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Background: Stroke-associated pneumonia (SAP) has been implicated in the morbidity, mortality and increased medical cost after acute ischemic stroke. The annual cost of SAP during hospitalization in the United States approaches USD 459 million. The incidence and prognosis of SAP among intensive care unit (ICU) patients have not been thoroughly investigated. We reviewed the pathophysiology, microbiology, incidence, risk factors, outcomes and prophylaxis of SAP with special attention to ICU studies. Methods: To determine the incidence, risk factors and prognosis of acute SAP, PubMed was searched using the terms ‘pneumonia' AND ‘neurology intensive unit' and the MeSH terms ‘stroke' AND ‘pneumonia'. Non-English literature, case reports and chronic SAP studies were excluded. Studies were classified into 5 categories according to the setting they were performed in: neurological intensive care units (NICUs), medical intensive care units (MICUs), stroke units, mixed studies combining more than one setting or when the settings were not specified and rehabilitation studies. Results: The incidences of SAP in the following settings were: NICUs 4.1-56.6%, MICUs 17-50%, stroke units 3.9-44%, mixed studies 3.9-23.8% and rehabilitation 3.2-11%. The majority of NICU and MICU studies were heterogeneous including different neurovascular diseases, which partly explains the wide range of SAP incidence. The higher incidence in the majority of ICU studies compared to stroke units or acute floor studies is likely explained by the presence of mechanical ventilation, higher stroke severity causing higher rates of aspiration and stroke-induced immunodepression among ICU patients. The short-term mortality of SAP was increased among the mixed and stroke unit studies ranging between 10.1 and 37.3%. SAP was associated with worse functional outcome in the majority of stroke unit and floor studies. Mortality was less consistent among NICU and MICU studies. This difference could be due to the heterogeneity of ICU studies and the effect of small sample size or other independent risk factors for mortality such as the larger neurological deficit, mechanical ventilation, and age, which may simultaneously increase the risk of SAP and mortality confounding the outcomes of SAP itself. The pathophysiology of SAP is likely explained by aspiration combined with stroke-induced immunodepression through complex humeral and neural pathways that include the hypothalamic-pituitary-adrenal axis, parasympathetic and sympathetic systems. Conclusions: A unified definition of SAP, strict inclusion criteria, and the presence of a long-term follow-up need to be applied to the future prospective studies to better identify the incidence and prognosis of SAP, especially among ICU patients.

Background. Acute pulmonary histoplasmosis can be severe, especially following heavy inoculum exposure. Rapid diagnosis is critical and often possible by detection of antigen, but this test may be falsely negative in 17% of such cases. Antibody detection by enzyme immunoassay (EIA) may increase sensitivity and permit the measurement of immunoglobulin M (IgM) and immunoglobulin G (IgG) classes of antibodies separately. Methods. Microplates coated with Histoplasma antigen were used for testing of serum from patients with acute pulmonary histoplasmosis and controls in the MVista Histoplasma antibody EIA. Results for IgG and IgM were reported independently. Results. IgG antibodies were detected in 87.5%, IgM antibodies in 67.5%, and IgG and/or IgM antibodies in 88.8% of patients with acute pulmonary histoplasmosis in this assay, while immunodiffusion, complement fixation, and antigen testing showed sensitivities of 55.0%, 73.1%, and 67.5%, respectively (n = 80). Combining antigen and antibody detection increased the sensitivity to 96.3%. Conclusions. The MVista Histoplasma antibody EIA offers increased sensitivity over current antibody tests while also allowing separate detection of IgG and IgM antibodies and complementing antigen detection. Combining antigen and EIA antibody testing provides an optimal method for diagnosis of acute pulmonary histoplasmosis.

We report 3 cases of probable invasive pulmonary disease caused by Bjerkandera spp. fungi in immunocompromised patients in Germany. Accurate identification required internal transcribed spacer sequencing. Response to antifungal treatment varied. Our report underlines the pathogenic potential of Bjerkandera spp. and the importance of molecular diagnostics in rare fungal infections.

Early diagnosis of invasive mucormycosis is important for timely therapeutic intervention, improved survival, and reduced morbidity. Given the importance of an accurate and rapid diagnosis of invasive mucormycosis to guide the timely initiation of amphotericin B and possible surgical intervention, a coordinated multidisciplinary approach of clinical assessment, diagnostic imaging, and laboratory assessment is necessary. Laboratory assessment for mucormycosis includes the conventional methods of direct examination and culture of tissue, respiratory secretions, bronchoalveolar lavage fluid, and other fluids. However, because conventional diagnostic tools are limited in their sensitivity, advanced molecular amplification systems, antigen detection assays, proteomic profiles, and metabolite detection may complement existing approaches to improve the rate of early diagnosis of invasive mucormycosis.

Background. The sensitivity of the MVista Histoplasma antigen enzyme immunoassay (MiraVista Diagnostics) has been evaluated in disseminated histoplasmosis in patients with AIDS and in the \"epidemic\" form of acute pneumonia. Moreover, there has been no evaluation of the sensitivity of antigenemia detection in disseminated histoplasmosis after the implementation of methods to dissociate immune complexes and denature released antibodies. The goal of this study was to determine the sensitivity of the current antigen assay in different categories of histoplasmosis. Methods. Urine and serum specimens obtained from 218 patients with histoplasmosis and 229 control subjects, including 30 with blastomycosis, were tested. Results. Antigenuria was detected in 91.8% of 158 patients with disseminated histoplasmosis, 83.3% of 6 patients with acute histoplasmosis, 30.4% of 46 patients with subacute histoplasmosis, and 87.5% of 8 patients with chronic pulmonary histoplasmosis; antigenemia was present in 100% of 31 tested cases of disseminated histoplasmosis. Among patients with disseminated cases, antigenuria was detected more often and at higher concentrations in immunocompromised patients and those with severe disease. Specificity was 99.0% for patients with nonfungal infections (n = 130) and in healthy subjects (n = 69), but cross-reactivity occurred in 90% of patients with blastomycosis. Conclusions. The sensitivity of antigen detection in disseminated histoplasmosis is higher in immunocompromised patients than in immunocompetent patients and in patients with more severe illness. The sensitivity for detection of antigenemia is similar to that for antigenuria in disseminated infection.

Histoplasma capsulatum var capsulatum is an endemic respiratory pathogen presenting in various forms including miliary histoplasmosis, acute and chronic pulmonary histoplasmosis, and acute or subacute disseminated disease. The differential diagnosis of chronic pulmonary histoplasmosis (CPH) is broad, encompassing bacterial, fungal and malignant aetiologies. PubMed was searched for relevant articles on the radiological characteristics of CPH and the most common differential diagnoses of tuberculosis and chronic pulmonary aspergillosis. The Fleischner Society Glossary of Terms for Thoracic Imaging was used to analyze the features. The contribution of culture, antibody and antigen and PCR to the diagnosis of CPH is summarized. Cavitation and pulmonary nodules are the most common features of CPH. Pleural effusion, pleural thickening, intrathoracic lymphadenopathy and bronchiectasis are not characteristic of CPH; uncommonly CPH can be complicated by an aspergilloma. Data on the radiologic features of CPH are derived primarily from the USA, Brazil, and China. CPH can be diagnosed by respiratory fungal culture (using extended culture times) or Histoplasma PCR (although data are scarce) and serum Histoplasma antigen and antibody. Data on bronchoscopy sampling for antigen are lacking. In patients with pulmonary cavitation without a confirmed diagnosis of tuberculosis or aspergillosis should be evaluated for CPH.

Purpose Mucormycosis encompasses a group of opportunistic fungal infections caused by Zygomycetes, order Mucorales. Mucormycosis can manifest as rhino-orbito-cerebral, pulmonary, gastrointestinal, cutaneous, and disseminated infections. Pulmonary mucormycosis is the second most common presentation. This manuscript characterizes the demographics, clinical presentation, diagnostic procedures, radiologic findings, therapeutic interventions, and outcome in pulmonary mucormycosis. Methods We retrospectively reviewed clinical data of 35 patients with pulmonary mucormycosis from 2000 to 2015. Microbiologic diagnosis was based on positive culture from a sterile site or findings on histopathology consistent with mucormycosis. Independent predictors of 28-day mortality were assessed using logistic regression. Survival curves were estimated using Kaplan–Meier method. Results There was male predominance with a mean age of 55 ± 15 years. Analysis of predisposing conditions revealed the prevailing presence of malignancy. Sixty-six percent of patients were receiving immunosuppressive agents. Common presenting clinical findings were fever, neutropenia, dyspnea, and cough. Radiologic findings included pleural effusion and nodules. All patients received medical therapy and 43% underwent additional surgical intervention. Twenty eight day mortality was 29% with concurrent bacteremia found as the sole independent predictor. Similar survival from pulmonary mucormycosis was noted over time. Conclusions Pulmonary mucormycosis is an opportunistic angioinvasive fungal infection. Physicians must have a high level of suspicion in immunocompromised patients with fever and respiratory symptoms refractory to antibiotics. A low threshold should be had for performing an invasive procedure to gain reliable diagnosis, as early, aggressive medical and surgical interventions are needed for successful treatment.

Pulmonary histoplasmosis has traditionally been considered geographically restricted to disease-endemic regions. Taiwan, historically nonendemic, has recently witnessed rising infections. We conducted a retrospective study by reviewing adult patients in Taiwan who had pathologically confirmed pulmonary histoplasmosis during June 1997-December 2024. We analyzed 14 cases with lung involvement. Eight case-patients were male and 6 female; mean age was 56.6 years. Of note, 11 case-patients (78.6%) had no history of travel to histoplasmosis-endemic regions; 10 (71.4%) were immunocompetent. Left upper lobe involvement was most common (n = 4 [28.6%]), with nodular lesions predominating (n = 12 [85.7%]). Most (11 [78.6%]) patients received antifungal therapy, mostly with voriconazole. Outcomes were favorable; 1 (7.1%) patient died. Two additional case-patients without lung involvement exhibited similar demographics and clinical outcomes. Case identification rate has increased since 2015. This 27-year study documents the emergence of pulmonary histoplasmosis in Taiwan, emphasizing the need for heightened clinical suspicion in nonendemic regions.

Abstract Coccidioidomycosis is a common cause of community-acquired pneumonia in the southwest United States, Mexico, and South America. The disease has seen a marked increase in incidence in the western United States in the last decade and can be acquired by individuals who travel even briefly through an endemic area, presenting a diagnostic dilemma for clinicians who are not familiar with the disease. The clinical and radiographic manifestations of pulmonary coccidioidomycosis often mimic those of other causes of pneumonia. However, because treatment recommendations and the potential for chronic sequelae of acute infection differ substantially from those for bacterial community-acquired pneumonia, accurate, timely diagnosis of coccidioidomycosis is paramount. A number of diagnostic tests are available with varying sensitivity and specificity, making the approach complex. Radiographic features, although nonspecific, sometimes demonstrate patterns more suggestive of coccidioidomycosis than bacterial community-acquired pneumonias. A routine blood count may reveal eosinophilia. Serologic testing is used most widely but may be negative early in the course of disease, potentially leading to misdiagnosis with subsequent inappropriate treatment and follow-up. The sensitivity of serologic testing is lower in immunocompromised patients, a population at the highest risk for developing severe disease. When clinically appropriate, other biologic specimens, such as sputum, bronchoalveolar lavage fluid, or lung biopsies, may allow for rapid, definitive diagnosis. In light of the significantly increased incidence and complexities in diagnosis of coccidioidomycosis, we examine the diagnostic approach and provide examples of classic clinical and radiographic presentations, discuss the utility of serologic testing, and suggest algorithms that may aid in the diagnosis.

Metagenomic next-generation sequencing (mNGS) is a comprehensive approach for sequence-based identification of pathogenic microbes. However, reports on the use of mNGS in pulmonary infection applied to lung biopsy tissues remain scarce. In this study, we applied mNGS to detect the presence of pathogenic microbes in lung biopsy tissues from 20 patients with pulmonary disorders indicating possible infection. We applied a new data management for identifying pathogen species based on mNGS data. We determined the thresholds for the unique reads and relative abundance required to identify the infectious pathogens. Potential pathogens of pulmonary infections in 15 patients were identified by mNGS. The comparison between mNGS and culture method resulted that the sensitivity and specificity were 100.0% (95% CI: 31.0-100.0%) and 76.5% (95% CI: 49.8-92.2%) for bacteria, 57.1% (95% CI: 20.2-88.2%) and 61.5% (95% CI: 32.2-84.9%) for fungi. The positive predictive value (PPV) (42.9% for bacteria, 44.4% for fungi) was much lower than negative predictive value (NPV) (100% for bacteria, 72.7% for fungi) in mNGS vs. culture method. The mNGS showed the highest specificity (100.0 and 94.1%) and PPV (100.0 and 75.0%) in the evaluation of fungi and MTBC respectively, when compared with histopathology method. The study indicated that mNGS of lung biopsy tissues can be used to detect the presence (or absence) of pulmonary pathogens in patients, with potential benefits in speed and sensitivity. However, accurate data management and interpretation of mNGS are required, and should be combined with observations of clinical manifestations and conventional laboratory-based diagnostic methods.