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International Journal of Molecular... Nov 2023pneumonia (PCP) is a significant cause of morbidity and mortality in immunocompromised people. The widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for the...
pneumonia (PCP) is a significant cause of morbidity and mortality in immunocompromised people. The widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment and prophylaxis of opportunistic infections (including PCP) has led to an increased selection of TMP-SMZ-resistant microorganisms. Sulfa/sulfone resistance has been demonstrated to result from specific point mutations in the gene. This study aims to investigate the presence of gene mutations among isolates from Bulgarian patients with PCP. A total of 326 patients were examined via real-time PCR targeting the mitochondrial large subunit gene and further at the locus. DNA was detected in 50 (15.34%) specimens. A 370 bp locus fragment was successfully amplified in 21 samples from 19 PCP-positive patients, which was then purified, sequenced, and used for phylogenetic analysis. Based on the sequencing analysis, all ( = 21) isolates showed genotype 1 (the wild type, with the nucleotide sequence ACA CGG CCT at codons 55, 56, and 57, respectively). In conclusion, infections caused by mutants potentially resistant to sulfonamides are still rare events in Bulgaria. genotype 1 at codons 55 and 57 is the predominant strain in the country.
Topics: Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Dihydropteroate Synthase; Bulgaria; Phylogeny; Mutation; Trimethoprim, Sulfamethoxazole Drug Combination; Codon
PubMed: 38069248
DOI: 10.3390/ijms242316927 -
Zhonghua Jie He He Hu Xi Za Zhi =... Dec 2023Pneumocystis pneumonia (PCP) is an opportunistic infection caused by and is the most common fungal infection in HIV/AIDS patients. With the routine use of...
Pneumocystis pneumonia (PCP) is an opportunistic infection caused by and is the most common fungal infection in HIV/AIDS patients. With the routine use of antiretroviral therapy (ART), the incidence of PCP infection in HIV/AIDS patients has decreased and the prognosis has improved significantly. On the other hand, the use of chemoradiotherapy and immunotherapy in patients with cancer, post-transplantation and autoimmune diseases are increasing dramatically, which has led to a similar increase in the incidence of PCP in these non-HIV/AIDS patients. There is a global shift in research on PCP from HIV-infected co-infected PCP (HIV-PCP) to non-HIV-infected co-infected PCP. The clinical course of non-HIV-PCP is rapid and severe, and the morbidity and mortality rates are higher than those of HIV-PCP. Studies have shown that 90% of non-HIV-PCP patients have a history of glucocorticoid use prior to infection, such as in patients with hematologic malignancies, solid organ transplants, and rheumatic diseases, and that long-term high-dose glucocorticoid use is an important risk for PCP susceptibility. Clinical practice has shown that PCP often occurs during the tapering of glucocorticoids, and a higher proportion of patients develop diffuse pulmonary lesions and, in more severe cases suffer from life-threatening acute respiratory failure. The pathogenesis of non-HIV infections associated with PCP is not yet clarified, and there is a lack of effective therapeutic practices that require further investigation.
Topics: Humans; Acquired Immunodeficiency Syndrome; Pneumonia, Pneumocystis; Glucocorticoids; AIDS-Related Opportunistic Infections; HIV Infections
PubMed: 38044054
DOI: 10.3760/cma.j.cn112147-20230826-00108 -
Methods in Molecular Biology (Clifton,... 2024Atovaquone is an FDA-approved antiparasitic and antifungal therapeutic that is currently used as a prophylactic agent to prevent Pneumocystis carinii pneumonia (PCP)...
Atovaquone is an FDA-approved antiparasitic and antifungal therapeutic that is currently used as a prophylactic agent to prevent Pneumocystis carinii pneumonia (PCP) infections in acute myeloid leukemia (AML) patients after receiving hematopoietic stem cell transplantation (HSCT). Recent studies have shown that atovaquone has shown potential as an anticancer agent. The high variability in atovaquone bioavailability prompts the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients. Briefly, an organic-based solvent system is used to precipitate protein and extract the atovaquone content from each patient-derived plasma sample. After completing a second stage of sample dilution (5000-fold overall), a 2 μL volume of the plasma extract is analyzed using the liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based bioanalytical method described.
Topics: Humans; Child; Atovaquone; Pneumonia, Pneumocystis; Tandem Mass Spectrometry; Chromatography, Liquid; Antifungal Agents; Leukemia, Myeloid, Acute; Plant Extracts
PubMed: 38036811
DOI: 10.1007/978-1-0716-3541-4_7 -
Journal of Pediatric Health Care :... 2024This case describes a four-month-old male who was admitted to the pediatric intensive care unit for acute respiratory failure in the setting of a co-infection requiring...
Use of Metagenomic Next-Generation Sequencing in the Identification of Pneumocystis Jiroveci Pneumonia in a Previously Healthy Infant Diagnosed With X-Linked Hyper-IgM Syndrome.
This case describes a four-month-old male who was admitted to the pediatric intensive care unit for acute respiratory failure in the setting of a co-infection requiring increased ventilatory support. Immunodeficiency workup demonstrated poor vaccination response and low immunoglobulin titers. mNGS via Karius® test was positive for Pneumocystis jiroveci (PJP), Parvovirus, and Bocavirus. The patient was successfully treated with trimethoprim-sulfamethoxazole and prednisone. Genetic workup via Invitae panel confirmed that the patient had X-linked Hyper-IgM Syndrome. Use of mNGS can help with early identification of pathogens that conventional testing does not detect, even in patients not already identified as immunocompromised.
Topics: Humans; Male; Pneumonia, Pneumocystis; Pneumocystis carinii; Infant; Hyper-IgM Immunodeficiency Syndrome, Type 1; High-Throughput Nucleotide Sequencing; Metagenomics; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 38032574
DOI: 10.1016/j.pedhc.2023.09.009 -
BMC Infectious Diseases Nov 2023Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to...
OBJECTIVE
Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj.
METHODS
A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed.
RESULTS
Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support.
CONCLUSION
The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent.
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; DNA Copy Number Variations; Bronchoalveolar Lavage Fluid; Polymerase Chain Reaction; Pneumocystis; Respiratory Distress Syndrome; Pneumocystis carinii
PubMed: 38012564
DOI: 10.1186/s12879-023-08580-7 -
Medical Mycology Dec 2023Bronchoalveolar lavage fluid (BALF) is a standard respiratory sample for diagnosing invasive fungal diseases like Pneumocystis pneumonia (PCP) and invasive pulmonary... (Observational Study)
Observational Study
Bronchial aspirate obtained during bronchoscopy yields increased fungal load compared to bronchoalveolar lavage fluid in patients at risk of invasive aspergillosis and Pneumocystis pneumonia.
Bronchoalveolar lavage fluid (BALF) is a standard respiratory sample for diagnosing invasive fungal diseases like Pneumocystis pneumonia (PCP) and invasive pulmonary aspergillosis (IPA). However, procedural variations exist across medical centers and wards. This study aimed to compare the diagnostic potential of BALF and bronchial aspirate (BA) obtained during bronchoscopy in 173 patients suspected of fungal infections. A prospective observational study was conducted from April 2020 to November 2021. BALF and BA were collected during bronchoscopy and subjected to direct examination, fungal culture, Aspergillus fumigatus qPCR (AfqPCR), and Pneumocystis jirovecii qPCR (PjqPCR). Galactomannan detection was performed on BALF. Patients were classified based on established European Organization for Research and Treatment of Cancer (EORTC) criteria. Out of 173 patients, 75 tested positive for at least one test in BA or BALF. For Aspergillus, proportion of positive AfqPCR (14.5% vs. 9.2%; P < 0.0001) and fungal loads (Cq of 31.3 vs. 32.8; P = 0.0018) were significantly higher in BA compared to BALF. For Pneumocystis, fungal loads by PjqPCR was also higher in BA compared to BALF (Cq of 34.2 vs. 35.7; P = 0.003). BA only detected A. fumigatus and P. jirovecii in 12 (42.9%) and 8 (19.5%) patients, respectively. BA obtained during a BAL procedure can be a suitable sample type for increased detection of P. jirovecii and A. fumigatus by qPCR. The use of BA in diagnostic algorithms requires further investigation in prospective studies.
Topics: Humans; Bronchoalveolar Lavage Fluid; Pneumonia, Pneumocystis; Bronchoscopy; Prospective Studies; Sensitivity and Specificity; Aspergillosis; Invasive Pulmonary Aspergillosis; Pneumocystis carinii; Mannans
PubMed: 37996394
DOI: 10.1093/mmy/myad120 -
Diagnostic Microbiology and Infectious... Feb 2024(1-3)-Beta-D Glucan (BDG) detection has shown to be a highly effective tool to diagnose invasive fungal infections. Therefore, this study aimed to compare clinical...
Evaluation of the Performance of the Dynamiker Fungus (1-3)-β-D-Glucan and Fungitell Assay for Diagnosis of Candidemia: Need for New Cut-off Development and Test Validation.
(1-3)-Beta-D Glucan (BDG) detection has shown to be a highly effective tool to diagnose invasive fungal infections. Therefore, this study aimed to compare clinical characteristics of the Fungitell (FA) and Dynamiker Fungus (1-3)-β-D-Glucan assay (DFA) for the diagnosis of candidemia. Using DFA and FA, the BDG levels of 57 serum samples from case and control groups were determined. The kappa coefficient (κ) and Spearman's rank correlation (r) were used to examine the consistency of assays on a quantitative and qualitative level, respectively. The sensitivity, specificity, and accuracy were 94.6 %, 65.0 %, and 87.7% for DFA, and 94.6 %, 75.0 %, and 89.4 % for FA, respectively. The performance of the DFA for the diagnosis of candidemia was highly consistent with that of the FA, both quantitatively (r: 0.9) and qualitatively (kappa = 0.78). Collectively, the DFA assay performed excellently in comparison to the FA for the diagnosis of candidemia.
Topics: Humans; Candidemia; Glucans; Sensitivity and Specificity; Fungi; Pneumocystis carinii; beta-Glucans
PubMed: 37992564
DOI: 10.1016/j.diagmicrobio.2023.116118 -
BMC Pulmonary Medicine Nov 2023Pneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant...
BACKGROUND
Pneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant recipients. Recent years have witnessed a rising incidence of PCP in this vulnerable population, leading to graft loss and increased mortality. Immunosuppression, which is essential in transplant recipients, heightens susceptibility to viral and opportunistic infections, magnifying the clinical challenge. Concurrently, the global impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been profound. Kidney transplant recipients have faced severe outcomes when infected with SARS-CoV-2, often requiring intensive care. Co-infection with COVID-19 and PCP in this context represents a complex clinical scenario that requires precise management strategies, involving a delicate balance between immunosuppression and immune activation. Although there have been case reports on management of COVID-19 and PCP in kidney transplant recipients, guidance on how to tackle these infections when they occur concurrently remains limited.
CASE PRESENTATIONS
We have encountered four kidney transplant recipients with concurrent COVID-19 and PCP infection. These patients received comprehensive treatment that included adjustment of their maintenance immunosuppressive regimen, anti-pneumocystis therapy, treatment for COVID-19 and other infections, and symptomatic and supportive care. After this multifaceted treatment strategy, all of these patients improved significantly and had favorable outcomes.
CONCLUSIONS
We have successfully managed four kidney transplant recipients co-infected with COVID-19 and PCP. While PCP is a known complication of immunosuppressive therapy, its incidence in patients with COVID-19 highlights the complexity of dual infections. Our findings suggest that tailored immunosuppressive regimens, coupled with antiviral and antimicrobial therapies, can lead to clinical improvement in such cases. Further research is needed to refine risk assessment and therapeutic strategies, which will ultimately enhance the care of this vulnerable population.
Topics: Humans; Pneumonia, Pneumocystis; COVID-19; Kidney Transplantation; Retrospective Studies; Transplant Recipients; SARS-CoV-2; Immunosuppressive Agents; Pneumocystis carinii
PubMed: 37990199
DOI: 10.1186/s12890-023-02764-2 -
Annals of Clinical Microbiology and... Nov 2023The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected...
OBJECTIVE
The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results.
METHODS
This was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort.
RESULTS
Two hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4 T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG.
CONCLUSIONS
Serum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Glucans; Retrospective Studies; beta-Glucans; Lung Neoplasms; HIV Infections; Lung Diseases, Interstitial
PubMed: 37986091
DOI: 10.1186/s12941-023-00650-7 -
American Journal of Transplantation :... Apr 2024Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort...
Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.
Topics: Female; Humans; Middle Aged; Europe; Glucocorticoids; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Transplant Recipients; Male; Aged
PubMed: 37977229
DOI: 10.1016/j.ajt.2023.11.003