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Expert Opinion on Pharmacotherapy Aug 2021: (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts. Risk factors for pneumonia (PJP) include HIV, organ transplant,... (Review)
Review
: (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts. Risk factors for pneumonia (PJP) include HIV, organ transplant, malignancy, certain inflammatory or rheumatologic conditions, and associated therapies and conditions that result in cell-mediated immune deficiency. Clinical signs of PJP are nonspecific and definitive diagnosis requires direct detection of the organism in lower respiratory secretions or tissue. First-line therapy for prophylaxis and treatment remains trimethoprim-sulfamethoxazole (TMP-SMX), though intolerance or allergy, and rarely treatment failure, may necessitate alternate therapeutics, such as dapsone, pentamidine, atovaquone, clindamycin, primaquine and most recently, echinocandins as adjunctive therapy. In people living with HIV (PLWH), adjunctive corticosteroid use in treatment has shown a mortality benefit.: This review article covers the epidemiology, pathophysiology, diagnosis, microbiology, prophylaxis indications, prophylactic therapies, and treatments.: TMP-SMX has been first-line therapy for treating and preventing pneumocystis for decades. However, its adverse effects are not uncommon, particularly during treatment. Second-line therapies may be better tolerated, but often sacrifice efficacy. Echinocandins show some promise for new combination therapies; however, further studies are needed to define optimal antimicrobial therapy for PJP as well as the role of corticosteroids in those without HIV.
Topics: Humans; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33870843
DOI: 10.1080/14656566.2021.1915989 -
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 -
Seminars in Respiratory and Critical... Feb 2020remains an important fungal pathogen in a broad range of immunocompromised hosts. The natural reservoir of infection remains unknown. Pneumonia (PJP) develops via... (Review)
Review
remains an important fungal pathogen in a broad range of immunocompromised hosts. The natural reservoir of infection remains unknown. Pneumonia (PJP) develops via airborne transmission or reactivation of inadequately treated infection. Nosocomial clusters of infection have been described among immunocompromised hosts. Subclinical infection or colonization may occur. Pneumocystis pneumonia occurs most often within 6 months of organ transplantation and with intensified or prolonged immunosuppression, notably with corticosteroids. Infection is also common during neutropenia and low-lymphocyte counts, with hypogammaglobulinemia, and following cytomegalovirus (CMV) infection. The clinical presentation generally includes fever, dyspnea with hypoxemia, and nonproductive cough. Chest radiographic patterns are best visualized by computed tomography (CT) scan with diffuse interstitial processes. Laboratory examination reveals hypoxemia, elevated serum lactic dehydrogenase levels, and elevated serum (1→3) β-D-glucan assays. Specific diagnosis is achieved using respiratory specimens with direct immunofluorescent staining; invasive procedures may be required and are important to avoid unnecessary therapies. Quantitative nucleic acid amplification is a useful adjunct to diagnosis but may be overly sensitive. Trimethoprim-sulfamethoxazole (TMP-SMX) remains the drug of choice for therapy; drug allergy should be documented before resorting to alternative therapies. Adjunctive corticosteroids may be useful early in the clinical course; aggressive reductions in immunosuppression may provoke immune reconstitution syndromes. Pneumocystis pneumonia (PJP) prophylaxis is recommended and effective for immunocompromised individuals in the most commonly affected risk groups.
Topics: Humans; Immunocompromised Host; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 32000290
DOI: 10.1055/s-0039-3399559 -
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 -
JAMA Jul 2023
Topics: Adult; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumocystis carinii; Chemoprevention
PubMed: 37358837
DOI: 10.1001/jama.2023.9844 -
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 -
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 -
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