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Breakthrough invasive mold infections (IMIs) that occur during posaconazole or voriconazole prophylaxis are rare complications for which epidemiological data are lacking. This retrospective analysis comparing 24 microbiologically documented breakthrough with 66 nonbreakthrough IMIs shows a shift towards non-Aspergillus molds with a significantly increased proportion of rare multidrug-resistant molds.

Abstract Background Lung transplant recipients commonly develop invasive fungal infections (IFIs), but the most effective strategies to prevent IFIs following lung transplantation are not known. Methods We prospectively collected clinical data on all patients who underwent lung transplantation at a tertiary care academic hospital from January 2007–October 2014. Standard antifungal prophylaxis consisted of aerosolized amphotericin B lipid complex during the transplant hospitalization. For the first 180 days after transplant, we analyzed prevalence rates and timing of IFIs, risk factors for IFIs, and data from IFIs that broke through prophylaxis. Results In total, 156 of 815 lung transplant recipients developed IFIs (prevalence rate, 19.1 IFIs per 100 surgeries, 95% confidence interval [CI] 16.4–21.8%). The prevalence rate of invasive candidiasis (IC) was 11.4% (95% CI 9.2–13.6%), and the rate of non-Candida IFIs was 8.8% (95% CI 6.9–10.8%). First episodes of IC occurred a median of 31 days (interquartile range [IQR] 16–56 days) after transplant, while non-Candida IFIs occurred later, at a median of 86 days (IQR 40–121 days) after transplant. Of 169 IFI episodes, 121 (72%) occurred in the absence of recent antifungal prophylaxis; however, IC and non-Candida breakthrough IFIs were observed, most often representing failures of micafungin (n = 16) and aerosolized amphotericin B (n = 24) prophylaxis, respectively. Conclusions Lung transplant recipients at our hospital had high rates of IFIs, despite receiving prophylaxis with aerosolized amphotericin B lipid complex during the transplant hospitalization. These data suggest benefit in providing systemic antifungal prophylaxis targeting Candida for up to 90 days after transplant and extending mold-active prophylaxis for up to 180 days after surgery. Lung transplant recipients experienced high rates of invasive fungal infection, despite receiving prophylaxis with aerosolized amphotericin B lipid complex during the transplant hospitalization. Antifungal prophylaxis after lung transplantation should include coverage for invasive candidiasis and prolonged prophylaxis against respiratory molds.

Critically ill patients and patients with haematological cancer are HIV-negative populations at high risk of invasive fungal infections. In intensive-care units, candidaemia and intra-abdominal candidiasis predominate, but aspergillosis has emerged as a lethal, under-recognised cause of pneumonia. In patients with haematological malignancies or who have undergone stem-cell transplantations, pulmonary disease due to aspergillus and other mould diseases predominate. In this Series paper, we provide an update on risk assessment, new diagnostic strategies, and therapeutic approaches. New concepts have emerged for use of risk prediction rules and an evidence base now exists for inclusion of biomarkers (eg, galactomannan, 1,3-β-D-glucan, and PCR assays for Aspergillus spp) into early diagnostic and therapeutic strategies. Imaging techniques remain helpful for early diagnosis of pulmonary mould diseases, with PET techniques offering potential improvements in diagnostic specificity and evaluation of clinical response. Echinocandins and triazoles have been validated extensively for prophylaxis, empirical therapy, and targeted therapy, but an increase in intrinsically resistant fungi and emergence of secondary resistance as a result of drug-induced selection pressure are of major concern. Echinocandins remain a major component of treatment of invasive candidiasis and new triazoles are the best alternative for prophylaxis and therapy of invasive aspergillosis.

Opportunistic infections caused by Pneumocystis jirovecii, Cryptococcus neoformans, and ubiquitous airborne filamentous fungi have been recently reported in patients with hematological cancers historically considered at low risk for invasive fungal infections (IFIs), after receipt of the Bruton tyrosine kinase inhibitor ibrutinib. The spectrum and severity of IFIs often observed in these patients implies the presence of a complex immunodeficiency that may not be solely attributed to mere inhibition of Bruton tyrosine kinase. In view of the surge in development of small molecule kinase inhibitors for treatment of malignant and autoimmune diseases, it is possible that there would be an emergence of IFIs associated with the effects of these molecules on the immune system. Preclinical assessment of the immunosuppressive effects of kinase inhibitors and human studies aimed at improving patient risk stratification for development of IFIs could lead to prevention, earlier diagnosis, and better outcomes in affected patients.

Invasive fungal infections (IFIs) are life-threatening complications in immunocompromised patients, particularly those with hematologic malignancies or undergoing transplantation. Despite advances in diagnostic methods and antifungal therapy, IFI-related mortality remains unacceptably high. Evidence from Latin America is scarce, limiting the understanding of regional epidemiology and outcomes. Our work aimed to analyze the epidemiological and clinical profiles of pediatric hemato-oncologic patients diagnosed with proven IFIs. We conducted a retrospective, cross-sectional study by reviewing medical records of patients diagnosed with proven IFIs according to the 2020 criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group, at the Hospital Universitario “Dr. José Eleuterio González” in northeast Mexico, between 2018 and 2024. Statistical analysis included descriptive and inferential methods. A p-value < 0.05 was considered statistically significant. Thirty-three patients were included (mean age 6 years; 54.5% male). Most (91%) were classified as high risk for IFIs, and acute lymphoblastic leukemia was the most frequent underlying malignancy (72.7%). Mold infections accounted for 69.7% of cases, mainly Aspergillus spp. and Fusarium spp. , while Candida tropicalis was the most common yeast. The sinonasal region was the predominant site of mold disease. Prophylaxis was administered in 69.7% of patients, most commonly with itraconazole. Amphotericin B was the primary therapeutic agent, alone or in combination with voriconazole, and 42.4% required surgical intervention. Overall mortality was 21.2%, higher in yeast infections (30%) compared with molds (17.4%). Intensive care unit admission was the only independent predictor of death (OR 35.4; p =  0.019). In pediatric hemato-oncologic patients, IFIs were predominantly associated with acute lymphoblastic leukemia, neutropenia, and induction chemotherapy. Mold infections accounted for most cases, and mortality remained high despite prophylaxis. These findings provide novel data from Latin America, where studies on pediatric IFIs are limited, and underscore the need for improved diagnostic and preventive strategies in high-risk populations.

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.

Invasive mold diseases (IMDs) are a severe complication of immunocompromised subjects and an emerging problem among severely ill, apparently immunocompetent patients. The aim of this study was to describe the epidemiological and clinical features of IMDs in Chile. Prospective study of IMD cases in children and adults from 11 reference hospitals in Chile from May 2019 to May 2021. One hundred seventy-six cases were included, 135 in adults and 41 in children, with an overall incidence of 0.4/1,000 admissions. The median age was 10.5 years in children and 56.6 years in adults, with male gender predominance in adults (61.5% versus 41.5%, p = 0.03). Immunosuppression was the most common condition in both children and adults. However, cancer, neutropenia, and hematopoietic cell transplantation were significantly more frequent in the pediatric group. In contrast, diabetes, viral pneumonia, chronic kidney disease, and chronic obstructive pulmonary disease were significantly more frequent among adult patients. Regarding the diagnostic category, 30.1% of cases were proven, 55.7% probable and 14.2% possible. Aspergillosis was the most frequent IMD diagnosed in 75.5% of cases, followed by fusariosis in children and mucormycosis in adults. Viral pneumonia was associated in 40.3% of cases, mainly COVID-19, with aspergillosis in 87.3%. No triazole resistance was observed in Aspergillus spp.. Antifungals were prescribed in 97.2% of the patients: voriconazole 61.4%, liposomal amphotericin 20.5%, combination antifungals 11.1%, and others 6.4%. Overall survival was 68.7%, 61.4%, and 51.7% at 30, 90 and 180 days, respectively. This is the most extensive study of IMDs in Chile, evidencing an incidence of 0.4 per 1,000 admissions, with aspergillosis being the most frequent infection. Nearly 40% of cases were associated with respiratory viruses, accounting for the impact of COVID-19. Despite almost all patients starting antifungal therapy, the survival rate was poor. It is advisable to start a surveillance program of IMDs in Chile and verify the absence of azole resistance of Aspergillus spp.

Background Non- Aspergillus invasive fungal infections (NAFI) are increasingly reported in patients with Chronic Granulomatous Disease (CGD), but precise clinical descriptions remain scarce. Objective and Methods We conducted a retrospective analysis of NAFI cases among CGD patients in the French National Registry of Primary Immunodeficiencies (CEREDIH) and in a comprehensive literature review. Results We identified 16 proven NAFI (9 molds, 6 yeasts and 1 Pneumocystis ) among 263 CGD patients from CEREDIH and included an additional 106 probable/proven NAFI from a literature review (75 molds, 29 yeasts, 1 Pneumocystis, 1 dimorphic ). Mold NAFI occurred at a median age of 17 years [IQR 9–23], and were mostly located to the lungs (79%, 65/82). Mold NAFI were breakthrough in 59% of patients (35/59), and 24% were receiving immunosuppressive treatments (13/54, mostly high-dose corticosteroids, n = 11). Lung surgical biopsies yielded the highest diagnostic rate (39/39) compared to less invasive methods (BAL 8/18 and transthoracic punctures 8/12). Nine patients with mold NAFI, including 3 refractory cases, were cured after Hematopoietic Stem Cell Transplantation (HSCT). Overall mortality for mold NAFI was 25% (20/81). Yeast infections occurred at a median age of 5 years [IQR 0–13], and 36% were receiving immunosuppressive treatments (5/14, mostly anti-TNF agents, n = 4). Infections were frequently located to lymph nodes or lungs, and 64% (21/33) were disseminated. Two yeast NAFI were cured after HSCT. Mortality was 26% (7/27). Conclusion NAFI in CGD patients are frequently severe, often occur despite prophylaxis and under additional immunosuppression, commonly require invasive procedures for diagnosis, and may be effectively managed with HSCT.

Invasive fungal infections (IFIs) are a leading cause of morbidity and attributable mortality in oncohematologic patients. Timely diagnosis is essential but challenging. Herein we retrospectively describe 221 cases of antifungal treatments (AFT) administered in a monocentric real-life cohort of hematological malignancies. Between January 2010 and July 2017, 196 oncohematologic patients were treated with AFT at our Hematology Department. Diagnosis of IFIs was carried out according to EORTC/MSG-2008 guidelines.The most represented disease was acute myeloid leukemia (104 patients). Median age was 61 years; at fever onset 177 (80%) patients had a neutrophil count<0.5x109/L. Twenty-nine (13%) patients were receiving antifungal prophylaxis (26 posaconazole, 2 fluconazole, 1 itraconazole). The incidence of AFT was 13%. Serum galactomannan antigen (GM) was positive in 20% of the tested cases, while 85% of the patients had a CT scan suggestive for IFI. Twenty-one percent of these cases had a GM positive. Sixty-five out of 196 patients (33%) showed positive culture results, in particular Candida spp. were identified in 45 isolates, while Aspergillus spp. in 16 cases. Fourteen patients presented multiple positivity. Twenty-two (10%) cases were classified as proven IFIs, 61 (28%) as probable and 81 (37%) as possible, but 57 (26%) cases could not be classified. Fifty-nine percent of the patients received single agent AFT, 37% sequential AFT, 8% a combination regimen. Liposomal-amphotericin-B was the most used AFT. IFIs attributable mortality was 20%. This epidemiologic survey underlined a persistent significant use of AFT and a high mortality rate of IFIs. We suggest that further powerful diagnostic approaches should be investigated to improve the diagnostic accuracy and potential therapeutic implication.

During the last two decades, wound invasive fungal diseases (WIFDs) have reemerged as important causes of mortality and morbidity in military personnel and civilian casualties in war areas. Historically, mycotic infections acquired in combat operations during Vietnam War and were associated with burn wounds. Modern combat related WIFDs are almost exclusively associated with severe traumatic events which encompass blast exposure as the primary mechanism of injury and subsequent extremity amputation and extensive blood loss. Such infections often lead to deep tissue necrosis, long hospitalizations, extensive surgeries, and more severe amputation. Studies of combat related WIFDs among U.S. military personnel in Operation Enduring Freedom (Afghanistan) demonstrated incidence rates of approximately 7% and crude mortality of 8.5%. WIFDs were also seen in U.K. military personnel returning from Afghanistan and are common in the current Ukraine and Gaza conflicts. Mucorales , Aspergillus and Fusarium species are the predominant causes of WIFDs. These molds are opportunistic pathogens which thrive in patients with immune system imbalances following traumatic injury. They are ubiquitous environmental fungi found in a variety of soils but there are significant regional differences depending on the local soil type, vegetation, and climate. The management of WIFDs is complicated by the limited efficacy of current antifungals on many of these environmental species and by emerging antifungal resistance globally. This review provides an overview of the global burden, epidemiology, and clinical features of combat-related fungal infections with the aim to provide a better understanding of the threat posed for wounded Service Members and civilians.