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Current Opinion in Pulmonary Medicine May 2024This review highlights the epidemiology, pathogenesis and clinical management of pulmonary infections caused by emerging fungal organisms. (Review)
Review
PURPOSE OF REVIEW
This review highlights the epidemiology, pathogenesis and clinical management of pulmonary infections caused by emerging fungal organisms.
RECENT FINDINGS
Emerging fungal infections have arisen as a result of population and environmental changes. An enlarging pool of immunocompromised hosts on triazole antifungal prophylaxis has led to an increased incidence of non- Aspergillus molds, such as Fusarium , Scedosporium and Lomentospora spp. Advances in diagnostic capabilities led to the identification of the Emergomyces genus and non- dermatitidis Blastomyces species, which have a significant disease burden in Africa and the Middle East. Climate change has contributed to changing the distribution of previously confined endemic mycoses, like coccidioidomycosis and talaromycosis. These emerging organisms pose important diagnostic and therapeutic challenges.
SUMMARY
Newly recognized pathogenic fungi and established endemic mycoses with expanding geographic boundaries have become important agents of pulmonary disease. There is a dearth of clinical evidence on the appropriate management of these infections.
Topics: Humans; Mycoses; Fungi; Antifungal Agents; Pneumonia; Lung
PubMed: 38411158
DOI: 10.1097/MCP.0000000000001059 -
Cornea Jun 2022To ascertain the clinicomicrobiological correlation and evaluate the prognostic factors associated with medical resolution in cases of Curvularia, Alternaria, and...
PURPOSE
To ascertain the clinicomicrobiological correlation and evaluate the prognostic factors associated with medical resolution in cases of Curvularia, Alternaria, and Scedosporium keratitis.
METHODS
A retrospective review of clinical and microbiological records of culture-proven cases of Curvularia, Alternaria, and Scedosporium keratitis from 2017 to 2019 was performed. Multivariate logistic regression analyses were performed to assess the predictive factors for medical resolution.
RESULTS
There were a total of 79 eyes of 79 patients. Among these, there were 56 (70.8%), 15 (18.9%), and 8 (10.1%) patients with Curvularia, Scedosporium, and Alternaria keratitis, respectively. Clinical resolution with medical treatment was achieved in 46 of 56 (82.1%) patients with Curvularia keratitis, 8 of 15 (53.3%) patients with Scedosporium, and 7 of 8 (87.5%) patients with Alternaria keratitis. In comparison between Curvularia and Scedosporium, macroscopic pigmentation [18/56 (32.1%)] of anterior stromal plaque-like infiltrate [20/56 (35.7%)] was clinically more in cases with Curvularia, whereas larger diameter of the infiltrate, P = 0.002, posterior stromal infiltrate (40%), P = 0.03, and hypopyon, P = 0.009, were more common with Scedosporium. Multivariate logistic regression analysis, by backward elimination, showed that maximum dimension of the infiltrate (P = 0.01; odds ratio = 0.52, 95% confidence interval, 0.31-0.86) and presence of a hypopyon (P = 0.02; odds ratio = 0.12, 95% confidence interval, 0.02-0.71) were significant factors that were not favoring medical resolution.
CONCLUSIONS
Larger size of the infiltrate, posterior stromal involvement, and presence of a hypopyon are poor prognostic indicators among all 3 species. Variation in species is not a predictor of clinical resolution.
Topics: Corneal Ulcer; Eye Infections, Fungal; Humans; Keratitis; Retrospective Studies; Scedosporium
PubMed: 34369394
DOI: 10.1097/ICO.0000000000002825 -
Journal of Fungi (Basel, Switzerland) Jan 2021Infections caused by the opportunistic pathogens / are on the rise. This causes problems in the clinic due to the difficulty in diagnosing and treating them. This review... (Review)
Review
Infections caused by the opportunistic pathogens / are on the rise. This causes problems in the clinic due to the difficulty in diagnosing and treating them. This review collates information published on immune response against these fungi, since an understanding of the mechanisms involved is of great interest in developing more effective strategies against them. / cell wall components, including peptidorhamnomannans (PRMs), α-glucans and glucosylceramides, are important immune response activators following their recognition by TLR2, TLR4 and Dectin-1 and through receptors that are yet unknown. After recognition, cytokine synthesis and antifungal activity of different phagocytes and epithelial cells is species-specific, highlighting the poor response by microglial cells against . Moreover, a great number of / antigens have been identified, most notably catalase, PRM and Hsp70 for their potential medical applicability. Against host immune response, these fungi contain evasion mechanisms, inducing host non-protective response, masking fungal molecular patterns, destructing host defense proteins and decreasing oxidative killing. In conclusion, although many advances have been made, many aspects remain to be elucidated and more research is necessary to shed light on the immune response to /.
PubMed: 33499053
DOI: 10.3390/jof7020075 -
Transplant Infectious Disease : An... Nov 2023Invasive fungal infections cause significant morbidity and mortality in hematopoietic stem cell transplant recipients. In order to minimize these infections, prophylaxis... (Review)
Review
Invasive fungal infections cause significant morbidity and mortality in hematopoietic stem cell transplant recipients. In order to minimize these infections, prophylaxis has become routine, although the agents used have changed over time. This presents new challenges as we consider an approach to breakthrough infections and recognize the epidemiologic shift toward isolates with higher rates of drug resistance. This review outlines the management of the most common pathogens (Candida, Aspergillus, Mucorales) as well as rarer pathogens that have higher rates of resistance (Trichosporon, Fusarium, Scedosporium, and Lomentospora). We discuss potential approaches to proven or possible breakthrough infections with yeast and pulmonary mold disease. Finally, we outline the role for combination therapy and newer antifungals, acknowledging current knowledge gaps and areas for future exploration.
Topics: Humans; Antifungal Agents; Invasive Fungal Infections; Stem Cell Transplantation; Fusarium; Ascomycota
PubMed: 37864814
DOI: 10.1111/tid.14175 -
Emerging Infectious Diseases Jun 2024Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously... (Observational Study)
Observational Study Review
Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously conducted reported frequent fungal vascular involvement, including aortitis and peripheral arteritis. For this article, we reviewed 7 cases of Scedosporium spp. and L. prolificans arteritis from the Scedosporiosis/lomentosporiosis Observational Study and 13 cases from published literature. Underlying immunosuppression was reported in 70% (14/20) of case-patients, mainly those who had solid organ transplants (10/14). Osteoarticular localization of infection was observed in 50% (10/20) of cases; infections were frequently (7/10) contiguous with vascular infection sites. Scedosporium spp./Lomentospora prolificans infections were diagnosed in 9 of 20 patients ≈3 months after completing treatment for nonvascular scedosporiosis/lomentosporiosis. Aneurysms were found in 8/11 aortitis and 6/10 peripheral arteritis cases. Invasive fungal disease--related deaths were high (12/18 [67%]). The vascular tropism of Scedosporium spp. and L. prolificans indicates vascular imaging, such as computed tomography angiography, is needed to manage infections, especially for osteoarticular locations.
Topics: Humans; Scedosporium; France; Male; Middle Aged; Aged; Female; Mycoses; Adult; Antifungal Agents; Aged, 80 and over; Invasive Fungal Infections
PubMed: 38781681
DOI: 10.3201/eid3006.231409 -
Transplant Infectious Disease : An... Jun 2021Scedosporium apiospermum and Lomentospora prolificans (Scedosporium/Lomentospora) species are emerging, multi-resistant pathogens that cause life-threatening illnesses...
INTRODUCTION
Scedosporium apiospermum and Lomentospora prolificans (Scedosporium/Lomentospora) species are emerging, multi-resistant pathogens that cause life-threatening illnesses among lung transplant (LTx) recipients. The current epidemiology and management in LTx are unknown.
METHODS
We performed a retrospective single center audit of all sputum/bronchoscopy samples for Scedosporium/Lomentospora species in LTx patients over a 24-year period (1995-2019). Patients were diagnosed as colonized or with invasive fungal disease.
RESULTS
From a cohort of 962 LTx recipients, 30 patients (3.1%) cultured Scedosporium/Lomentospora (1.2%, 1.9%, respectively). There were no isolates from 1995 to 2013, with multiple yearly isolates thereafter. Nineteen (63%) cases were classified as IFD, and 11 (37%) as colonization. The median time to first culture from transplantation was 929 days (Interquartile-range [IQR] 263-2960). Most patients (63%) had received antifungals prior to the first positive culture of Scedosporium/Lomentospora for other fungal infection. The most common antifungal used for treatment of Scedosporium/Lomentospora was posaconazole (n = 16; 53%). Median duration of therapy was 364 days (IQR 164-616). Treatment was associated with improved lung function over 6 months (median FEV1 increased from 1.3L[IQR 0.9-1.8L] to 1.8L[IQR 1.1-2.3] P = .05). Six patients cultured Scedosporium/Lomentospora prior to transplantation, and no survival disadvantage was seen as compared to our whole LTx cohort (P = .8).
CONCLUSION
Our single center 24-year experience suggests that the incidence of Scedosporium/Lomentospora is increasing. Scedosporium/Lomentospora is typically isolated several years after LTx, and requires prolonged anti-fungal treatment that is usually associated with improved in lung function. Culture of Scedosporium/Lomentospora prior to LTx did not pose a survival disadvantage. Further surveillance is required to fully characterize implications of these organisms for LTx recipients.
Topics: Antifungal Agents; Humans; Lung Transplantation; Mycoses; Retrospective Studies; Scedosporium
PubMed: 33315292
DOI: 10.1111/tid.13546 -
Microbiology Spectrum Feb 2023spp. and are an emerging group of fungi refractory to current antifungal treatments. These species largely affect immunocompromised individuals but can also be lung...
spp. and are an emerging group of fungi refractory to current antifungal treatments. These species largely affect immunocompromised individuals but can also be lung colonizers in cystic fibrosis patients. Although Scedosporium apiospermum is thought to be the predominant species, the group has been expanded to a species complex. The distribution of species within the S. apiospermum species complex and other closely related species in the United States is largely unknown. Here, we used β-tubulin and ITS sequences to identify 37 isolates to the species level. These isolates as well as 13 isolates were tested against a panel of nine antifungal drugs, including the first in novel class orotimide, olorofim. and infections are notoriously hard to treat as these organisms can be resistant to numerous antifungals. The manuscript contributes to our knowledge of the activity of the new antifungal agent olorofim and comparator agents against and against isolates that have been molecularly identified to the species level. The efficacy of olorofim against all species of and was confirmed.
Topics: Humans; Antifungal Agents; Scedosporium; Piperazines; Pyrimidines; Ascomycota; Microbial Sensitivity Tests
PubMed: 36629417
DOI: 10.1128/spectrum.02789-22 -
Microbiology Spectrum Jun 2023Infections with spp. and Lomentospora prolificans have become a serious threat in clinical settings. The high mortality rates associated with these infections can be...
Infections with spp. and Lomentospora prolificans have become a serious threat in clinical settings. The high mortality rates associated with these infections can be correlated with their multidrug resistance. The development of alternative treatment strategies has become crucial. Here, we investigate the and activity of luliconazole (LLCZ) against Scedosporium apiospermum (including its teleomorph Pseudallescheria boydii) and . The LLCZ MICs were determined for a total of 37 isolates (31 isolates, 6 Scedosporium apiospermum/ strains) according to EUCAST. Furthermore, the LLCZ antifungal activity was tested , using an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] growth kinetics assay and biofilm assays (crystal violet and XTT assay). In addition, a Galleria mellonella infection model was used for treatment assays. The MIC of LLCZ was determined to be 0.25 mg/L for all tested pathogens. Growth was inhibited within 6 to 48 h of the start of incubation. LLCZ inhibited biofilm formation in both preadhesion stages and late-stage adhesion. , a single dose of LLCZ increased the survival rate of the larvae by 40% and 20% for and spp., respectively. This is the first study demonstrating LLCZ activity against and and the first study showing the antibiofilm effect of LLCZ in spp. and S. apiospermum are opportunistic, multidrug-resistant pathogens causing invasive infections in immunosuppressed patients and sometimes in healthy persons. is panresistant against the currently available antifungals, and both species are associated with high mortality rates. Thus, the discovery of novel antifungal drugs exhibiting an effect against these resistant fungi is crucial. Our study shows the effect of luliconazole (LLCZ) against and spp. , as well as in an infection model. These data reveal the previously unknown inhibitory effect of LLCZ against and its antibiofilm effect in spp. It represents an extension of the literature regarding azole-resistant fungi and could potentially lead to the development of future treatment strategies against these opportunistic fungal pathogens.
Topics: Animals; Humans; Scedosporium; Antifungal Agents; Imidazoles
PubMed: 37017567
DOI: 10.1128/spectrum.05130-22 -
The Journal of Antimicrobial... Jan 2024Little is known about the short- and long-term healthcare costs of invasive Scedosporium/Lomentospora prolificans infections, particularly in patient groups without...
BACKGROUND
Little is known about the short- and long-term healthcare costs of invasive Scedosporium/Lomentospora prolificans infections, particularly in patient groups without haematological malignancy. This study investigated excess index hospitalization costs and cumulative costs of these infections. The predictors of excess cost and length of stay (LOS) of index hospitalization were determined. These estimates serve as valuable inputs for cost-effectiveness models of novel antifungal agents.
METHODS
A retrospective case-control study was conducted at six Australian hospitals. Cases of proven/probable invasive Scedosporium/L. prolificans infections between 2011 and 2021 (n = 34) were matched with controls (n = 66) by predefined criteria. Cost data were retrieved from activity-based costing systems and analysis was performed from the Australian public hospital perspective. All costs were presented in 2022 Australian dollars (AUD). Median regression analysis was used to adjust excess costs of index hospitalization whereas cumulative costs up to 1.5 years follow-up were estimated using interval-partitioned survival probabilities.
RESULTS
Invasive Scedosporium/L. prolificans infections were independently associated with an adjusted median excess cost of AUD36 422 (P = 0.003) and LOS of 16.27 days (P < 0.001) during index hospitalization. Inpatient stay was the major cost driver (42.7%), followed by pharmacy cost, of which antifungal agents comprised 23.8% of the total cost. Allogeneic haematopoietic stem cell transplant increased the excess cost (P = 0.013) and prolonged LOS (P < 0.001) whereas inpatient death within ≤28 days reduced both cost (P = 0.001) and LOS (P < 0.001). The median cumulative cost increased substantially to AUD203 292 over 1.5 years in cases with Scedosporium/L. prolificans infections.
CONCLUSIONS
The economic burden associated with invasive Scedosporium/L. prolificans infections is substantial.
Topics: Humans; Antifungal Agents; Scedosporium; Case-Control Studies; Retrospective Studies; Australia
PubMed: 37944018
DOI: 10.1093/jac/dkad345