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Indian Journal of Medical Microbiology Jun 2024Patients with hematologic malignancies (HM) are at high risk of invasive lung fungal infections (ILFI). To describe the main characteristics, treatment, and outcomes for...
PURPOSE
Patients with hematologic malignancies (HM) are at high risk of invasive lung fungal infections (ILFI). To describe the main characteristics, treatment, and outcomes for five years in adult patients with HM and fungal pneumonia.
METHODS
We conducted a retrospective study at Instituto Nacional de Cancerología (INCan), a referral tertiary care oncology hospital with 135 beds in Mexico City, Mexico. We included all cases of fungal pneumonia in patients with HM from January 1, 2017, to December 31, 2022. Cases were classified as proven, probable, and possible according to EORTC/MSG criteria 2021.
RESULTS
Two hundred ten patients were included; the mean age was 40 years. The most frequent HM was acute lymphoblastic leukemia (n=74) and acute myeloid leukemia (n=68). One hundred forty patients (66.7%) had severe neutropenia for a median of 16 days. All patients had a CT thorax scan; in 132 (62.9%), multiple nodules were documented. Serum galactomannan (GM) was positive in 21/192 (10.9%) and bronchoalveolar lavage in 9/36 (25%). Fifty-three patients (25.2%) died in the first month. In the multivariate analysis for mortality in the first 30 days, hypoalbuminemia, shock, possible ILFI, and inappropriate antifungal treatment were statistically associated.
CONCLUSIONS
In high-risk HM patients, CT thorax scan and GM help diagnose ILFI. An appropriate antifungal improves mortality.
PubMed: 38925277
DOI: 10.1016/j.ijmmb.2024.100654 -
European Journal of Clinical... Jun 2024To identify pathogenic microorganisms and microbiological risk factors causing high morbidity and mortality in immunocompromised patients requiring invasive mechanical...
PURPOSE
To identify pathogenic microorganisms and microbiological risk factors causing high morbidity and mortality in immunocompromised patients requiring invasive mechanical ventilation due to pneumonia.
METHODS
A retrospective single-center study was performed at the intensive care unit (ICU) of the Department of Internal Medicine at Heidelberg University Hospital (Germany) including 246 consecutive patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia from 08/2004 to 07/2016. Microbiological and radiological data were collected and statistically analyzed for risk factors for ICU and 1-year mortality.
RESULTS
ICU and 1-year mortality were 63.0% (155/246) and 81.0% (196/242), respectively. Pneumonia causing pathogens were identified in 143 (58.1%) patients, multimicrobial infections were present in 51 (20.7%) patients. Fungal, bacterial and viral pathogens were detected in 89 (36.2%), 55 (22.4%) and 41 (16.7%) patients, respectively. Human herpesviruses were concomitantly reactivated in 85 (34.6%) patients. As significant microbiological risk factors for ICU mortality probable invasive Aspergillus disease with positive serum-Galactomannan (odds ratio 3.1 (1.2-8.0), p = 0.021,) and pulmonary Cytomegalovirus reactivation at intubation (odds ratio 5.3 (1.1-26.8), p = 0.043,) were identified. 1-year mortality was not significantly associated with type of infection. Of interest, 19 patients had infections with various respiratory viruses and Aspergillus spp. superinfections and experienced high ICU and 1-year mortality of 78.9% (15/19) and 89.5% (17/19), respectively.
CONCLUSIONS
Patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia showed high ICU and 1-year mortality. Pulmonary Aspergillosis and pulmonary reactivation of Cytomegalovirus at intubation were significantly associated with negative outcome.
PubMed: 38922376
DOI: 10.1007/s10096-024-04883-y -
Annali Italiani Di Chirurgia 2024Aspergillosis is the most common invasive fungal infection among lung transplant recipients (LTRs). Although its incidence is lower than that of bacterial or viral...
AIM
Aspergillosis is the most common invasive fungal infection among lung transplant recipients (LTRs). Although its incidence is lower than that of bacterial or viral infections, it poses a similar or even higher mortality rate due to challenges in early diagnosis, limited treatment options, and various complications. Therefore, we aimed to evaluate the pulmonary aspergillosis cases in our tertiary lung transplant center.
METHODS
A retrospective analysis of 146 LTRs was performed. The demographic data, microbiological and histopathological test results, and radiological findings used for Aspergillus identification were recorded.
RESULTS
Aspergillus spp. was detected in 13 of 146 LTRs (9%), mean age 42.5 ± 14.06 years, an average of 18.9 months after lung transplantation. 3 cases (23%) had Aspergillus growth in tissue culture, and 2 (15.4%) showed fungal elements with septal hyaline fibrils in tissue pathology. Aspergillus spp Polymerase chain reaction (PCR) was positive in bronchoalveolar lavage of 8 (61.5%) cases. In addition, 4 (30.7%) cases had relevant tomography findings. The most common pathogens were A. Terreus (21%), A. Fumigatus (14%), and A. Flavus (14%). The mortality rate was 15%.
CONCLUSIONS
LTRs are at high risk of Aspergillus spp infections. Early diagnosis with microbiological, histopathological, and radiological tests, in addition to well-established prevention strategies, prophylaxis, and treatment will provide a better survival rate for patients.
Topics: Humans; Retrospective Studies; Lung Transplantation; Adult; Invasive Pulmonary Aspergillosis; Tertiary Care Centers; Male; Female; Middle Aged; Postoperative Complications
PubMed: 38918958
DOI: 10.62713/aic.3505 -
Microbiology Spectrum Jun 2024The Platelia Aspergillus Antigen immunoassay is the "gold standard" for Aspergillus galactomannan (GLM) measurement in sera and bronchoalveolar lavage (BAL) for the...
Comparative performance of the Platelia Antigen and Galactomannan antigen Virclia Monotest immunoassays in serum and lower respiratory tract specimens: a "real-life" experience.
The Platelia Aspergillus Antigen immunoassay is the "gold standard" for Aspergillus galactomannan (GLM) measurement in sera and bronchoalveolar lavage (BAL) for the diagnosis of invasive pulmonary aspergillosis (IPA). We evaluated the performance of the Aspergillus GLM antigen Virclia Monotest compared to the Platelia assay. A total of 535 specimens [320 sera, 86 bronchial aspirates (BAs), 70 BAL, and 59 tracheal aspirates (TAs)] from 177 adult patients (72 hematological, 32 Intensive Care Unit, and 73 hospitalized in other wards) were processed for GLM testing upon clinical request. One patient had proven IPA, and 11 had probable disease. After excluding indeterminate Virclia results ( = 38), 396 specimens yielded concordant results (56 positive and 340 negative) and 101 discordant results (Virclia positive/Platelia negative, = 95). The overall agreement between immunoassays was higher for sera ( 0.56) than for BAL ( ≤ 0.24) or BAS and TA ( ≤ 0.22). When considering all specimen types in combination, the overall sensitivity and specificity of the Virclia assay for the diagnosis of proven/probable IPA were 100% and 65%, respectively, and for the Platelia immunoassay, sensitivity and specificity were 91.7% and 89.4%, respectively. The correlation between index values by both immunoassays was strong for serum/BAL ( = 0.73; < 0.001) and moderate for BAS/TA (Rho = 0.52; = 0.001). The conversion of Virclia index values into the Platelia index could be derived by the formula = (11.97 * )/3.62 + ). Data from GLM-positive serum/BAL clinical specimens fitted the regression model optimally ( = 0.94), whereas that of BAS and TA data did not ( = 0.11). Further studies are needed to determine whether the Virclia assay may be an alternative to the Platelia assay for GLM measurement in sera and lower respiratory tract specimens.IMPORTANCEGalactomannan detection in serum or bronchoalveolar fluid specimens is pivotal for the diagnosis of invasive pulmonary aspergillosis (IPA). The Platelia Aspergillus Antigen immunoassay has become the "gold standard" for Aspergillus GLM measurement. Here, we provide data suggesting that the Virclia Monotest assay, which displays several operational advantages compared with the Platelia assay, may become an alternative to the Platelia assay, although further studies are needed to validate this assumption. We also provide a formula allowing the conversion of Virclia index values into Platelia values. The study may contribute toward positioning the Virclia assay within the diagnostic algorithm of IPA.
PubMed: 38916338
DOI: 10.1128/spectrum.03910-23 -
Drugs in Context 2024Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to species. , and... (Review)
Review
BACKGROUND
Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to species. , and are also emerging because of the empirical use of antifungal drugs. This updated review discusses the epidemiology of IFIs as well as antifungal drugs, dosing and potential adverse effects in critically ill children.
METHODS
A PubMed search was conducted with Clinical Queries using the key terms "antifungal", "children", "critical care" AND "paediatric intensive care unit" OR "PICU". The search strategy included clinical trials, randomized controlled trials, meta-analyses, observational studies and reviews and was limited to the English literature in paediatrics.
RESULTS
and spp. are the most prevalent fungi in paediatric IFIs, causing invasive candidiasis infections (ICIs) and invasive aspergillosis infections (IAIs), respectively. These IFIs are associated with high morbidity, mortality and healthcare costs. is the principal spp. associated with paediatric ICIs. The risks and epidemiology for IFIs vary if considering previously healthy children treated in the paediatric intensive care unit or children with leukaemia, malignancy or a severe haematological disease. The mortality rate for IAIs in children is 2.5-3.5-fold higher than for ICIs. Four major classes of antifungals for critically ill children are azoles, polyenes, antifungal antimetabolites and echinocandins.
CONCLUSIONS
Antifungal agents are highly efficacious. For successful treatment outcomes, it is crucial to determine the optimal dosage, monitor pharmacokinetics parameters and adverse effects, and individualized therapeutic monitoring. Despite potent antifungal medications, ICIs and IAIs continue to be serious infections with high mortality rates. Pre-emptive therapy has been used for IAIs. Most guidelines recommend voriconazole as initial therapy of invasive aspergillosis in most patients, with consideration of combination therapy with voriconazole plus an echinocandin in selected patients with severe disease. The challenge is to identify critically ill patients at high risks of ICIs for targeted prophylaxis. Intravenous/per os fluconazole is first-line pre-emptive treatment for spp. whereas intravenous micafungin or intravenous liposomal amphotericin B is alternative pre-emptive treatment.This article is part of the Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.
PubMed: 38915918
DOI: 10.7573/dic.2023-9-2 -
Journal of the Belgian Society of... 2024The air crescent (AC) is a common radiological sign. Even if its commonest aetiology remains pulmonary aspergillosis, various other causes have been described. In this...
The air crescent (AC) is a common radiological sign. Even if its commonest aetiology remains pulmonary aspergillosis, various other causes have been described. In this study, we report four rare causes of ACs seen on chest radiographs that haven't been described in the literature. The differential diagnosis of an air crescent sign on chest radiographs includes oesophageal bezoar, interstitial lung emphysema, central bronchial stenosis and perforated emphysematous cholecystitis.
PubMed: 38911284
DOI: 10.5334/jbsr.3583 -
Scientific Reports Jun 2024Frequent and variant infections are caused by the virtue of opportunistic fungi pathogens. Candidiasis, aspergillosis, and mucormycosis are pathogenic microorganisms...
Frequent and variant infections are caused by the virtue of opportunistic fungi pathogens. Candidiasis, aspergillosis, and mucormycosis are pathogenic microorganisms that give rise to vast fungal diseases that alternate between moderate to fatal in severity. The use of fluconazole as an antifungal drug was limited due to the acquired resistance in some types of Candida and other fungal species. This study aims to consolidate fluconazole's biological effectiveness against several pathogenic fungi. Six active monoterpenes (MTs) of carvacrol, linalool, geraniol, α-terpinene, citronellal, and nerolidol were selected and encapsulated in nanostructure lipid carrier (NLC) with (NLC-Flu-MTs) and/without (NLC-MTs) fluconazole in one nanoformulation to determine if they will act synergistically or not? The synthesized nanoformulation NLC-Flu-MTs and NLC-MTs exhibited very good particle size of 144.5 nm and 138.6 nm for size and zeta potential values of (- 23.5 mV) and (- 20.3 mV), respectively. Transmission electron microscope investigation confirmed that the synthesized NLCs have regular and spherical shape. The abundance and concentration of the six released monoterpenes were determined, as a novel approach, using GC-MS with very good results and validity. In-vitro antifungal screening was done before and after nano co-delivery against seven pathogenic, and aggressive fungi of Candida tropicalis, Candida krusei, Candida glabrata, Geotrichum Candidum, Candidaalbicans, Aspergillus Niger, and mucor circinelloides. Inhibition Zone diameter (IZD) and the minimum inhibitory concentration (MIC) were measured. Nanoformulations NLC-Flu-MTs and NLC-MTs manifested potential and unique biological susceptibility against all the tested microorganisms with reduced (MIC) values, especially against Candida Tropicalis (MIC = 0.97 µg/ml) which represents 16-fold of the value shown by NLC-MTs (MIC = 15.6 µg/ml) and 64-fold of fluconazole free before nanoformulation (MIC = 62.5 µg/ml). The efficiency of nanomaterials, particularly NLC-Flu-MTs, has become evident in the diminishing value of MIC which affirmed the synergism between fluconazole and the other six monoterpenes.
Topics: Antifungal Agents; Fluconazole; Microbial Sensitivity Tests; Monoterpenes; Nanostructures; Lipids; Drug Synergism; Drug Carriers; Particle Size; Candida
PubMed: 38909063
DOI: 10.1038/s41598-024-63149-x -
Journal of Medicinal Chemistry Jun 2024The pathogenic fungus utilizes a cyclic ferrioxamine E (FOXE) siderophore to acquire iron from the host. Biomimetic FOXE analogues were labeled with gallium-68 for...
The pathogenic fungus utilizes a cyclic ferrioxamine E (FOXE) siderophore to acquire iron from the host. Biomimetic FOXE analogues were labeled with gallium-68 for molecular imaging with PET. [Ga]Ga(III)-FOXE analogues were internalized in cells via Sit1. Uptake of [Ga]Ga(III)-FOX 2-5, the most structurally alike analogue to FOXE, was high by both and bacterial . However, altering the ring size provoked species-specific uptake between these two microbes: ring size shortening by one methylene unit (FOX 2-4) increased uptake by compared to that by , whereas lengthening the ring (FOX 2-6 and 3-5) had the opposite effect. These results were consistent both and , including PET imaging in infection models. Overall, this study provided valuable structural insights into the specificity of siderophore uptake and, for the first time, opened up ways for selective targeting and imaging of microbial pathogens by siderophore derivatization.
PubMed: 38907990
DOI: 10.1021/acs.jmedchem.4c00887 -
Medicina 2024
Topics: Humans; Bronchitis; Tracheitis; Aspergillosis; Male; Aspergillus; Middle Aged; Female
PubMed: 38907982
DOI: No ID Found -
Radiographics : a Review Publication of... Jul 2024Fungal musculoskeletal infections often have subacute or indolent manifestations, making it difficult to distinguish them from other diseases and infections, given that... (Review)
Review
Fungal musculoskeletal infections often have subacute or indolent manifestations, making it difficult to distinguish them from other diseases and infections, given that they are relatively uncommon. Fungal infections occur by hematogenous spread, direct inoculation, or contiguous extension and may be related to different risk factors, including immunosuppression and occupational activity. The infection can manifest in isolation in the musculoskeletal system or as part of a systemic process. The fungi may be endemic to certain regions or may be found throughout the world, and this can help to narrow the diagnosis of the etiologic agent. Infections such as candidiasis, cryptococcosis, aspergillosis, and mucormycosis are often related to immunosuppression. On the other hand, histoplasmosis, paracoccidioidomycosis, coccidioidomycosis, and blastomycosis can occur in healthy patients in geographic areas where these infections are endemic. Furthermore, infections can be classified on the basis of the site of infection in the body. Some subcutaneous infections that can have osteoarticular involvement include mycetoma, sporotrichosis, and phaeohyphomycosis. Different fungi affect specific bones and joints with greater prevalence. Imaging has a critical role in the evaluation of these diseases. Imaging findings include nonspecific features such as osteomyelitis and arthritis, with bone destruction, osseous erosion, mixed lytic and sclerotic lesions, and joint space narrowing. Multifocal osteomyelitis and chronic arthritis with joint effusion and synovial thickening may also occur. Although imaging findings are often nonspecific, some fungal infections may show findings that aid in narrowing the differential diagnosis, especially when they are associated with the patient's clinical condition and history, the site of osteoarticular involvement, and the geographic location. RSNA, 2024.
Topics: Humans; Mycoses; Diagnosis, Differential; Musculoskeletal Diseases
PubMed: 38900682
DOI: 10.1148/rg.230176