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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 -
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 and Infection :... Aug 2023Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in patients without HIV infection. In contrast to PCP in patients infected with HIV, diagnosis is often... (Review)
Review
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in patients without HIV infection. In contrast to PCP in patients infected with HIV, diagnosis is often delayed and illness is associated with increased mortality.
OBJECTIVES
To provide a comprehensive review of clinical presentation, risk factors, diagnostic strategies, and treatment options for PCP in patients without HIV infection.
SOURCES
Web-based literature review on PCP for trials, meta-analyses, and systematic reviews using PubMed. The restriction to the English language was applied.
CONTENT
Common underlying conditions in patients without HIV infection having PCP are haematological malignancies, autoimmune and inflammatory diseases, solid organ or haematopoietic stem cell transplant, and previous corticosteroid exposure. New risk groups include patients receiving monoclonal antibodies and immunomodulating therapies. Patients without HIV infection who have PCP present with rapid onset and progression of pneumonia, increased duration of hospitalization and a significantly higher mortality rate than patients infected with HIV. PCP is diagnosed by a combination of clinical symptoms and radiological as well as mycological features. Results of immunofluorescence microscopy from bronchoalveolar lavage, PCR testing, and computed tomography imaging as well as the evaluation of clinical presentation are required. The established treatment regime consists of trimethoprim and sulfamethoxazole.
IMPLICATIONS
Although the number of patients with immunosuppression due to causes different from HIV is increasing, a simultaneous rise in PCP incidence is observed. In the group of patients without HIV infection, rapid onset of symptoms, a more complex course, and a high mortality rate are recorded. Therefore, the time to diagnosis must be as short as possible to initiate effective therapy promptly. This review aims to raise awareness of PCP in an increasingly affected at-risk group and provides clinicians with a practical guide for efficient diagnosis and targeted therapy. Furthermore, it intends to display current inadequacies in research on the topic of PCP.
Topics: Humans; HIV Infections; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Bronchoalveolar Lavage; Pneumocystis carinii
PubMed: 37086781
DOI: 10.1016/j.cmi.2023.04.015 -
Rheumatology (Oxford, England) Oct 2023To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5...
OBJECTIVES
To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5 antibody-positive DM (anti-MDA5+ DM) patients, and to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS).
METHODS
Anti-MDA5+ DM patients who underwent mNGS or real-time PCR for PJP detection were recruited. The potential risk factors for PJP occurrence and death were analysed via Logistic regression and Cox proportional hazards regression, respectively. The diagnostic efficacy of mNGS was compared with the conventional methods.
RESULTS
91 patients were enrolled and 44 were assigned to PJP+ group. The PJP detection rate was 48.4%. PJP often occurred in the first 3 months (68.2%) of the disease; this period also showed the highest mortality rate (20.5%). Fever and increased lactate dehydrogenase (LDH) were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all P < 0.05). Older age and increased LDH were predictors for mortality in patients with anti-MDA5+ DM and PJP (all P < 0.05). In addition, we found that mNGS had a sensitivity of 100.0% and specificity of 90.0% in diagnosing PJP, with the highest area under the curve of 0.95 (P < 0.001).
CONCLUSION
PJP has high prevalence and mortality in anti-MDA5+ DM. It is crucial for clinicians to identify high-risk patients and promptly institute TMP/SMZ to prevent PJP. mNGS is the preferred approach for pathogen detection in anti-MDA5+ DM when PJP is suspected.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Prevalence; Dermatomyositis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 36734589
DOI: 10.1093/rheumatology/kead063 -
Infectious Disease Clinics of North... Sep 2023Pneumocystis infection manifests predominantly as an interstitial pneumonia in immunocompromised patients. Diagnostic testing in the appropriate clinical context can be... (Review)
Review
Pneumocystis infection manifests predominantly as an interstitial pneumonia in immunocompromised patients. Diagnostic testing in the appropriate clinical context can be highly sensitive and specific and involves radiographic imaging, fungal biomarkers, nucleic acid amplification, histopathology, and lung fluid or tissue sampling. Trimethoprim-sulfamethoxazole remains the first-choice agent for treatment and prophylaxis. Investigation continues to promote a deeper understanding of the pathogen's ecology, epidemiology, host susceptibility, and optimal treatment and prevention strategies in solid organ transplant recipients.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Organ Transplantation; Trimethoprim, Sulfamethoxazole Drug Combination; Immunocompromised Host
PubMed: 37142510
DOI: 10.1016/j.idc.2023.03.005 -
Journal of Molecular Medicine (Berlin,... Oct 2023The transcription factor GATA2 is involved in human diseases ranging from hematopoietic disorders, to cancer, to infectious diseases. GATA2 is one of six GATA-family... (Review)
Review
The transcription factor GATA2 is involved in human diseases ranging from hematopoietic disorders, to cancer, to infectious diseases. GATA2 is one of six GATA-family transcription factors that act as pioneering transcription factors which facilitate the opening of heterochromatin and the subsequent binding of other transcription factors to induce gene expression from previously inaccessible regions of the genome. Although GATA2 is essential for hematopoiesis and lymphangiogenesis, it is also expressed in other tissues such as the lung, prostate gland, gastrointestinal tract, central nervous system, placenta, fetal liver, and fetal heart. Gene or transcriptional abnormalities of GATA2 causes or predisposes patients to several diseases including the hematological cancers acute myeloid leukemia and acute lymphoblastic leukemia, the primary immunodeficiency MonoMAC syndrome, and to cancers of the lung, prostate, uterus, kidney, breast, gastric tract, and ovaries. Recent data has also linked GATA2 expression and mutations to responses to infectious diseases including SARS-CoV-2 and Pneumocystis carinii pneumonia, and to inflammatory disorders such as atherosclerosis. In this article we review the role of GATA2 in the etiology and progression of these various diseases.
PubMed: 37624387
DOI: 10.1007/s00109-023-02359-8 -
Pharmaceutical Patent Analyst Jul 2023Repurposing of approved drugs in a new strategy to combat cancer that leads to savings in time and investment. Atovaquone is a US FDA-approved drug for treatment of...
Repurposing of approved drugs in a new strategy to combat cancer that leads to savings in time and investment. Atovaquone is a US FDA-approved drug for treatment of pneumonia and malaria. Patent US2023017373 describe the use of mito-atovaquone for the treatment of several types of cancer. Mito-atovaquone demonstrated antiproliferative activity in cell lines of pancreatic cancer, lung cancer and brain cancer and inhibited tumor growth in syngeneic mouse models and in animals genetically prone to breast cancer. Mito-atovaquone has the potential to be used successfully in the treatment of various types of tumors.
Topics: Mice; Animals; Atovaquone; Drug Repositioning; Antifungal Agents; Naphthoquinones; Pneumonia, Pneumocystis; Neoplasms; Mitomycin
PubMed: 37801038
DOI: 10.4155/ppa-2023-0015