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Journal of Fungi (Basel, Switzerland) Nov 2022remains an important fungal pathogen in immunocompromised hosts. The environmental reservoir remains unknown. Pneumonia (PJP) results from airborne transmission,... (Review)
Review
remains an important fungal pathogen in immunocompromised hosts. The environmental reservoir remains unknown. Pneumonia (PJP) results from airborne transmission, including in nosocomial clusters, or with reactivation after an inadequately treated infection. most often occurs within 6 months of organ transplantation, with intensified or prolonged immunosuppression, notably with corticosteroids and following cytomegalovirus (CMV) infections. Infection may be recognized during recovery from neutropenia and lymphopenia. Invasive procedures may be required for early diagnosis and therapy. Despite being a well-established entity, aspects of the pathogenesis of PJP remain poorly understood. The goal of this review is to summarize the data on the pathogenesis of PJP, review the strengths and weaknesses of the pertinent diagnostic modalities, and discuss areas for future research.
PubMed: 36354934
DOI: 10.3390/jof8111167 -
Medical Mycology Nov 2020Pneumocystis jirovecii can cause life-threatening pneumonia in immunocompromised patients. Traditional diagnostic testing has relied on staining and direct visualization... (Review)
Review
Pneumocystis jirovecii can cause life-threatening pneumonia in immunocompromised patients. Traditional diagnostic testing has relied on staining and direct visualization of the life-forms in bronchoalveolar lavage fluid. This method has proven insensitive, and invasive procedures may be needed to obtain adequate samples. Molecular methods of detection such as polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and antibody-antigen assays have been developed in an effort to solve these problems. These techniques are very sensitive and have the potential to detect Pneumocystis life-forms in noninvasive samples such as sputum, oral washes, nasopharyngeal aspirates, and serum. This review evaluates 100 studies that compare use of various diagnostic tests for Pneumocystis jirovecii pneumonia (PCP) in patient samples. Novel diagnostic methods have been widely used in the research setting but have faced barriers to clinical implementation including: interpretation of low fungal burdens, standardization of techniques, integration into resource-poor settings, poor understanding of the impact of host factors, geographic variations in the organism, heterogeneity of studies, and limited clinician recognition of PCP. Addressing these barriers will require identification of phenotypes that progress to PCP and diagnostic cut-offs for colonization, generation of life-form specific markers, comparison of commercial PCR assays, investigation of cost-effective point of care options, evaluation of host factors such as HIV status that may impact diagnosis, and identification of markers of genetic diversity that may be useful in diagnostic panels. Performing high-quality studies and educating physicians will be crucial to improve the rates of diagnosis of PCP and ultimately to improve patient outcomes.
Topics: Humans; Immunoassay; Immunocompromised Host; Microbiological Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sensitivity and Specificity; Specimen Handling; Staining and Labeling
PubMed: 32400869
DOI: 10.1093/mmy/myaa024 -
Respiration; International Review of... 2018The substantial decline in the Pneumocystis jirovecii pneumonia (PCP) incidence in HIV-infected patients after the introduction of antiretroviral therapy (ART) in... (Review)
Review
The substantial decline in the Pneumocystis jirovecii pneumonia (PCP) incidence in HIV-infected patients after the introduction of antiretroviral therapy (ART) in resource-rich settings and the growing number of non-HIV-infected immunocompromised patients at risk leads to considerable epidemiologic changes with clinical, diagnostic, and treatment consequences for physicians. HIV-infected patients usually develop a subacute course of disease, while non-HIV-infected immunocompromised patients are characterized by a rapid disease progression with higher risk of respiratory failure and higher mortality. The main symptoms usually include exertional dyspnea, dry cough, and subfebrile temperature or fever. Lactate dehydrogenase may be elevated. Typical findings on computed tomography scans of the chest are bilateral ground-glass opacities with or without cystic lesions, which are usually associated with the presence of AIDS. Empiric treatment should be initiated as soon as PCP is suspected. Bronchoalveolar lavage has a higher diagnostic yield compared to induced sputum. Immunofluorescence is superior to conventional staining. A combination of different diagnostic tests such as microscopy, polymerase chain reaction, and (1,3)-β-D-glucan is recommended. Trimeth-oprim/sulfamethoxazole for 21 days is the treatment of choice in adults and children. Alternative treatment regimens include dapsone with trimethoprim, clindamycin with primaquine, atovaquone, or pentamidine. Patients with moderate to severe disease should receive adjunctive corticosteroids. In newly diagnosed HIV-infected patients with PCP, ART should be initiated as soon as possible. In non-HIV-infected immunocompromised patients, improvement of the immune status should be discussed (e.g., temporary reduction of immunosuppressive agents). PCP prophylaxis is effective and depends on the immune status of the patient and the underlying immunocompromising disease.
Topics: Adult; Bronchoalveolar Lavage; Child; Drug Therapy, Combination; Fluorescent Antibody Technique; HIV Infections; HIV Seronegativity; Humans; Immunocompromised Host; Lung; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography, Thoracic; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 29635251
DOI: 10.1159/000487713 -
Avicenna Journal of Medicine Jan 2023pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has... (Review)
Review
pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has been a decline in pneumonia incidence in HIV since the introduction of antiretroviral medications. However, its incidence is increasing in non-HIV immunocompromised patients including those with solid organ transplantation, hematopoietic stem cell transplantation, solid organ tumors, autoimmune deficiencies, and primary immunodeficiency disorders. We aim to review and summarize the etiology, epidemiology, clinical presentation, diagnosis, and management of pneumonia in HIV, and non-HIV patients. HIV patients usually have mild-to-severe symptoms, while non-HIV patients present with a rapidly progressing disease. Induced sputum or bronchoalveolar lavage fluid can be used to make a definitive diagnosis of pneumonia. Trimethoprim-sulfamethoxazole is considered to be the first-line drug for treatment and has proven to be highly effective for pneumonia prophylaxis in both HIV and non-HIV patients. Pentamidine, atovaquone, clindamycin, and primaquine are used as second-line agents. While several diagnostic tests, treatments, and prophylactic regimes are available at our disposal, there is need for more research to prevent and manage this disease more effectively.
PubMed: 36969352
DOI: 10.1055/s-0043-1764375 -
Current Opinion in Infectious Diseases Aug 2019Pneumocystis pneumonia (PCP) is a frequent opportunistic infection associated with a high mortality rate. PCP is of increasing importance in non-HIV immunocompromised... (Review)
Review
PURPOSE OF REVIEW
Pneumocystis pneumonia (PCP) is a frequent opportunistic infection associated with a high mortality rate. PCP is of increasing importance in non-HIV immunocompromised patients, who present with severe respiratory distress with low fungal loads. Molecular detection of Pneumocystis in broncho-alveolar lavage (BAL) has become an important diagnostic tool, but quantitative PCR (qPCR) needs standardization.
RECENT FINDINGS
Despite a high negative predictive value, the positive predictive value of qPCR is moderate, as it also detects colonized patients. Attempts are made to set a cut-off value of qPCR to discriminate between PCP and colonization, or to use noninvasive samples or combined strategies to increase specificity.
SUMMARY
It is easy to set a qPCR cut-off for HIV-infected patients. In non-HIV IC patients, a gain in specificity could be obtained by combining strategies, that is, qPCR on BAL and a noninvasive sample, or qPCR and serum beta-1,3-D-glucan dosage.
Topics: Bronchoalveolar Lavage Fluid; Coinfection; Disease Management; HIV Infections; Humans; Immunocompromised Host; Molecular Diagnostic Techniques; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Sensitivity and Specificity
PubMed: 31107250
DOI: 10.1097/QCO.0000000000000559 -
Clinical Microbiology and Infection :... Jan 2022Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection commonly affecting immunocompromised people. Diagnosis usually requires invasive techniques to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection commonly affecting immunocompromised people. Diagnosis usually requires invasive techniques to obtain respiratory specimens. Minimally invasive detection tests have been proposed, but their operating characteristics are poorly described.
OBJECTIVES
To systematically review and meta-analyse the performance of minimally invasive PCP detection tests to inform diagnostic algorithms.
DATA SOURCES
Medline, Embase, Cochrane Library (inception to 15 October 2020).
STUDY ELIGIBILITY CRITERIA
Studies of minimally invasive PCP detection tests were included if they contained a minimum of ten PCP cases.
PARTICIPANTS
Adults at risk of PCP.
TESTS
Non-invasive PCP detection tests.
REFERENCE STANDARD
Diagnosis using the combination of clinical and radiographical features with invasive sampling.
ASSESSMENT OF RISK BIAS
Using the QUADAS-2 tool.
METHODS
We used bivariate and, when necessary, univariate analysis models to estimate diagnostic test sensitivity and specificity.
RESULTS
Fifty-two studies were included; most studies (40) comprised exclusively human immunodeficiency virus (HIV) -infected individuals; nine were mixed (HIV and non-HIV), two were non-HIV and one study did not report HIV status. Sampling sites included induced sputum, nasopharyngeal aspirate, oral wash and blood. The four testing modalities evaluated were cytological staining, fluorescent antibody, PCR and lactate dehydrogenase. Induced sputum had the most data available; this modality was both highly sensitive at 99% (95% CI 51%-100%) and specific at 96% (95% CI 88%-99%). Induced sputum cytological staining had moderate sensitivity at 50% (95% CI 39%-61%) and high specificity at 100% (95% CI 100%-100%), as did fluorescent antibody testing with sensitivity 74% (95% CI 62%-87%) and specificity 100% (95% CI 91%-100%).
CONCLUSION
There are several promising minimally invasive PCP diagnostic tests available, some of which may reduce the need for invasive respiratory sampling. Understanding the operating characteristics of these tests can augment current diagnostic strategies and help establish a more confident clinical diagnosis of PCP. Further studies in non-HIV infected populations are needed.
Topics: Adult; HIV Infections; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Sensitivity and Specificity; Sputum
PubMed: 34464734
DOI: 10.1016/j.cmi.2021.08.017 -
Annals of Hematology Jun 2021Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii...
Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematologic malignancies and solid tumors: 2020 updated guidelines of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO/DGHO).
Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii pneumonia (PcP). As bacterial resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, administration of antibacterial prophylaxis has become a matter of discussion. This guideline constitutes an update of the 2013 published guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). It gives an overview about current strategies for antibacterial prophylaxis in cancer patients while taking into account the impact of antibacterial prophylaxis on the human microbiome and resistance development. Current literature published from January 2012 to August 2020 was searched and evidence-based recommendations were developed by an expert panel. All recommendations were discussed and approved in a consensus conference of the AGIHO prior to publication. As a result, we present a comprehensive update and extension of our guideline for antibacterial and PcP prophylaxis in cancer patients.
Topics: Anti-Bacterial Agents; Antineoplastic Agents; Drug Resistance, Bacterial; Fluoroquinolones; Germany; Hematologic Neoplasms; Hematology; Humans; Medical Oncology; Microbiota; Pneumocystis carinii; Pneumonia, Pneumocystis; Societies, Medical
PubMed: 33846857
DOI: 10.1007/s00277-021-04452-9 -
Annals of Hematology Feb 2021To ensure the safety of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT), evidence-based recommendations on infectious complications after... (Review)
Review
Prophylaxis, diagnosis and therapy of infections in patients undergoing high-dose chemotherapy and autologous haematopoietic stem cell transplantation. 2020 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).
To ensure the safety of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT), evidence-based recommendations on infectious complications after HDC/ASCT are given. This guideline not only focuses on patients with haematological malignancies but also addresses the specifics of HDC/ASCT patients with solid tumours or autoimmune disorders. In addition to HBV and HCV, HEV screening is nowadays mandatory prior to ASCT. For patients with HBs antigen and/or anti-HBc antibody positivity, HBV nucleic acid testing is strongly recommended for 6 months after HDC/ASCT or for the duration of a respective maintenance therapy. Prevention of VZV reactivation by vaccination is strongly recommended. Cotrimoxazole for the prevention of Pneumocystis jirovecii is supported. Invasive fungal diseases are less frequent after HDC/ASCT, therefore, primary systemic antifungal prophylaxis is not recommended. Data do not support a benefit of protective room ventilation e.g. HEPA filtration. Thus, AGIHO only supports this technique with marginal strength. Fluoroquinolone prophylaxis is recommended to prevent bacterial infections, although a survival advantage has not been demonstrated.
Topics: Germany; Hematologic Neoplasms; Hematology; Hematopoietic Stem Cell Transplantation; Hepacivirus; Hepatitis B; Hepatitis B Antibodies; Hepatitis B virus; Hepatitis C; Humans; Medical Oncology; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; RNA, Viral; Societies, Medical; Transplantation, Autologous; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33079221
DOI: 10.1007/s00277-020-04297-8 -
Clinical Microbiology and Infection :... Sep 2020Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring semi-invasive respiratory sampling. The serum 1,3-β-D-glucan (BDG) assay has been proposed as a minimally invasive test for the presumptive diagnosis of PJP.
METHOD
We carried out a systematic review and meta-analysis using articles in the English language published between January 1960 and September 2019. We estimated the pooled sensitivity and specificity of BDG testing using a bivariate random effects approach and compared test performance in human immunodeficiency virus (HIV) and non-HIV subgroups with meta-regression. Data from the pooled sensitivity and specificity were transformed to generate pre- and post-test probability curves.
RESULTS
Twenty-three studies were included. The pooled sensitivity and specificity of serum BDG testing for PJP were 91% (95%CI 87-94%) and 79% (95%CI 72-84%) respectively. The sensitivity in patients with HIV was better than in patients without (94%, 95%CI 91-96%) versus 86% (95%CI 78-91%) (p 0.02), with comparable specificity (83%, 95%CI 69-92% versus 83%, 95%CI 72-90%) (p 0.10). A negative BDG was only associated with a low post-test probability of PJP (≤5%) when the pre-test probability was low to intermediate (≤20% in non-HIV and ≤50% in HIV).
CONCLUSIONS
Among patients with a higher likelihood of PJP, the pooled sensitivity of BDG is insufficient to exclude infection. Similarly, for most cases, the pooled specificity is inadequate to diagnose PJP. Understanding the performance of BDG in the population being investigated is therefore essential to optimal clinical decision-making.
Topics: Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Sensitivity and Specificity; Serologic Tests; beta-Glucans
PubMed: 32479781
DOI: 10.1016/j.cmi.2020.05.024