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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.

BackgroundThe incidence of secondary pulmonary infections is not well described in hospitalized COVID-19 patients. Understanding the incidence of secondary pulmonary infections and the associated bacterial and fungal microorganisms identified can improve patient outcomes.ObjectiveThis narrative review aims to determine the incidence of secondary bacterial and fungal pulmonary infections in hospitalized COVID-19 patients, and describe the bacterial and fungal microorganisms identified.MethodWe perform a literature search and select articles with confirmed diagnoses of secondary bacterial and fungal pulmonary infections that occur 48 h after admission, using respiratory tract cultures in hospitalized adult COVID-19 patients. We exclude articles involving co-infections defined as infections diagnosed at the time of admission by non-SARS-CoV-2 viruses, bacteria, and fungal microorganisms.ResultsThe incidence of secondary pulmonary infections is low at 16% (4.8–42.8%) for bacterial infections and lower for fungal infections at 6.3% (0.9–33.3%) in hospitalized COVID-19 patients. Secondary pulmonary infections are predominantly seen in critically ill hospitalized COVID-19 patients. The most common bacterial microorganisms identified in the respiratory tract cultures are Pseudomonas aeruginosa, Klebsiella species, Staphylococcus aureus, Escherichia coli, and Stenotrophomonas maltophilia. Aspergillus fumigatus is the most common microorganism identified to cause secondary fungal pulmonary infections. Other rare opportunistic infection reported such as PJP is mostly confined to small case series and case reports. The overall time to diagnose secondary bacterial and fungal pulmonary infections is 10 days (2–21 days) from initial hospitalization and 9 days (4–18 days) after ICU admission. The use of antibiotics is high at 60–100% involving the studies included in our review.ConclusionThe widespread use of empirical antibiotics during the current pandemic may contribute to the development of multidrug-resistant microorganisms, and antimicrobial stewardship programs are required for minimizing and de-escalating antibiotics. Due to the variation in definition across most studies, a large, well-designed study is required to determine the incidence, risk factors, and outcomes of secondary pulmonary infections in hospitalized COVID-19 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.

Background. Empirical antifungal therapy is the standard treatment for persistent or relapsing antibiotic-resistant neutropenic fever. However, overtreatment resulting in increased toxicity and treatment-related cost is a major shortcoming of such therapy. We assessed the feasibility of a \"preemptive\" approach based on the incorporation of sensitive, noninvasive diagnostic tests for consecutive high-risk neutropenic patients who had received fluconazole prophylaxis while avoiding empirical therapy. Methods. A total of 136 treatment episodes for persons who were at risk of acquiring invasive fungal infection (IFI) were screened for the presence of galactomannan with an enzyme immunoassay. A diagnostic evaluation, which included thoracic computed tomography scanning (HRCT) and bronchoscopy with lavage, was performed on the basis of well-defined clinical, radiological, and microbiological criteria. Only seropositive patients and patients with a positive microbiological test result plus supportive radiological findings received liposomal amphotericin B. Results. Neutropenic fever developed in 117 episodes, of which at least 41 episodes (35%) satisfied existing criteria for empirical antifungal therapy. However, our protocol-driven preemptive approach reduced the rate of antifungal use for these episodes from 35% to 7.7% (a 78% reduction) and led to the early initiation of antifungal therapy in 10 episodes (7.3%) that were clinically not suspected of being IFI. No undetected cases of invasive aspergillosis were identified; 1 case of zygomycosis was missed. Breakthrough candidemia was diagnosed by conventional culture techniques and was treated successfully. With use of a preemptive approach, the 12-week survival rate for patients with IFI was 63.6% (it was 63.1% for those with invasive aspergillosis). Conclusion. Preemptive therapy based on enzyme immunoassay and HRCT reduced the exposure to expensive and potentially toxic drugs and offered effective antifungal control, but it failed to detect non-Aspergillus IFI.

Background Mucormycosis has emerged as a rare but frequently fatal invasive fungal disease. Current knowledge on paediatric mucormycosis is based on case reports and small series reported over several decades. Contemporary data on a large cohort of patients is lacking. Methods Two large international registries (Zygomyco.net and FungiScope™) were searched for mucormycosis cases in ≤19 year-old patients. Cases enrolled between 2005 and 2014 were extracted, and dual entries in the two databases merged. Epidemiology, clinical characteristics, diagnostic procedures, therapeutic management and final outcome were recorded and analysed with SPSS v.12. Results Sixty-three unique cases (44 proven and 19 probable) were enrolled from 15 countries (54 in European and 9 in non-European countries). Median age was 13 years [Interquartile Range (IQR) 7.7] with a slight predominance (54.1 %) of females. Underlying conditions were haematological malignancies (46 %), other malignancies (6.3 %), haematopoietic stem cell transplantation (15.9 %), solid organ transplantation, trauma/surgery and diabetes mellitus (4.8 % each) and a variety of other diseases (7.9 %); in 9.5%, no underlying medical condition was found. Neutropenia was recorded in 46 % of the patients. The main sites of infection were lungs (19 %), skin and soft tissues (19 %), paranasal sinus/sino-orbital region (15.8 %) and rhino-cerebral region (7.9 %). Disseminated infection was present in 38.1 %. Mucormycosis diagnosis was based on several combinations of methods; culture combined with histology was performed in 31 cases (49.2 %). Fungal isolates included Rhizopus spp. (39.7 %), Lichtheimia spp . (17.5 %), Mucor spp. (12.7 %), Cunninghamella bertholletiae (6.3 %) and unspecified (23.8 %). Treatment comprised amphotericin B (AmB) monotherapy in 31.7 % or AmB in combination with other antifungals in 47.7 % of the cases, while 14.3 % received no antifungals. Surgery alone was performed in 6.3 %, and combined with antifungal therapy in 47.6 %. Crude mortality at last contact of follow-up was 33.3 %. In regression analysis, disseminated disease and prior haematopoietic stem cell transplantation were associated with increased odds of death, whereas the combination of systemic antifungal therapy with surgery was associated with improved survival. Conclusion Paediatric mucormycosis mainly affects children with malignancies, presents as pulmonary, soft tissue, paranasal sinus or disseminated disease and is highly lethal. Outcome is improved when active antifungal therapy and surgery are combined.

As the global COVID-19 pandemic spreads worldwide, new challenges arise in the clinical landscape. The need for reliable diagnostic methods, treatments and vaccines for COVID-19 is the major worldwide urgency. While these goals are especially important, the growing risk of co-infections is a major threat not only to the health systems but also to patients’ lives. Although there is still not enough published statistical data, co-infections in COVID-19 patients found that a significant number of patients hospitalized with COVID-19 developed secondary systemic mycoses that led to serious complications and even death. This review will discuss some of these important findings with the major aim to warn the population about the high risk of concomitant systemic mycoses in individuals weakened by COVID-19.

Background Talaromyces marneffei is a common travel related fungal disease, primarily found in southern China and frequently affecting HIV-positive patients. Recently, there has been a notable increase in reports of cases in HIV-negative patients, yet few successful treatments for localized pulmonary talaromycosis with respiratory failure have been documented. Case presentation A 50 year-old welder returned from Fujian to Zibo, Shandong Province (northern China) due to fever and respiratory distress, and sought medical attention at our department. The patient collected pathogenic specimens through various methods, and finally sputum culture revealed T. marneffei . After active antifungal treatment and respiratory support, the patient recovered and was discharged from our hospital. Conclusion Infections caused by T. marneffei can manifest as diffuse pulmonary lesions accompanied by respiratory failure. Key factors for successful treatment include thorough tracking of the disease history, acquiring pathogens through multiple methods, and timely antifungal intervention. We must remain vigilant regarding this infection in nonendemic areas.

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.

Certain proteases derived from house dust mites and plants are considered to trigger initiation of allergic airway inflammation by disrupting tight junctions between epithelial cells. It is known that inhalation of proteases such as house dust mite-derived Der p1 and/or papaya-derived papain caused airway eosinophilia in naïve mice and even in Rag -deficient mice that lack acquired immune cells such as T, B and NKT cells. In contrast, little is known regarding the possible involvement of proteases derived from Aspergillus species (fungal-associated proteases; FAP), which are ubiquitous saprophytic fungi in the environment, in the development of allergic airway eosinophilia. Here, we found that inhalation of FAP by naïve mice led to airway eosinophilia that was dependent on protease-activated receptor-2 (PAR2), but not TLR2 and TLR4. Those findings suggest that the protease activity of FAP, but not endotoxins in FAP, are important in the setting. In addition, development of that eosinophilia was mediated by innate immune cells (ILCs) such as innate lymphoid cells, but not by acquired immune cells such as T, B and NKT cells. Whereas IL-33, IL-25 and thymic stromal lymphopoietin (TSLP) are involved in induction of FAP-induced ILC-mediated airway eosinophilia, IL-33—rather than IL-25 and/or TSLP—was critical for the eosinophilia in our model. Our findings improve our understanding of the molecular mechanisms involved in induction of airway inflammation by FAP.

Patients with lung cancer exhibit heightened susceptibility to invasive pulmonary fungal diseases (IPFD) due to malignancy-associated immunosuppression. Current data on the pathogen distribution profile of IPFD in this population remain limited. This study investigated the epidemiological distribution of fungal pathogens causing IPFD in patients with lung cancer, with the aim of guiding clinical management. We conducted a retrospective analysis of consecutive patients with lung cancer treated at the Second Hospital of Shanxi Medical University from June 2019 to May 2024. Patients were included if they had a discharge diagnosis of IPFD, received antifungal therapy, or presented microbiological evidence of fungal infection. All patients were diagnosed according to the 2007 Revised Consensus on Pulmonary Fungal Infections. Demographic, clinical, and laboratory data were collected. Univariate and multivariate logistic regression analyses were employed to identify independent IPFD risk factors. Of 1274 with lung cancer, 92 had proven or probable IPFD. Candida spp. (57.4 %) and Aspergillus spp. (35.3 %) were the predominant pathogens, with sputum (77.94 %), bronchoalveolar lavage fluid (17.65 %), and tissue (4.41 %) as specimen sources. Multivariate analysis identified the following independent risk factors for IPFD with lung cancer: hypertension (OR=5.08; 95 %CI: 1.41–18.28, P = 0.013), chronic respiratory diseases (OR=3.13; 95 %CI: 1.14–8.56, P = 0.026), bone marrow suppression (OR=2.72; 95 % CI: 1.17–6.33, P = 0.020), multiple comorbidities (OR=2.68; 95 % CI: 1.02–7.09, P = 0.046), and smoking (OR=2.47; 95 %CI: 1.08–5.64, P = 0.032). Candida and Aspergillus species were the most common causative agents of IPFD in patients with lung cancer. However, the emergence of less common fungi such as Geotrichum capitatum and Rhizopus microsporus, observed with increasing frequency in this study, warrants heightented clinical vigilance. Recognizing key risk factors, including chronic respiratory diseases, male sex, hypertension, multiple comorbidities and smoking, may guide early diagnosis and targeted antifungal therapy, ultimately improving clinical outcomes. •This study revealed the etiological epidemiological characterisrics of IPFD in lung cancer patients in northern China.•Aspergillus species were predominantly isolated from lung tissue and BALF samples, highlighting the need for empirical antifungal therapy targeting Aspergillus in high-risk lung cancer patients.•We also identified rarely fungi including Neurospora and Rhizopus microsporus, which have not been emphasized in previous studies.•Bone marrow suppression, comorbidities and smoking history were identified as key predisposing factors for IPFD in lung cancer patients.