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American Journal of Health-system... Feb 2024Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat multiple hematologic malignancies and graft-versus-host disease. Though less myelosuppressive than...
PURPOSE
Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat multiple hematologic malignancies and graft-versus-host disease. Though less myelosuppressive than cytotoxic chemotherapy, increased infections, including invasive fungal infections (IFIs), have been reported with ibrutinib use. This study aimed to determine the characteristics and risk factors for infection associated with ibrutinib at our institution.
METHODS
Patients who received ibrutinib between June 2014 and August 2019 were included. Primary endpoints were the incidence of any infection and the incidence of serious infection (defined as hospitalization, parenteral antimicrobial therapy, or pneumonia regardless of hospitalization). Infection risk factors were assessed using logistic regression.
RESULTS
One hundred thirty-two patients were identified (78% male; median age, 71 years). The most common indications for ibrutinib were chronic lymphocytic leukemia (67%) and mantle cell lymphoma (12%). Infection and serious infection occurred in 94 (71%) and 47 (36%) patients, respectively; when pneumonia was excluded as a criterion for serious infection, the serious infection rate was 27%. The median time from ibrutinib initiation to first infection was 125 days. Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT) (odds ratio [OR], 4.60; 95% CI, 1.22-17.4) and corticosteroid use (OR, 5.55; 95% CI, 1.52-20.3) were significant risk factors for serious infection. IFIs were diagnosed in 7 patients (5%): 5 had Pneumocystis jirovecii pneumonia and 2 were infected with invasive molds.
CONCLUSION
Serious infection and IFI rates are high but similar to those previously described. Risk factors for serious infection included allo-HSCT and corticosteroid use. Targeted antimicrobial prophylaxis should be evaluated in prospective studies in patients on ibrutinib to reduce serious infections and IFI.
Topics: Humans; Adult; Male; Aged; Female; Prospective Studies; Leukemia, Lymphocytic, Chronic, B-Cell; Hematologic Neoplasms; Anti-Infective Agents; Pneumonia; Adrenal Cortex Hormones; Adenine; Piperidines
PubMed: 37675967
DOI: 10.1093/ajhp/zxad210 -
BMJ Open Oct 2023We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19. (Review)
Review
OBJECTIVES
We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19.
STUDY DESIGN
Scoping review, using PRISMA-ScR reporting standards. Medline, PubMed, AMED, Embase, CINAHL and LitCovid databases were searched between 16 and 22 February 2021, with studies included from any publication date up to and including the search date.
INTERVENTION
Short exercise tests.
PRIMARY OUTCOME MEASURES
Safe discharge from hospital, readmission rate, length of hospital stay, mortality. Secondary outcomes measures: safety, feasibility and reliability.
RESULTS
Of 1612 original records screened, 19 studies were included in the analysis. These used a variety of exercise tests in patients with chronic obstructive pulmonary disease, suspected pulmonary embolism and pneumocystis carinii pneumonia, heart failure or critical illness. Only six studies had examined patients with COVID-19, of these two were still recruiting to evaluate the 1 min sit-to-stand test and the 40-steps test. There was heterogeneity in patient populations, tests used and outcome measures. Few exercise tests have been validated to support discharge decisions. There is currently no support for short exercise tests for triage of care in patients with COVID-19.
CONCLUSIONS
Further research is needed to aid clinical decision-making at discharge from hospital.
Topics: Humans; COVID-19; Patient Discharge; Exercise Test; Reproducibility of Results; Hospitals
PubMed: 37907292
DOI: 10.1136/bmjopen-2022-068169 -
Microbiology Spectrum Aug 2023Comparison of lung microbiomes between HIV-infected and uninfected patients with pulmonary infection by metagenomic next-generation sequencing (mNGS) has not been...
Comparison of lung microbiomes between HIV-infected and uninfected patients with pulmonary infection by metagenomic next-generation sequencing (mNGS) has not been described in China. The lung microbiomes detected in bronchoalveolar fluid (BALF) by mNGS among HIV-infected and uninfected patients with pulmonary infection were reviewed in the First Hospital of Changsha between January 2019 and June 2022. In total, 476 HIV-infected and 280 uninfected patients with pulmonary infection were enrolled. Compared with HIV-uninfected patients, the proportions of Mycobacterium ( = 0.011), fungi ( < 0.001), and viruses ( < 0.001) were significantly higher in HIV-infected patients. The higher positive rate of Mycobacterium tuberculosis (MTB; = 0.018), higher positive rates of Pneumocystis jirovecii and (all < 0.001), and higher positive rate of cytomegalovirus ( < 0.001) contributed to the increased proportions of Mycobacterium, fungi, and viruses among HIV-infected patients, respectively. The constituent ratios of Streptococcus pneumoniae ( = 0.007) and Tropheryma whipplei ( = 0.002) in the bacteria spectrum were significantly higher, while the constituent ratio of Klebsiella pneumoniae ( = 0.005) was significantly lower in HIV-infected patients than in HIV-uninfected patients. Compared with HIV-uninfected patients, the constituent ratios of and (all < 0.001) in the fungal spectrum were significantly higher, while the constituent ratios of and Aspergillus (all < 0.001) were significantly lower in HIV-infected patients. In comparison to HIV-infected patients without antiretroviral therapy (ART), the proportions of T. whipplei ( = 0.001), MTB ( = 0.024), ( < 0.001), ( < 0.001), and cytomegalovirus ( = 0.008) were significantly lower in HIV-infected patients on ART. Significant differences in lung microbiomes exist between HIV-infected and uninfected patients with pulmonary infection, and ART influences the lung microbiomes among HIV-infected patients with pulmonary infection. A better understanding of lung microorganisms is conducive to early diagnosis and treatment and will improve the prognosis of HIV-infected patients with pulmonary infection. Currently, few studies have systematically described the spectrum of pulmonary infection among HIV-infected patients. This study is the first to provide comprehensive information on the lung microbiomes of HIV-infected patients with pulmonary infection (as assessed by more sensitive metagenomic next-generation sequencing of bronchoalveolar fluid) compared with those from HIV-uninfected patients, which could provide a reference for the etiology of pulmonary infection among HIV-infected patients.
Topics: Humans; Bronchoalveolar Lavage Fluid; Pneumonia; HIV Infections; Microbiota; High-Throughput Nucleotide Sequencing; Metagenomics
PubMed: 37436163
DOI: 10.1128/spectrum.00005-23 -
Annals of the Rheumatic Diseases Feb 2024Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are...
INTRODUCTION
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are not well understood. We aimed to describe serious infectious complications and their potential risk factors.
METHODS
Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry. Episodes of serious infections were described, and their risk factors were analysed using multivariable Cox proportional hazards models.
RESULTS
Seventy-four patients with 133 serious infections were included. The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Microbiological confirmation was obtained in 76%: 52% bacterial, 30% viral, 15% fungal and 3% mycobacterial. Among the pulmonary infections, the main pathogens were 2 (28%), (21%) and (19%). Sixteen per cent of severe infections occurred without any immunosuppressive treatment and with a daily glucocorticoid dose ≤10 mg. In multivariate analysis, age >75 years (HR (95% CI) 1.81 (1.02 to 3.24)), mutation (2.29 (1.10 to 5.10)) and arthralgia (2.14 (1.18 to 3.52)) were associated with the risk of serious infections. JAK inhibitors were most associated with serious infections (3.84 (1.89 to 7.81)) compared with biologics and azacitidine. After a median follow-up of 4.4 (2.5-7.7) years, 27 (36%) patients died, including 15 (56%) due to serious infections.
CONCLUSION
VEXAS syndrome is associated with a high incidence of serious infections, especially in older patients carrying the mutation and treated with JAK inhibitors. The high frequency of atypical infections, especially in patients without treatment, may indicate an intrinsic immunodeficiency.
Topics: Aged; Humans; Arthralgia; Azacitidine; Bacteriophages; Janus Kinase Inhibitors; Mutation; Myelodysplastic Syndromes; Skin Diseases, Genetic; Retrospective Studies
PubMed: 38071510
DOI: 10.1136/ard-2023-224819 -
Ocular Immunology and Inflammation Aug 2023Coronavirus disease 2019 (COVID-19) is associated with immune system dysfunction and makes patients vulnerable to opportunistic infections. This report presents a...
INTRODUCTION
Coronavirus disease 2019 (COVID-19) is associated with immune system dysfunction and makes patients vulnerable to opportunistic infections. This report presents a patient with a history of COVID-19, suffering from opportunistic infections.
CASE DESCRIPTION
We reported a 64-year-old man complaining of progressive visual loss in his left eye, who had previously been hospitalized for three weeks due to COVID-19. In the ophthalmologic assessment, large foci of dense subretinal and intraretinal infiltrations involving the macula were observed (compatible with endogenous fungal endophthalmitis). Real-time PCR result of intraocular fluid was positive for Candida spp. During subsequent hospitalization, the patient also suffered from fever and productive coughs (manifestations of pneumonia caused by Aspergillus fumigatus and ). In response to antibiotic therapy, the fever and coughs subsided, and the ocular examination revealed a dramatic decrease in the size of retinal infiltrations.
CONCLUSIONS
In patients with severe COVID-19, long-term ICU admission and immunosuppressive drugs lead to immune system dysfunction and make the patient more susceptible to opportunistic infections. Consequently, fungal pathogens such as Aspergillus, , and Candida spp. may cause infection in different body organs. Thus, clinicians should be alert and have clinical suspicion to diagnose accurately and manage patients accordingly.
Topics: Male; Humans; Middle Aged; Pneumonia, Pneumocystis; Cough; COVID-19; Aspergillus; Candidiasis; Endophthalmitis; Opportunistic Infections; Eye Infections, Fungal; Candida
PubMed: 36952481
DOI: 10.1080/09273948.2023.2188224 -
Mycopathologia May 2024Pneumocystis pneumonia is a serious lung infection caused by an original ubiquitous fungus with opportunistic behavior, referred to as Pneumocystis jirovecii. P....
Pneumocystis pneumonia is a serious lung infection caused by an original ubiquitous fungus with opportunistic behavior, referred to as Pneumocystis jirovecii. P. jirovecii is the second most common fungal agent among invasive fungal infections after Candida spp. Unfortunately, there is still an inability to culture P. jirovecii in vitro, and so a great impairment to improve knowledge on the pathogenesis of Pneumocystis pneumonia. In this context, animal models have a high value to address complex interplay between Pneumocystis and the components of the host immune system. Here, we propose a protocol for a murine model of Pneumocystis pneumonia. Animals become susceptible to Pneumocystis by acquiring an immunocompromised status induced by iterative administration of steroids within drinking water. Thereafter, the experimental infection is completed by an intranasal challenge with homogenates of mouse lungs containing Pneumocystis murina. The onset of clinical signs occurs within 5 weeks following the infectious challenge and immunosuppression can then be withdrawn. At termination, lungs and bronchoalveolar lavage (BAL) fluids from infected mice are analyzed for fungal load (qPCR) and immune response (flow cytometry and biochemical assays). The model is a useful tool in studies focusing on immune responses initiated after the establishment of Pneumocystis pneumonia.
Topics: Animals; Pneumonia, Pneumocystis; Disease Models, Animal; Bronchoalveolar Lavage Fluid; Lung; Mice; Pneumocystis; Colony Count, Microbial; Pneumocystis carinii; Immunocompromised Host
PubMed: 38709375
DOI: 10.1007/s11046-024-00846-1 -
Cureus Oct 2023Infections caused by ()and ( pneumonia (PJP)) require weight-based dosing for co-trimoxazole. The aim of this study is to assess the appropriateness of co-trimoxazole...
BACKGROUND
Infections caused by ()and ( pneumonia (PJP)) require weight-based dosing for co-trimoxazole. The aim of this study is to assess the appropriateness of co-trimoxazole dosing in adult inpatients for the treatment of these infections.
METHODOLOGY
This is a single-center, cross-sectional study that included adult inpatients treated with co-trimoxazole for a weight-based dose indication ( and PJP). The primary outcome was the appropriateness of co-trimoxazole dosing for these infections.
RESULTS
Forty-three patients were included in the study. Of the 43 patients, 29 (67.4%) were using co-trimoxazole for PJP treatment, and 14 (32.6%) were using it for treatment. The co-trimoxazole dose was appropriate in 22 (51.2%) patients, 21 (72.4%) in the PJP treatment group, and one (7.1%) in the treatment group. Underdosing was observed in 21 (48.8%) patients, of whom eight (27.6%) were in the PJP treatment group and 13 (92.9%) were in the treatment group.
CONCLUSIONS
This study found a relatively high rate of underdosing of co-trimoxazole based on weight in hospitalized adults with PJP and infections.
PubMed: 38022178
DOI: 10.7759/cureus.47400 -
Annales D'endocrinologie May 2024
PubMed: 38724339
DOI: 10.1016/j.ando.2023.08.006 -
Infectious Diseases (London, England) Feb 2024To evaluate the value of nanopore targeted sequencing in diagnosing pneumonia pathogens.
OBJECTIVE
To evaluate the value of nanopore targeted sequencing in diagnosing pneumonia pathogens.
METHODS
This large-scale multicentre prospective study performed in 8 hospitals across China from April to October 2022. Hospitalised patients with a diagnosis of pneumonia at admission were included. Complete clinical data were collected, and bronchoalveolar lavage fluid were obtained from each patient. These samples underwent simultaneous testing using conventional microbial testing, metagenomic next-generation sequencing, and nanopore targeted sequencing.
RESULTS
A total of 218 patients were included. Among the 168 cases of pulmonary infection, 246 strains of pathogens were confirmed. Nanopore targeted sequencing outperformed conventional microbial testing, identifying more pathogens with a sensitivity increase of 47.9% (77.2% vs. 29.3%). Metagenomic next-generation sequencing had a sensitivity of 82.9%. Total of 70.1% patients had consistent results in both metagenomic next-generation sequencing and nanopore targeted sequencing. Nanopore targeted sequencing exhibited significantly higher sensitivity in detecting Pneumocystis jiroveci, cytomegalovirus, Mycobacterium tuberculosis, Nontuberculous mycobacteria, Streptococcus pneumoniae, and Mycoplasma pneumoniae compared to conventional microbial testing. However, metagenomic next-generation sequencing demonstrated higher sensitivity than nanopore targeted sequencing for Aspergillus (88.5% vs. 53.8%). Regarding the detection of co-infections, nanopore targeted sequencing displayed significantly higher sensitivity than conventional microbial testing (76.7% vs. 28.7%) and was on par with metagenomic next-generation sequencing (76.7% vs. 82.9%).
CONCLUSION
Nanopore targeted sequencing performs equally well as metagenomic next-generation sequencing in bronchoalveolar lavage fluid for pathogen diagnosis in pneumonia, both methods showing higher sensitivity than conventional microbial testing. Nanopore targeted sequencing can be considered a reliable method for diagnosing pathogens in pneumonia.
Topics: Humans; Bronchoalveolar Lavage Fluid; Prospective Studies; Nanopores; Pneumonia; Streptococcus pneumoniae; High-Throughput Nucleotide Sequencing; Sensitivity and Specificity
PubMed: 37934028
DOI: 10.1080/23744235.2023.2276785 -
Cureus Aug 2023Histoplasmosis is a fungal infection that, if left untreated, can result in very serious health outcomes, especially in patient populations that are immunocompromised....
Histoplasmosis is a fungal infection that, if left untreated, can result in very serious health outcomes, especially in patient populations that are immunocompromised. While the manifestations of the disease are very diverse and highly dependent on the individual health conditions of the patient, in severe cases, it can lead to serious pneumonia, acute respiratory distress syndrome, and death if rapid medical intervention is not performed. Here, we present the case of a patient with acquired immunodeficiency syndrome who suffered from histoplasmosis pneumonia with suspected superimposed pneumonia. The patient rapidly decompensated shortly after admission to the hospital; he presented just one week after being discharged of a similar infection. After being transferred to the intensive care unit (ICU), aggressive intervention stabilized the patient's condition enough for him to be discharged several days later. We hope the unique circumstances of this patient's hospital stay can guide clinicians in managing serious infections in immunocompromised patients.
PubMed: 37692718
DOI: 10.7759/cureus.43152