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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 -
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 -
Clinical Microbiology Reviews Mar 2024is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest... (Review)
Review
is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.
Topics: Female; Humans; Male; Pneumonia, Pneumocystis; Pneumocystis carinii; HIV Infections; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 38235979
DOI: 10.1128/cmr.00101-22 -
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 -
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 -
Expert Review of Anti-infective Therapy Oct 2019: pneumonia (PcP) has classically been described as a serious complication in patients infected with the human immunodeficiency virus (HIV). However, the emerging... (Review)
Review
: pneumonia (PcP) has classically been described as a serious complication in patients infected with the human immunodeficiency virus (HIV). However, the emerging number of conditions associated with immunosuppression has led to its appearance in other patient populations. : This article reviews the most recent publications on PcP in the HIV-infected and HIV-uninfected population, focusing on epidemiology, diagnostic, therapy and prevention. The data discussed here were mainly obtained from a non-systematic review using Medline and references from relevant articles including randomized clinical trials, meta-analyses, observational studies and clinical reviews. : The growing incidence of infection in the HIV-uninfected population suggests the need for new global epidemiological studies in order to identify the true scale of the disease in this population. These data would allow us to improve diagnosis, therapeutic strategies, and clinical management. It is very important that both patients and physicians realize that HIV-uninfected patients are at risk of PcP and that rapid diagnosis and early initiation of treatment are associated with better prognosis. Currently, in-hospital mortality rates are very high: 15% for HIV-infected patients and 50% in some HIV-uninfected patients. Therefore, adequate preventive measures should be implemented to avoid the high mortality rates seen in recent decades.
Topics: AIDS-Related Opportunistic Infections; Animals; HIV Infections; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic
PubMed: 31550942
DOI: 10.1080/14787210.2019.1671823 -
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