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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 -
The Annals of Pharmacotherapy Aug 2016Summarize data on the pathophysiology, treatment, and prevention options for non-AIDS immunocompromised patients who have Pneumocystis jirovecii pneumonia (PJP); review... (Review)
Review
OBJECTIVE
Summarize data on the pathophysiology, treatment, and prevention options for non-AIDS immunocompromised patients who have Pneumocystis jirovecii pneumonia (PJP); review the epidemiology of patients presenting with PJP; and discuss the first and second-line pharmacological options for treatment and prophylaxis of PJP in this population.
DATA SOURCES
MEDLINE (1989-February 2016) searched. Terms searched included combinations of Pneumocystis jirovecii, Pneumocystis carinii, non-HIV, infected, patients, prevention, prophylaxis, Bactrim, treatment, AIDS, opportunistic, immunocompromised, cancer, and pathophysiology
STUDY SELECTION AND DATA EXTRACTION
Articles included had the most relevant information on PJP pathophysiology, and first-/second-line treatment and prophylactic options. Inclusion criteria were met and evaluated with 43 sources.
DATA SYNTHESIS
P jirovecii has a complicated life-cycle; it seeks to find compromised immune systems in order to replicate, causing life-threatening complications. With immunosuppressive medications coming to market for immunomodulating diseases, PJP has become a prevalent opportunistic infection in the non-HIV population. CD4+ lymphocyte count <200 cells/µL is the primary risk factor for PJP presentation in these patients. With data from clinical trials, trimethoprim/sulfamethoxazole (TMP/SMX) has become the primary treatment and prophylaxis of PJP in the non-HIV population, although second-line options are available.
CONCLUSION
PJP is a health problem that may result in an increased concern as more immunomodulating medications to treat various disease states are developed. Patients on these drugs or those with immunosuppressive diseases should have their CD4+ count monitored. Health care providers should continue to use TMP/SMX as the primary option in non-HIV, immunocompromised patients for treatment and prophylaxis of PJP.
Topics: CD4 Lymphocyte Count; Humans; Immunocompromised Host; Immunosuppressive Agents; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 27242349
DOI: 10.1177/1060028016650107 -
Expert Review of Anti-infective Therapy May 2017Pneumocystis jirovecii is a ubiquitous fungus, which causes pneumonia in humans. Diagnosis was hampered by the inability to culture the organism, and based on... (Review)
Review
Pneumocystis jirovecii is a ubiquitous fungus, which causes pneumonia in humans. Diagnosis was hampered by the inability to culture the organism, and based on microscopic examination of respiratory samples or clinical presentation. New assays can assist in the diagnosis and even aid with the emergence of resistant infections. Areas covered: This manuscript will provide background information on Pneumocystis pneumonia (PcP). Diagnosis, from radiological to non-microbiological (e.g. Lactate dehydrogenase) and microbiological investigations (Microscopy, PCR, β-D-Glucan) will be discussed. Recommendations on prophylactic and therapeutic management will be covered. Expert commentary: PcP diagnosis using microscopy is far from optimal and false negatives will occur. With an incidence of 1% or less, the pre-test probability of not having PcP is 99% and testing is suited to excluding disease. Microscopy provides a high degree of diagnostic confidence but it is not infallible, and its lower sensitivity limits its application. Newer diagnostics (PCR, β-D-Glucan) can aid management and improve performance when testing less invasive specimens, such as upper respiratory samples or blood, alleviating clinical pressure. Combination testing may allow PcP to be both diagnosed and excluded, and molecular testing can assist in the detection of emerging resistant PcP.
Topics: Antifungal Agents; Biomarkers; Dapsone; Disease Management; Humans; Incidence; L-Lactate Dehydrogenase; Microscopy; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Proteoglycans; Radiography, Thoracic; Trimethoprim, Sulfamethoxazole Drug Combination; beta-Glucans
PubMed: 28287010
DOI: 10.1080/14787210.2017.1305887 -
Chest Dec 2020Patients with autoimmune and/or inflammatory diseases (AIIDs) are prone to serious infectious complications such as Pneumocystis jirovecii pneumonia (PJP). In non-HIV... (Review)
Review
Patients with autoimmune and/or inflammatory diseases (AIIDs) are prone to serious infectious complications such as Pneumocystis jirovecii pneumonia (PJP). In non-HIV patients, the prognosis is poorer, and diagnostic tests are of lower sensitivity. Given the low incidence of PJP in AIIDs, with the exception of granulomatosis with polyangiitis, and the non-negligible side effects of chemoprophylaxis, routine prescription of primary prophylaxis is still debated. Absolute peripheral lymphopenia, high doses of corticosteroids, combination with other immunosuppressive agents, and concomitant lung disease are strong predictors for the development of PJP and thus should warrant primary prophylaxis. Trimethoprim-sulfamethoxazole is considered first-line therapy and is the most extensively used drug for PJP prophylaxis. Nevertheless, it may expose patients to side effects. Effective alternative drugs such as atovaquone or aerosolized pentamidine could be used when trimethoprim-sulfamethoxazole is not tolerated or contraindicated. No standard guidelines are available to guide PJP prophylaxis in patients with AIIDs. This review covers the epidemiology, risk factors, and prevention of pneumocystis in the context of AIIDs.
Topics: Antifungal Agents; Autoimmune Diseases; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors
PubMed: 32502592
DOI: 10.1016/j.chest.2020.05.558 -
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 -
Internal Medicine Journal Dec 2014Pneumocystis jirovecii infection (PJP) is a common cause of pneumonia in patients with cancer-related immunosuppression. There are well-defined patients who are at risk... (Review)
Review
Pneumocystis jirovecii infection (PJP) is a common cause of pneumonia in patients with cancer-related immunosuppression. There are well-defined patients who are at risk of PJP due to the status of their underlying malignancy, treatment-related immunosuppression and/or concomitant use of corticosteroids. Prophylaxis is highly effective and should be given to all patients at moderate to high risk of PJP. Trimethoprim-sulfamethoxazole is the drug of choice for prophylaxis and treatment, although several alternative agents are available.
Topics: Adrenal Cortex Hormones; Antibiotic Prophylaxis; Consensus; Drug Administration Schedule; Humans; Immunocompromised Host; Neoplasms; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 25482745
DOI: 10.1111/imj.12599 -
Clinical Transplantation Sep 2019These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management...
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Pneumocystis jiroveci fungal infection transplant recipients. Pneumonia (PJP) may develop via airborne transmission or reactivation of prior infection. Nosocomial clusters of infection have been described among transplant recipients. PJP should not occur during prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX). Without prophylaxis, PJP risk is greatest in the first 6 months after organ transplantation but may develop later. Risk factors include low lymphocyte counts, cytomegalovirus infection (CMV), hypogammaglobulinemia, treated graft rejection or corticosteroids, and advancing patient age (>65). Presentation typically includes fever, dyspnea with hypoxemia, and cough. Chest radiographic patterns generally reveal diffuse interstitial processes best seen by CT scans. Patients generally have PO < 60 mm Hg, elevated serum lactic dehydrogenase (LDH), and elevated serum (1 → 3) β-d-glucan assay. Specific diagnosis uses respiratory specimens with direct immunofluorescent staining; invasive procedures may be required. Quantitative PCR is a useful adjunct to diagnosis. TMP-SMX is the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early. Routine PJP prophylaxis is recommended for at least 6-12 months post-transplant, preferably with TMP-SMX.
Topics: Anti-Bacterial Agents; Humans; Organ Transplantation; Pneumocystis Infections; Pneumocystis carinii; Practice Guidelines as Topic; Societies, Medical; Transplant Recipients
PubMed: 31077616
DOI: 10.1111/ctr.13587 -
The Journal of Antimicrobial... Sep 2016The initiation of systemic antimicrobial treatment of Pneumocystis jirovecii pneumonia (PCP) is triggered by clinical signs and symptoms, typical radiological and...
The initiation of systemic antimicrobial treatment of Pneumocystis jirovecii pneumonia (PCP) is triggered by clinical signs and symptoms, typical radiological and occasionally laboratory findings in patients at risk of this infection. Diagnostic proof by bronchoalveolar lavage should not delay the start of treatment. Most patients with haematological malignancies present with a severe PCP; therefore, antimicrobial therapy should be started intravenously. High-dose trimethoprim/sulfamethoxazole is the treatment of choice. In patients with documented intolerance to this regimen, the preferred alternative is the combination of primaquine plus clindamycin. Treatment success should be first evaluated after 1 week, and in case of clinical non-response, pulmonary CT scan and bronchoalveolar lavage should be repeated to look for secondary or co-infections. Treatment duration typically is 3 weeks and secondary anti-PCP prophylaxis is indicated in all patients thereafter. In patients with critical respiratory failure, non-invasive ventilation is not significantly superior to intubation and mechanical ventilation. The administration of glucocorticoids must be decided on a case-by-case basis.
Topics: Administration, Intravenous; Antifungal Agents; Clindamycin; Hematologic Neoplasms; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 27550993
DOI: 10.1093/jac/dkw158 -
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 -
Trends in Microbiology Dec 2020
Topics: Genome, Fungal; Humans; Lung; Pneumocystis Infections; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 33171104
DOI: 10.1016/j.tim.2020.03.006