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Open Forum Infectious Diseases Jun 2024Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitor (BTKi) for...
Risk of Invasive Fungal Infections in Patients With Chronic Lymphocytic Leukemia Treated With Bruton Tyrosine Kinase Inhibitors: A Case-Control Propensity Score-Matched Analysis.
BACKGROUND
Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitor (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom a BTKi is now the first-line recommended therapy.
METHODS
We queried TriNetX, a global research network database, to identify adult patients with CLL using the code (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs.
RESULTS
Among 5358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi versus 3.5% among patients not on a BTKi at 5 years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of pneumonia (PJP) (0.5% vs 0.3%, = .02) and invasive candidiasis (3.5% vs 2.7%, = .012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively.
CONCLUSIONS
We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are, however, low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKis are required to identify at-risk patients and preventive, cost-effective interventions.
PubMed: 38887474
DOI: 10.1093/ofid/ofae115 -
Current HIV Research Jun 2024Vitamin D deficiency and/or insufficiency (hypovitaminosis D) has been associated with several disorders including autoimmune diseases, like type 1 diabetes mellitus;...
BACKGROUND
Vitamin D deficiency and/or insufficiency (hypovitaminosis D) has been associated with several disorders including autoimmune diseases, like type 1 diabetes mellitus; cardiovascular diseases; neoplasms; obesity; insulin resistance, and type 2 diabetes mellitus. This problem is common in southern European countries, especially in elderly and institutionalized persons. In HIV-infected individuals, hypovitaminosis D has been correlated with various complications like tuberculosis, hyperparathyroidism, bone mass loss, premature atherosclerosis, and systemic arterial hypertension, deterioration of immune function, progression of the disease and overall mortality.
OBJECTIVE
The objective of this study was to examine the prevalence and causes of hypovitaminosis D in a cohort of Greek HIV-infected patients, the factors, and possible complications associated with it.
METHODS
All patients attending our HIV unit for a period of 5 months were included in this study. Vitamin D status, medical anamnes, and laboratory tests were obtained at baseline; patients were followed for 3 years and HIV-related complications were noted. No patient received vitamin D supplementation during the follow-up period.
RESULTS
Hypovitaminosis D was common, with 83.7% of the patients showing levels below 30ng/dl and 55.4% below 20ng/dl. After multivariable analysis, age and duration of treatment were the only significant factors for low vitamin D levels. During follow-up, 26 patients exhibited a total of 34 HIV-related complications, the most common being pneumonocystis jiroveci pneumonia (PCP). Hypovitaminosis D showed a positive correlation with overall complications, PCP as well as wasting syndrome.
CONCLUSION
Overall, our study shows that hypovitaminosis D is common in HIV-infected individuals and should probably be treated as soon as possible to protect these patients from serious HIVrelated complications like PCP or wasting syndrome.
PubMed: 38874038
DOI: 10.2174/011570162X302844240605104855 -
Infection and Drug Resistance 2024The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in...
Clinical Characteristics and Epidemiological Analysis of Pneumocystis Jirovecii Pneumonia Infection in Kidney Transplant Patients with Trimethoprim-Sulfamethoxazole Dose Reduction Prophylaxis Strategy.
BACKGROUND
The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in individuals who have undergone kidney transplantation. Nevertheless, the potential for severe adverse reactions associated with this treatment cannot be overlooked, and the determination of an optimal dosage regimen continues to be a matter of investigation. The current study evaluated the effectiveness of low-dose TMP-SMX for PJP prophylaxis in kidney transplant patients and conducted an analysis of the clinical characteristics and epidemiological trends in patients with PJP infection.
METHODS
This retrospective analysis studied electronic medical records of 1763 kidney transplant recipients from 2017 to 2020. These patients were initially prescribed a daily half-strength TMP-SMX (40 mg/200 mg), and the efficacy of this regimen was assessed during a follow-up period of 3-51 months.
RESULTS
Under our PJP prevention and adjustment strategy, 24 patients were infected with PJP. The overall morbidity of PJP infection in our study was 1.36%, corroborates with findings from previously published studies. Among these 24 patients, up to 87.5% had their dosage adjusted due to increased creatinine or other adverse reactions, the most frequent dose was daily quarter-strength TMP-SMX (20 mg/100 mg). TMP-SMX prophylaxis successfully postponed and distributed the onset of PJP, with the mean duration from transplantation to the occurrence of PJP being 13.50±7.11 months.
CONCLUSION
Daily administration of half-strength TMP-SMX can effectively prevent PJP, and prolonging prophylaxis with this medication may potentially reduce the incidence of infection.
PubMed: 38868399
DOI: 10.2147/IDR.S461206 -
Heliyon Jun 2024We present an AIDS patient coinfected with nontuberculous mycobacteria, and COVID-19, who finally recovered from the coinfection. The 36-year-old man had two...
We present an AIDS patient coinfected with nontuberculous mycobacteria, and COVID-19, who finally recovered from the coinfection. The 36-year-old man had two hospitalizations. In the first hospitalization, the patient was diagnosed with , HIV, and COVID-19 quickly and accurately, and the corresponding treatment worked well. The second hospitalization can be divided into four stages: (1) Persistent fever period; (2) Persistent fever and Pulmonary Progression; (3) ICU period; and (4) Pneumothorax period. During the second hospitalization, the diagnosis of Mycobacterium colombiense was hard because the NGS, acid-fast bacilli, and culture of vomit, sputum, and bronchoalveolar lavage fluid were all negative. Still, we detected acid-fast bacilli in the blood mycobacterium culture. In conclusion, we report a severe pneumonia AIDS patient coinfected with , COVID-19, and Mycobacterium colombiense who finally recovered from the disease. Nontuberculous mycobacteria infection is common in HIV patients, but bronchoalveolar lavage fluid NGS cannot identify nontuberculous mycobacteria in our report. Traditional blood culture was useful in detecting acid-fast bacilli in our study and then detecting the pathogens with NGS. Combining traditional microbial culture and emerging rapid NGS methods is more conducive to clinical diagnosis and treatment.
PubMed: 38867990
DOI: 10.1016/j.heliyon.2024.e31729 -
Chest Jun 2024
Should We Reconsider Pneumocystis Pneumonia Presentation and Treatment According to Its Underlying Disease?: An Unsupervised Cluster Analysis of a Retrospective Multicenter Study.
PubMed: 38866071
DOI: 10.1016/j.chest.2024.04.038 -
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 -
Clinical Infectious Diseases : An... Jun 2024This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different...
BACKGROUND
This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations.
METHODS
A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined.
RESULTS
Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients.
CONCLUSIONS
On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested.
PubMed: 38860786
DOI: 10.1093/cid/ciae239 -
Chest Jun 2024
Topics: Humans; Pneumonia, Pneumocystis
PubMed: 38852956
DOI: 10.1016/j.chest.2024.02.038 -
Microbes and Infection Jun 2024The lung microbiota of patients with pulmonary diseases is disrupted and impacts the immunity. The microbiological and immune landscape of the lungs in patients with...
Integrated analysis of microbiome and host transcriptome unveils correlations between lung microbiota and host immunity in bronchoalveolar lavage fluid of pneumocystis pneumonia patients.
OBJECTIVE
The lung microbiota of patients with pulmonary diseases is disrupted and impacts the immunity. The microbiological and immune landscape of the lungs in patients with pneumocystis pneumonia (PCP) remains poorly understood.
METHODS
Multi-omics analysis and machine learning were performed on bronchoalveolar lavage fluid to explore interaction between the lung microbiota and host immunity in PCP. Then we constructed a diagnostic model using differential genes with LASSO regression and validated by qPCR. The immune infiltration analysis was performed to explore the landscape of lung immunity in patients with PCP.
RESULTS
Patients with PCP showed a low alpha diversity of lung microbiota, accompanied by the elevated abundance of Firmicutes, and the differential expressed genes (DEGs) analysis displayed a downregulation of MAPK signaling. The MAPK10, TGFB1, and EFNA3 indicated a potential to predict PCP (AUC = 0.86). The lung immune landscape in PCP showed the lower levels of naïve CD4 T cells and activated dendritic cells. The correlation analysis of the MAPK signaling pathway-related DEGs and the differential microorganisms at the level of phylum showed that the Firmicutes was negatively correlated with these DEGs.
CONCLUSION
We profiled the characteristics of lung microbiota and immune landscape in PCP, which may contribute to elucidating the mechanism of PCP.
PubMed: 38849069
DOI: 10.1016/j.micinf.2024.105374 -
[Incidence, characteristics and survival of patients with pneumocystis pneumonia in solid oncology].Bulletin Du Cancer Jun 2024Pulmonary pneumocystis causes interstitial lung disease, particularly in patients with solid cancers. The aim of this study is to clarify its incidence, which remains...
INTRODUCTION
Pulmonary pneumocystis causes interstitial lung disease, particularly in patients with solid cancers. The aim of this study is to clarify its incidence, which remains poorly understood, and to identify patients at risk and prognostic factors.
METHODS
Data on patients with solid tumors and pulmonary pneumocystis were retrospectively collected from January 1, 2014 to December 31, 2019 in two hospitals in Rennes. Incidence was estimated via the Poisson model. Survival data were estimated using Kaplan-Meier method and Log-rank test. A multivariate Cox model was performed to identify risk factors for death.
RESULTS
The incidences of pulmonary pneumocystis in metastatic cancer patients receiving parenteral systemic therapy are 198 and 349 cases per 100,000 patients per year in these two centers, respectively. Most patients were being treated with corticosteroids and chemotherapy at the time of pulmonary pneumocystis. The mortality rate for patients with pulmonary pneumocystis is 38%. Median overall survival was 2,7 months. Risk factors for death are corticotherapy greater than 20mg, prednisone equivalent, daily and chemotherapy.
DISCUSSION
Pulmonary pneumocystis pneumonia is rare but not exceptional and has a poor prognosis in solid oncology. It frequently occurs in patients treated with long-term corticosteroids. Oncologists need to be better informed to discuss prophylaxis whenever corticosteroids are prescribed for several weeks.
PubMed: 38845334
DOI: 10.1016/j.bulcan.2024.04.011