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Pharmacoepidemiology and Drug Safety Nov 2023To detect the possible safety signal of purine antimetabolites associated with Pneumocystis jirovecii pneumonia through disproportionality analysis in the FDA Adverse...
PURPOSE
To detect the possible safety signal of purine antimetabolites associated with Pneumocystis jirovecii pneumonia through disproportionality analysis in the FDA Adverse Event Reporting System (FAERS) Database.
METHODS
A case/non-case retrospective disproportionality analysis was performed in the publicly available FAERS database using AERSmine (2004Q1-2021Q3). Four models were developed to explore the signal strength of PAs among different populations with possible confounding factors. Reporting odds ratio (ROR) and Proportional reporting ratio (PRR) was used as the data mining algorithm for the analysis. A value of ROR-1.96SE > 1 and PRR ≥ 2 with an associated X value of 4 or more was considered the threshold for a signal.
RESULTS
A total of 7073 reports associated with Pneumocystis jirovecii pneumonia were present in the database, of which 899 reports were associated with purine antimetabolites. A crude signal strength of ROR 15.76(14.70-16.91) was obtained for purine antimetabolites associated PJP, with the highest signal strength reported with fludarabine and thioguanine [ROR 19.63(17.42-22.13); 19.45(13.21-28.63)]. Stratifying the cases based on autoimmune disorders and the cancer population revealed an ROR of 3.33(2.46-4.50) and 2.93(2.26-3.79) respectively. The highest risk of PJP with use of PAs was observed amongst children with a higher risk of nearly 2 times than the adult population [ROR 11.57(9.16-14.62)].
CONCLUSIONS
Our study provided evidence on the occurrence of PJP with the use of purine antimetabolites among the autoimmune and cancer population. We identified signals for PJP with azathioprine, mercaptopurine, thioguanine, cladribine, fludarabine, and clofarabine. More research with a superior epidemiological study design of a defined population is required to validate these findings.
Topics: Adult; Child; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Thioguanine; Neoplasms; Antimetabolites
PubMed: 37265365
DOI: 10.1002/pds.5647 -
Transplant Infectious Disease : An... Nov 2023CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as an effective treatment in those with refractory or relapsed lymphoma. CD19 CAR-T cell therapy can...
BACKGROUND
CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as an effective treatment in those with refractory or relapsed lymphoma. CD19 CAR-T cell therapy can cause direct and indirect toxic adverse effects and increased risk for infection. Infectious complications and optimal antimicrobial prophylaxis strategies are an ongoing area of investigation.
METHODS
A single-center retrospective cohort study was conducted to review recipients of CD19 CAR-T cell therapy between April 2018 and December 2020. Patient characteristics and clinical outcomes were extracted from the electronic health records.
RESULTS
Infectious complications were identified in 18/50 (36%) recipients with 31 episodes of infection. The median time to infection was 225 days (range 0-614). Bacterial infections were most common with bloodstream infection followed by sinusitis and skin and soft tissue infection. Eight viral infections were identified, most being respiratory viral illnesses. Two fungal infections were identified: Pneumocystis jirovecii pneumonia (PJP) and disseminated fusariosis. Seventeen infections (54.8%) were classified as severe: leading to death, requiring hospitalization, need for empiric intravenous antibiotics, or significant alteration in hospital course. No characteristics were found to be statistically significant risks for infection, although a trend toward significance was seen in prior autologous stem cell transplant recipients (p = .12) and those with recurrent neutropenia (p = .14). Three patients (6%) died from infection.
CONCLUSION
Infections were common after CD19 CAR-T cell therapy and occurred beyond the first year. Further multicenter studies are needed to define infectious risks and optimize antimicrobial prophylaxis recommendations in recipients of CD19 CAR-T cell therapy.
Topics: Humans; Anti-Infective Agents; Antigens, CD19; Cell- and Tissue-Based Therapy; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Retrospective Studies
PubMed: 37987114
DOI: 10.1111/tid.14191 -
Nature Reviews. Rheumatology Jul 2023
Topics: Humans; Rituximab; Pneumonia, Pneumocystis
PubMed: 37217611
DOI: 10.1038/s41584-023-00982-w -
JAMA Nov 2023
Topics: Humans; Pneumonia, Pneumocystis; Chemoprevention
PubMed: 37988090
DOI: 10.1001/jama.2023.18865 -
Clinical Microbiology and Infection :... May 2024Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death. (Review)
Review
BACKGROUND
Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death.
OBJECTIVE
To determine the frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa.
METHODS
We conducted a scoping review of autopsy studies conducted in Africa.
DATA SOURCES
PubMed, Scopus, Web of Science, Embase, Google Scholar, and African Journal Online.
STUDY ELIGIBILITY CRITERIA
The review encompasses studies published from inception to September 2023, and no language restrictions were imposed during the search process. We included studies that reported histopathological or microbiological evidence for the diagnosis of fungal infections and other pathogens.
DATA SYNTHESIS
Data were summarized using descriptive statistics and no meta-analysis was performed.
RESULTS
We examined 30 articles reporting studies conducted between 1991 and 2019, encompassing a total of 13 066 HIV-infected decedents across ten African countries. In five studies, the autopsy type was not specified. Among those studies with specified autopsy types, 20 involved complete diagnostic autopsies, whereas 5 were categorized as partial or minimally invasive autopsies. There were 2333 pathogens identified, with 946 (40.5%) being mycobacteria, 856 (36.7%) fungal, 231 (3.8%) viral, 208 (8.9%) parasitic, and 92 (3.9%) bacterial. Of the 856 fungal pathogens identified, 654 (28.0%) were Cryptococcus species, 167 (7.2%) Pneumocystis jirovecii, 16 (0.69%) Histoplasma species, 15 (0.64%) Aspergillus species, and 4 (0.17%) Candida species. Other major non-fungal pathogens identified were cytomegalovirus 172 (7.37%) and Toxoplasma gondii 173 (7.42%).
CONCLUSIONS
Invasive fungal infections occur in over one-third of people who succumb to HIV in Africa. In addition to cryptococcosis and Pneumocystis jirovecii pneumonia, integrating other priority fungal pathogen detection and management strategies into the broader framework of HIV care in Africa is recommended. This involves increasing awareness regarding the impact of fungal infections in advanced HIV disease and strengthening diagnostic and treatment capacity.
Topics: Humans; Autopsy; Africa; HIV Infections; Mycoses; Fungi; AIDS-Related Opportunistic Infections
PubMed: 38145865
DOI: 10.1016/j.cmi.2023.12.016 -
BioRxiv : the Preprint Server For... Feb 2024pneumonia (PjP) poses a serious risk to individuals with compromised immune systems, such as individuals with HIV/AIDS or undergoing immunosuppressive therapies for...
pneumonia (PjP) poses a serious risk to individuals with compromised immune systems, such as individuals with HIV/AIDS or undergoing immunosuppressive therapies for cancer or solid organ transplants. Severe PjP triggers excessive lung inflammation, resulting in lung function decline and consequential alveolar damage, potentially culminating in acute respiratory distress syndrome. Non-HIV patients face a 30-60%mortality rate, emphasizing the need for a deeper understanding of inflammatory responses in PjP. Prior research emphasized macrophages in infections, neglecting neutrophils' role in tissue damage. Consequently, the overemphasis on macrophages led to an incomplete understanding of the role of neutrophils and inflammatory responses. In the current investigation, our RNAseq studies on a murine surrogate model of PjP revealed heightened activation of the NLRP3 inflammasome and NETosis cell death pathways in their lungs. Immunofluorescence staining confirmed Neutrophil Extracellular Trap (NET) presence in the lungs of the -infected mice, validating our findings. Moreover, isolated neutrophils exhibited NETosis when directly stimulated with . While isolated NETs did not compromise viability, our data highlight the potential role of neutrophils in promoting inflammation during pneumonia through NLRP3 inflammasome assembly and NETosis. These pathways, essential for inflammation and pathogen elimination, bear the risk of uncontrolled activation leading to excessive tissue damage and persistent inflammation. This pioneering study is the first to identify the formation of NETs and inflammasomes during infection, paving the way for comprehensive investigations into treatments aimed at mitigating lung damage and augmenting survival rates for individuals with PjP.
PubMed: 38405901
DOI: 10.1101/2024.02.16.580773 -
BMC Infectious Diseases Jul 2023Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation... (Review)
Review
OBJECTIVE
Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for PJP.
METHODS
A comprehensive electronic literature search of Web of Knowledge, PubMed, Cochrane Library, CNKI and Wanfang data was performed. Bivariate analysis was conducted to calculate the pooled sensitivity, specificity, diagnostic odds ratio (DOR), the area under the summary receiver operator characteristic (SROC) curve and the Q-point value (Q*).
RESULTS
The literature search resulted in 9 studies with a total of 1343 patients, including 418 cases diagnosed with PJP and 925 controls. The pooled sensitivity of mNGS for diagnosis of PJP was 0.974 [95% confidence interval (CI), 0.953-0.987]. The pooled specificity was 0.943 (95% CI, 0.926-0.957), the DOR was 431.58 (95% CI, 186.77-997.27), the area under the SROC curve was 0.987, and the Q* was 0.951. The I test indicated no heterogeneity between studies. The Deek funnel test suggested no potential publication bias. Subgroup analyses showed that the area under the SROC curve of mNGS for diagnosis of PJP in immunocompromised and non-HIV patients was 0.9852 and 0.979, respectively.
CONCLUSIONS
Current evidence indicates that mNGS exhibits excellent accuracy for the diagnosis of PJP. The mNGS is a promising tool for assessment of PJP in both immunocompromised and non-HIV patients.
Topics: Humans; Correlation of Data; High-Throughput Nucleotide Sequencing; Immunocompromised Host; Knowledge; Pneumonia, Pneumocystis
PubMed: 37430211
DOI: 10.1186/s12879-023-08440-4 -
Annals of the Rheumatic Diseases Jan 2024Life-threatening antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with rapidly progressive glomerulonephritis (RPGN) and/or alveolar haemorrhage...
Short-term effectiveness and safety of rituximab versus cyclophosphamide for life-threatening ANCA-associated vasculitis: a propensity score analysis of the real-world nationwide database.
OBJECTIVES
Life-threatening antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with rapidly progressive glomerulonephritis (RPGN) and/or alveolar haemorrhage (AH) has a poor prognosis. Rituximab (RTX) is as effective as cyclophosphamide (CY) in remission induction therapy; however, the effectiveness and safety of RTX have not been established in life-threatening AAV. This study aimed to investigate the short-term effectiveness and safety of RTX in life-threatening AAV with RPGN and/or AH.
METHODS
Between April 2018 and March 2020, cases treated with systemic glucocorticoids and RTX or intravenous CY (IVCY) was extracted from a Japanese nationwide inpatient database. Effectiveness was evaluated by in-hospital mortality and severe renal dysfunction requiring haemodialysis (HD) at discharge. Safety was evaluated by the in-hospital incidence of infections. The propensity score (PS) for RTX was estimated. Multivariable Cox and logistic regression with adjustment for PS were conducted to estimate the association of RTX with outcomes.
RESULTS
From 16 001 612 hospitalised records, 687 life-threatening AAV cases were extracted. No significant difference in in-hospital mortality (adjusted HR 1.06; 95% CI 0.62 to 1.80) was found between the groups. Although the RTX group had a lower risk of fungal infections (adjusted OR (aOR) 0.45; 95% CI 0.23 to 0.84) and pneumocystis pneumonia (aOR 0.58; 95% CI 0.32 to 1.00), they might have an increased risk of severe renal dysfunction requiring HD at discharge (aOR 2.58; 95% CI 1.02 to 6.91).
CONCLUSIONS
In life-threatening AAV, RTX has similar short-term effectiveness on mortality to IVCY. Although RTX might have a lower risk of fungal infections and pneumocystis pneumonia, the short-term renal prognosis might be inferior to IVCY.
Topics: Humans; Rituximab; Pneumonia, Pneumocystis; Propensity Score; Treatment Outcome; Cyclophosphamide; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Kidney Diseases; Remission Induction
PubMed: 37726117
DOI: 10.1136/ard-2023-224472 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Oct 2023, an important opportunistic fungal pathogen that parasitizes in multiple mammalian lungs, may cause life-threatening pneumonia (PCP) and even death among... (Review)
Review
, an important opportunistic fungal pathogen that parasitizes in multiple mammalian lungs, may cause life-threatening pneumonia (PCP) and even death among immunocompromised individuals. With the rapid development of high-throughput sequencing and multi-omics technologies, systematic comparative analyses of genome, transcriptome, and whole-genome sequencing results demonstrate that is a type of obligate biotrophic fungi, and requires obtaining nutrition from hosts. In addition, sexual reproduction is an essential process for survival, production and transmission, and asexual reproduction facilitates survival, which provides new insights into understanding of the whole developmental process of in the host lung and inter-host transmission of . This review summarizes the advances in the reproduction mode of and underlying mechanisms, which provides insights into prevention and treatment of PCP, notably for the prophylaxis against nosocomial transmission of PCP.
Topics: Humans; Lung; Pneumocystis; Pneumonia, Pneumocystis
PubMed: 38148544
DOI: 10.16250/j.32.1374.2022289 -
JAMA Jun 2024Severe pulmonary infections, including COVID-19, community-acquired pneumonia, influenza, and Pneumocystis pneumonia, are a leading cause of death among adults...
IMPORTANCE
Severe pulmonary infections, including COVID-19, community-acquired pneumonia, influenza, and Pneumocystis pneumonia, are a leading cause of death among adults worldwide. Pulmonary infections in critically ill patients may cause septic shock, acute respiratory distress syndrome, or both, which are associated with mortality rates ranging between 30% and 50%.
OBSERVATIONS
Corticosteroids mitigate the immune response to infection and improve outcomes for patients with several types of severe pulmonary infections. Low-dose corticosteroids, defined as less than or equal to 400 mg hydrocortisone equivalent daily, can reduce mortality of patients with severe COVID-19, community-acquired pneumonia, and Pneumocystis pneumonia. A randomized clinical trial of 6425 patients hospitalized with COVID-19 who required supplemental oxygen or noninvasive or invasive mechanical ventilation reported that dexamethasone 6 mg daily for 10 days decreased 28-day mortality (23% vs 26%). A meta-analysis that included 7 randomized clinical trials of 1689 patients treated in the intensive care unit for severe bacterial community-acquired pneumonia reported that hydrocortisone equivalent less than or equal to 400 mg daily for 8 days or fewer was associated with lower 30-day mortality compared with placebo (10% vs 16%). In a meta-analysis of 6 randomized clinical trials, low-dose corticosteroids were associated with lower mortality rates compared with placebo for patients with HIV and moderate to severe Pneumocystis pneumonia (13% vs 25%). In a predefined subgroup analysis of a trial of low-dose steroid treatment for septic shock, patients with community-acquired pneumonia randomized to 7 days of intravenous hydrocortisone 50 mg every 6 hours and fludrocortisone 50 μg daily had decreased mortality compared with the placebo group (39% vs 51%). For patients with acute respiratory distress syndrome caused by various conditions, low-dose corticosteroids were associated with decreased in-hospital mortality (34% vs 45%) according to a meta-analysis of 8 studies that included 1091 patients. Adverse effects of low-dose corticosteroids may include hyperglycemia, gastrointestinal bleeding, neuropsychiatric disorders, muscle weakness, hypernatremia, and secondary infections.
CONCLUSIONS AND RELEVANCE
Treatment with low-dose corticosteroids is associated with decreased mortality for patients with severe COVID-19 infection, severe community-acquired bacterial pneumonia, and moderate to severe Pneumocystis pneumonia (for patients with HIV). Low-dose corticosteroids may also benefit critically ill patients with respiratory infections who have septic shock, acute respiratory distress syndrome, or both.
PubMed: 38865154
DOI: 10.1001/jama.2024.6096