungal infections and their correlation with the immune status and clinical outcome.
MATERIALS AND METHODS
We performed a retrospective multicenter study including 85 consecutive patients with invasive pulmonary fungal infection (2011-2014). Lung patterns on computed tomography (CT) scans were classified according to the Fleischner Society glossary. The patients were grouped according to immune status (neutropenia, steroid therapy, organ transplant recipient, and other cause) and outcome (positive outcome, progressive disease, and death). The Chi square test or Fisher exact test was used. Bonferroni correction was applied.
RESULTS
The total number of patients with invasive Aspergillus and non-Aspergillus infection (IANA), Pneumocystis jirovecii pneumonia (PCP), and Cryptococcus (CRY) was 60, 22, and 3, respectively. Patients with IANA demonstrated significantly more nodules (93 % vs. 59 %, p = 0.001), significantly fewer ground glass opacities (58 % vs. 96 %, p = 0.005), and significantly fewer positive lymph nodes (5 % vs. 41 %, p < 0.001) than patients with PCP. All patients with PCP and CRY had a favorable outcome. Patients with IANA and an adverse outcome demonstrated significantly more nodules with halo sign than patients with IANA and a favorable outcome (42.5 % vs. 15.9 %, p < 0.0001). Interestingly, patients with IANA and a favorable outcome had a higher prevalence of pulmonary infarction than patients with an adverse outcome (8 % vs. 1 %, p = 0.047). Patients with neutropenia showed significantly more consolidations (66 %) than organ transplant recipients (27 %, p = 0.045).
CONCLUSION
Patients with IANA showed a higher prevalence of nodules and a lower prevalence of ground glass opacities than patients with PCP. In patients with IANA, nodules with halo sign were associated with an adverse outcome. Patients with neutropenia showed generally more consolidations, but the consolidations were not associated with an adverse outcome.
KEY POINTS
· Nodules, ground glass opacities, and consolidations are common CT findings in all invasive pulmonary fungal infections.. · There is no pattern that is unique for one specific pathogen, although nodules are more predominant in IANA and Cryptococcus, and ground glass opacities are more predominant in PCP patients.. · Immune status had an impact on CT findings in fungal pneumonia with less consolidation in patients after organ transplantation compared to patients with neutropenia.. · Nodules with a halo sign are associated with a worse outcome..
CITATION FORMAT
· Obmann VC, Bickel F, Hosek N et al. Radiological CT Patterns and Distribution of Invasive Pulmonary Aspergillus, Non-Aspergillus, Cryptococcus and Pneumocystis Jirovecii Mold Infections - A Multicenter Study. Fortschr Röntgenstr 2021; 193: 1304 - 1314.
Topics: Aspergillus; Cryptococcus; Humans; Lung; Pneumocystis carinii; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 34034346
DOI: 10.1055/a-1482-8336