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Background. Invasive pulmonary aspergillosis (IPA) is a significant problem in patients with chemotherapy-induced prolonged neutropenia. Because pulmonary deposition of conidia is the first step in developing IPA, we hypothesized that inhalation of liposomal amphotericin B would prevent IPA. Methods. We performed a randomized, placebo-controlled trial of patients with hematologic disease with expected neutropenia for ⩾10 days. Patients were randomized to receive liposomal amphotericin B or placebo inhalation twice a week, using an adaptive aerosol delivery system, until neutrophil counts increased to >300 cells/mm3. In subsequent neutropenic episodes, the assigned treatment was restarted. The primary end point was the occurrence of IPA according to European Organization for Research and the Treatment of Cancer-Mycoses Study Group definitions. Kaplan-Meier curves were compared with log-rank tests for intent-to-treat and on-treatment populations. Results. A total of 271 patients were studied during 407 neutropenic episodes. According to the intent-to-treat analysis, 18 of 132 patients in the placebo group developed IPA versus 6 of 139 patients in the liposomal amphotericin B group (odds ratio, 0.26; 95% confidence interval, 0.09–0.72; P=.005). According to the on-treatment analysis, 13 of 97 patients receiving placebo versus 2 of 91 receiving liposomal amphotericin B developed IPA (odds ratio, 0.14; 95% confidence interval, 0.02–0.66; P=.007). Some adverse effects, but none serious, in the liposomal amphotericin B group were reported, most frequently coughing (16 patients vs. 1 patient; P=.002). Conclusion. In high-risk patients, prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of IPA.

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.

Abstract Invasive fungal disease (IFD) during neutropenia goes along with a high mortality for patients after allogeneic hematopoietic cell transplantation (alloHCT). Low-dose computed tomography (CT) thorax shows good sensitivity for the diagnosis of IFD with low radiation exposure. The aim of our study was to evaluate sequential CT thorax scans at two time points as a new reliable method to detect IFD during neutropenia after alloHCT. We performed a retrospective single-center observational study in 265/354 screened patients admitted for alloHCT from June 2015 to August 2019. All were examined by a low-dose CT thorax scan at admission (CT t0) and after stable neutrophil recovery (CT t1) to determine the incidences of IFD. Furthermore, antifungal prophylaxis medications were recorded and cohorts were analyzed for statistical differences in IFD incidence using the sequential CT scans. In addition, IFD cases were classified according to EORTC 2008. At CT t0 in 9.6% of the patients, an IFD was detected and antifungal therapy initiated. The cumulative incidence of IFD in CT t1 in our department was 14%. The use of Aspergillus-effective prophylaxis through voriconazole or posaconazole decreased CT thorax t1 suggesting IFD is statistically significant compared to prophylaxis with fluconazole (5.6% asp-azol group vs 16.3% fluconazole group, p = 0.048). In 86%, CT t1 was negative for IFD. Low-dose sequential CT thorax scans are a valuable tool to detect pulmonary IFDs and guide antifungal prophylaxis and therapies. Furthermore, a negative CT t1 scan shows a benefit by allowing discontinuation of antifungal medication sparing patients from drug interactions and side effects.

Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals.

biologics have significantly advanced the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). However, real-world data regarding the risks of pulmonary fungal infections (PFI) associated with different biologics are limited. Our study aimed to explore PFI incidence among approved biologics, drawing on sources of real-world evidence. We conducted a disproportionality analysis to evaluate the association between biologics and PFI using data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) (2004-2024). We analyzed clinical features, co-occurring adverse events (AEs), time-to-onset (TTO). Our analysis included 3,695 patients who developed PFI following treatment with biologics. The study comprised 28.5% females, 28.6% males, and 42.9% with unspecified gender. The median age was 63 years (interquartile range [IQR] 52-71). Several biologics were associated with elevated PFI risk. Among them, the highest reporting odds ratio (ROR) were observed for infliximab(ROR = 26.02, 95% CI 17.72-38.21), rituximab(ROR = 16.23, 95% CI 13.06-20.18), tocilizumab(ROR = 14.45, 95% CI 12.28-17.00), and baricitinib(ROR = 11.01, 95% CI 7.77-15.59). Other biologics associated with a disproportionality signal in PFI risk included golimumab(ROR = 6.73, 95% CI 2.15-21.13), upadacitinib(ROR = 4.61, 95% CI 2.61-8.14), ustekinumab(ROR = 4.58, 95% CI 1.46-14.36), adalimumab(ROR = 3.45, 95% CI 2.08-5.72), tofacitinib(ROR = 3.18, 95% CI 2.04-4.95), abatacept(ROR = 3.16, 95% CI 1.74-5.73), etanercept(ROR = 2.58, 95% CI 2.06-3.24), certolizumab pegol(ROR = 1.64, 95% CI 1.27-2.10). The signal for secukinumab was not statistically (ROR = 1.70, 95% CI 0.55-5.32). Female was associated with an elevated risk of PFI and fatal outcomes in the logistic regression analysis. Tocilizumab and baricitinib showed a disproportionality signal for fatal outcomes. Our analysis suggested a trend of more pronounced PFI risk signals in elderly patients. TTO analysis demonstrated no significant gender-based differences. However, significant intergroup differences were observed between patients aged 45-64 years and those aged 65-74 years. Notably, TTO profiles varied substantially among biologics, ranging from 30 days (tocilizumab) to 393 days (etanercept). Our findings suggest that concomitant use of biologics is associated with a stronger disproportionality signal for PFI. The inherent limitations and potential reporting biases of the FAERS database necessitate confirmation through large-scale, prospective clinical studies.

Background Previous studies report variation in the incidence of pulmonary fungal infection rates and associated factors in lung cancer patients. This meta‐analysis aimed to provide a comprehensive synthesis of Chinese‐ and English‐language studies to investigate the incidence of pulmonary fungal infections and their associated factors in these patients. Methods Studies reporting the incidence of pulmonary fungal infections or their associated factors in lung cancer patients were systematically searched in the WanFang, CNKI, EMBASE, SinoMed, Web of Science, and PubMed databases until April 2025. Results In total, 37 studies involving 26 841 lung cancer patients were included. The pooled pulmonary fungal infection rate (95% confidence interval) was 14.00% (12.54%–15.45%) in lung cancer patients. Age ≥ 60 years (odds ratio (OR) = 1.85, p = 0.020), male sex (OR = 1.23, p = 0.019), smoking history (OR = 2.24, p < 0.001), chronic obstructive pulmonary disease (OR = 2.19, p = 0.010), interstitial lung disease (OR = 4.40, p < 0.001), diabetes (OR = 2.31, p < 0.001), anemia (OR = 6.47, p = 0.016), small cell lung cancer (OR = 1.46, p = 0.011), squamous cell carcinoma (OR = 1.38, p = 0.001), tumor stages of III–IV (OR = 2.38, p < 0.001), invasive operation (OR = 3.73, p < 0.001), chemotherapy (OR = 1.64, p = 0.011), chemotherapy cycle > 2 (OR = 2.87, p < 0.001), radiotherapy (OR = 1.67, p = 0.001), chemoradiotherapy (OR = 2.72, p < 0.001), surgery (OR = 1.64, p < 0.001), long‐term use of antibiotics (OR = 5.64, p = 0.002), use of glucocorticoid (OR = 4.44, p < 0.001), and hospital stays ≥ 14 days (OR = 3.97, p = 0.006) were linked with higher pulmonary fungal infection risk. Conclusion The pulmonary fungal infection rate (95% CI) was 14.00% (12.54%, 15.45%) in lung cancer patients. Furthermore, the associated factors might help screen for and intervene early in pulmonary fungal infections in patients with lung cancer. This study aimed to estimate the incidence and risk factors of pulmonary fungal infections in lung cancer patients through a meta‐analysis of Chinese and English studies (up to April 2025). The findings indicated that: (1) Incidence: 14.0% (95% CI, 12.54%–15.45%); (2) Major Risk Factors: (a) Demographic: Age ≥ 60 years, male, smoking history. (b) Comorbidities: COPD, interstitial lung disease, diabetes, anemia; (c) Cancer‐related: Small cell or squamous carcinoma, stages III–IV; (d) Treatment‐related: Invasive procedures, chemotherapy (> 2 cycles), radiotherapy, surgery, glucocorticoids, long‐term antibiotics; (e) Hospitalization: ≥ 14 days.

Early non-infectious pulmonary complications represent a significant cause of mortality after hematopoietic cell transplantation (HCT). We tested the hypothesis that oral beclomethasone dipropionate (BDP) is effective for preventing early non-infectious pulmonary complications after allogeneic HCT. We retrospectively reviewed the medical records of 120 patients, 60 in each treatment arm, to identify non-infectious and infectious pulmonary events and pulmonary function test results from all patients who participated in two randomized trials of oral BDP for treatment of acute gastrointestinal GVHD. 17-Beclomethasone monopropionate (17-BMP), the active metabolite of BDP, was evaluated in blood from the right atrium in four patients. Thirty-three of 42 (79%) placebo-treated patients experienced a decrease of the DL CO from pretransplant to day 80 after transplant, compared with 27 of 49 (55%) BDP-treated patients ( P =0.02). In the first 200 days after randomization, there were no cases of non-infectious pulmonary complications in BDP-treated patients, vs four cases among placebo-treated patients ( P =0.04). Levels of 17-BMP were detected in atrial blood at steady state. Delivery of a potent glucocorticoid such as 17-BMP to the pulmonary artery after oral dosing of BDP may be useful in modulating pulmonary inflammation and preventing the development of non-infectious pulmonary complications after allogeneic HCT.

An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Clinical, microbiological and laboratory data of 161 patients aged 6-59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13-32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955-0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009-0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873-98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518-93.0705, p<0.05). Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp.