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International Journal of Molecular... Apr 2023This multicenter retrospective study aimed to clarify the prognostic factors for mortality and changes in treatment modalities and disease activities after the onset of...
This multicenter retrospective study aimed to clarify the prognostic factors for mortality and changes in treatment modalities and disease activities after the onset of pneumonia (PCP) in patients with rheumatoid arthritis (RA). Data regarding the clinical background, treatment modalities, and disease activity indicators of RA at the onset of PCP (baseline), and 6 months and 12 months after treatment were extracted. Of the 37 patients with RA-PCP (median age, 69 years; 73% female), chemical prophylaxis was administered to 8.1%. Six patients died during PCP treatment. The serum C-reactive protein (CRP) levels and the prednisolone (PDN) dose at baseline in the PCP death group were significantly higher than those in the survivor group. Multivariate analysis using a Cox regression model showed that PDN dose at baseline was a predictor of death from PCP in patients with RA. During the 12 months from baseline, the RA disease activity significantly decreased. A high dose of corticosteroids for RA may result in a poor prognosis when PCP is complicated. In the future, preventive administration techniques must be established for patients with RA who need PCP prevention.
Topics: Humans; Female; Aged; Male; Pneumonia, Pneumocystis; Retrospective Studies; Cohort Studies; Pneumocystis carinii; Prognosis; Arthritis, Rheumatoid; Prednisolone
PubMed: 37108561
DOI: 10.3390/ijms24087399 -
The Journal of Infectious Diseases May 2022We describe the prevalence of Pneumocystis jirovecii in mother-infant pairs of very low birth weight newborns <32 weeks gestation. Molecular and microscopic methods were...
We describe the prevalence of Pneumocystis jirovecii in mother-infant pairs of very low birth weight newborns <32 weeks gestation. Molecular and microscopic methods were used for detection of P. jirovecii in patients' specimens. Pneumocystis DNA was detected in 8 nasopharyngeal aspirates (14%) of 56 newborns and in 7 oral washes (21%) of 34 mothers. Pneumocystis detection immediately after birth suggests the possibility of its transplacental transmission. Compared to noncolonized infants, more frequent occurrence of bronchopulmonary dysplasia was seen in colonized infants (P = .02), suggesting a potential clinical importance of this pathogen in abnormal lung development.
Topics: Gestational Age; Humans; Infant; Infant, Newborn; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; Respiratory Distress Syndrome
PubMed: 33857302
DOI: 10.1093/infdis/jiab209 -
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 -
The Cochrane Database of Systematic... Apr 2015Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10% to 20% during the initial infection and this increases substantially with the need for mechanical ventilation. It has been suggested that corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality in these patients.
OBJECTIVES
To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxaemia (arterial oxygen partial pressure < 70 mmHg or alveolar-arterial gradient > 35 mmHg on room air).
SEARCH METHODS
For the original review we searched The Cochrane Library (2004, Issue 4), MEDLINE (January 1980 to December 2004) and EMBASE (January 1985 to December 2004) without language restrictions. We further reviewed the reference lists from previously published overviews, searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts in the field and searched the reference lists of identified publications for citations of additional relevant articles.In this update of our review, we searched the above-mentioned databases in September 2010 and April 2014 for trials published since our original review. We also searched for ongoing trials in ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (ICTRP). We searched for conference abstracts via AEGIS.
SELECTION CRITERIA
Randomised controlled trials that compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, and reported mortality data. We excluded trials in patients with no or mild hypoxaemia (arterial oxygen partial pressure > 70 mmHg or an alveolar-arterial gradient < 35 mmHg on room air) and trials with a follow-up of less than 30 days.
DATA COLLECTION AND ANALYSIS
Two teams of review authors independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups using a random-effects model.In this update of our review, we used the GRADE methodology to assess evidence quality.
MAIN RESULTS
Of 2029 screened records, we included seven studies in the review and six in the meta-analysis. Risk of bias varied: the randomisation and allocation process was often not clearly described, five of seven studies were double-blind and there was almost no missing data. The quality of the evidence for mortality was high. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval (CI) 0.32 to 0.98) at one month and 0.59 (95% CI 0.41 to 0.85) at three to four months of follow-up. In adults, to prevent one death, numbers needed to treat are nine patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. The three largest trials provided moderate quality data on the need for mechanical ventilation, with a risk ratio of 0.38 (95% CI 0.20 to 0.73) in favour of adjunctive corticosteroids. One study was conducted in infants, suggesting a risk ratio for death in hospital of 0.81 (95% CI 0.51 to 1.29; moderate quality evidence).
AUTHORS' CONCLUSIONS
The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but the evidence from this review suggests a beneficial effect for adult patients with substantial hypoxaemia. There is insufficient evidence on the effect of adjunctive corticosteroids on survival in infants.
Topics: AIDS-Related Opportunistic Infections; Adrenal Cortex Hormones; Adult; Chemotherapy, Adjuvant; Humans; Hypoxia; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 25835432
DOI: 10.1002/14651858.CD006150.pub2 -
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 -
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 -
MBio Dec 2016Fungi in the genus Pneumocystis live in the lungs of mammals, where they can cause a fatal pneumonia (PCP [Pneumocystis pneumonia]) in hosts with compromised immune...
UNLABELLED
Fungi in the genus Pneumocystis live in the lungs of mammals, where they can cause a fatal pneumonia (PCP [Pneumocystis pneumonia]) in hosts with compromised immune systems. The absence of a continuous in vitro culture system for any species of Pneumocystis has led to limited understanding of these fungi, especially for the discovery of new therapies. We recently reported that Pneumocystis carinii, Pneumocystis murina, and most significantly, Pneumocystis jirovecii lack both enzymes necessary for myo-inositol biosynthesis but contain genes with homologies to fungal myo-inositol transporters. Since myo-inositol is essential for eukaryotic viability, the primary transporter, ITR1, was functionally and structurally characterized in P. carinii The predicted structure of P. carinii ITR1 (PcITR1) contained 12 transmembrane alpha-helices with intracellular C and N termini, consistent with other inositol transporters. The apparent K was 0.94 ± 0.08 (mean ± standard deviation), suggesting that myo-inositol transport in P. carinii is likely through a low-affinity, highly selective transport system, as no other sugars or inositol stereoisomers were significant competitive inhibitors. Glucose transport was shown to use a different transport system. The myo-inositol transport was distinct from mammalian transporters, as it was not sodium dependent and was cytochalasin B resistant. Inositol transport in these fungi offers an attractive new drug target because of the reliance of the fungi on its transport, clear differences between the mammalian and fungal transporters, and the ability of the host to both synthesize and transport this critical nutrient, predicting low toxicity of potential inhibitors to the fungal transporter.
IMPORTANCE
myo-Inositol is a sugarlike nutrient that is essential for life in most organisms. Humans and microbes alike can obtain it by making it, which involves only 2 enzymes, by taking it from the environment by a transport process, or by recycling it from other cellular constituents. Inspection of the genomes of the pathogenic fungi of the genus Pneumocystis showed that these pneumonia-causing parasites could not make myo-inositol, as they lacked the 2 enzymes. Instead, we found evidence of inositol transporters, which would import the sugar from the lungs where the fungi reside. In the present report, we characterized the transport of myo-inositol in the fungus and found that the transporter was highly selective for myo-inositol and did not transport any other molecules. The transport was distinct from that in mammalian cells, and since mammals can both make and transport myo-inositol, while Pneumocystis fungi must transport it, this process offers a potential new drug target.
Topics: Biological Transport; Carbohydrate Metabolism; Cytochalasin B; Fungal Proteins; Glucose; Inositol; Kinetics; Membrane Transport Proteins; Pneumocystis carinii
PubMed: 27965450
DOI: 10.1128/mBio.01851-16 -
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 -
Current Opinion in Microbiology Dec 2017Pneumocystis jirovecii causes clinical pneumonia in immunocompromised hosts. Despite this, the inability to cultivate this organism in vitro has likely hindered the... (Review)
Review
Pneumocystis jirovecii causes clinical pneumonia in immunocompromised hosts. Despite this, the inability to cultivate this organism in vitro has likely hindered the field in ascertaining the true impact of Pneumocystis in human infection. However the recent release of the genome as well as in advances in understanding host genetics, and other risk factors for infection and robust experimental models of disease have shed new light on the impact of this fungal pathogen as to better define populations at risk. This review will highlight these recent advances as well as highlight future needed areas of research.
Topics: Animals; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 29136537
DOI: 10.1016/j.mib.2017.10.019 -
Trends in Parasitology Oct 2021The clinical picture of the fungal disease, Pneumocystis pneumonia, resembles the course of coronavirus disease 2019 (COVID-19), presenting a diagnostic challenge in the...
The clinical picture of the fungal disease, Pneumocystis pneumonia, resembles the course of coronavirus disease 2019 (COVID-19), presenting a diagnostic challenge in the pandemic era. We discuss the concern of Pneumocystis jirovecii and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coinfection, their similarities, and the impact of immunosuppression, with a suggested diagnostic pathway for their suspected coinfection.
Topics: COVID-19; Coinfection; Humans; Immunosuppression Therapy; Pandemics; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 34364804
DOI: 10.1016/j.pt.2021.07.010