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Antimicrobial Agents and Chemotherapy Oct 2021and Fusarium species are emerging opportunistic pathogens, causing invasive fungal diseases in humans, particularly in immunocompromised patients. Biofilm-related...
and Fusarium species are emerging opportunistic pathogens, causing invasive fungal diseases in humans, particularly in immunocompromised patients. Biofilm-related infections are associated with increased morbidity and mortality. Here, we assessed the ability of Scedosporium apiospermum and Fusarium solani species complex (FSSC) isolates to form biofilms and evaluated the efficacy of deoxycholate amphotericin B (D-AMB), liposomal amphotericin B (L-AMB), and voriconazole (VRC), alone or in combination, against mature biofilms. Biofilm formation was assessed by safranin staining and spectrophotometric measurement of optical density. Planktonic and biofilm damage was assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] reduction assay. Planktonic cell and biofilm MICs were determined as the minimum concentrations that caused ≥50% fungal damage compared to untreated controls. The combined activity of L-AMB (0.5 to 32 mg/liter) and VRC (0.125 to 64 mg/liter) against biofilms was determined by the checkerboard microdilution method and analyzed by the Bliss independence model. Biofilm MICs of D-AMB and L-AMB against S. apiospermum isolates were 1 and 2 mg/liter and against FSSC isolates were 0.5 and 1 mg/liter, respectively. Biofilm MICs of VRC against S. apiospermum and FSSC were 32 mg/liter and >256 mg/liter, respectively. Synergistic effects were observed at 2 to 4 mg/liter of L-AMB combined with 4 to 16 mg/liter of VRC against S. apiospermum biofilms (mean Δ ± standard error, 17% ± 3.7%). Antagonistic interactions were found at 0.5 to 4 mg/liter of L-AMB combined with 0.125 to 16 mg/liter of VRC against FSSC isolates, at -28% ± 2%. D-AMB and L-AMB were more efficacious against S. apiospermum and FSSC biofilms than VRC.
Topics: Amphotericin B; Antifungal Agents; Biofilms; Fusarium; Humans; Microbial Sensitivity Tests; Scedosporium; Voriconazole
PubMed: 34370583
DOI: 10.1128/AAC.00638-21 -
Infectious Diseases and Therapy Mar 2020Mould infections may follow traumatic injuries, with direct fungal inoculum in the site of injury and subsequent angioinvasion, possibly resulting in tissue necrosis and... (Review)
Review
Mould infections may follow traumatic injuries, with direct fungal inoculum in the site of injury and subsequent angioinvasion, possibly resulting in tissue necrosis and systemic dissemination. The pathogenesis of mould infections following trauma injuries presents unique features compared with classical mould infections occurring in neutropenic or diabetic patients, because a large fraction of post-traumatic mould infections is observed in previously healthy individuals. Most of the published clinical experience and research on mould infections following traumatic injuries regards soldiers and infections after natural disasters. However, following trauma and soil contamination (e.g., agricultural or automotive injuries) other immunocompetent individuals may develop mould infections. In these cases, delays in correct diagnosis and treatment may occur if pertinent signs such as necrosis and absent or reduced response to antibacterial therapy are not promptly recognized. Awareness of mould infections in at-risk populations is needed to rapidly start adequate laboratory workflow and early antifungal therapy in rapidly evolving cases to improve treatment success and reduce mortality.
PubMed: 32072492
DOI: 10.1007/s40121-020-00284-8 -
Journal of Fungi (Basel, Switzerland) Oct 2021Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically... (Review)
Review
Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). This narrative review concerns 4099 cases of IFIs in 58,784 COVID-19 patients involved in 168 studies. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is a diagnostic challenge because its non-specific clinical/imaging features and the fact that the proposed clinically diagnostic algorithms do not really apply to COVID-19 patients. Forty-seven observational studies and 41 case reports have described a total of 478 CAPA cases that were mainly diagnosed on the basis of cultured respiratory specimens and/or biomarkers/molecular biology, usually without histopathological confirmation. Candidemia is a widely described secondary infection in critically ill patients undergoing prolonged hospitalisation, and the case reports and observational studies of 401 cases indicate high crude mortality rates of 56.1% and 74.8%, respectively. COVID-19 patients are often characterised by the presence of known risk factors for candidemia such as in-dwelling vascular catheters, mechanical ventilation, and broad-spectrum antibiotics. We also describe 3185 cases of mucormycosis (including 1549 cases of rhino-orbital mucormycosis (48.6%)), for which the main risk factor is a history of poorly controlled diabetes mellitus (>76%). Its diagnosis involves a histopathological examination of tissue biopsies, and its treatment requires anti-fungal therapy combined with aggressive surgical resection/debridement, but crude mortality rates are again high: 50.8% in case reports and 16% in observational studies. The presence of other secondary IFIs usually diagnosed in severely immunocompromised patients show that SARS-CoV-2 is capable of stunning the host immune system: 20 cases of pneumonia, 5 cases of cryptococcosis, 4 cases of histoplasmosis, 1 case of coccidioides infection, 1 case of pulmonary infection due to spp., and 1 case of pulmonary infection due to
PubMed: 34829210
DOI: 10.3390/jof7110921 -
Journal of Fungi (Basel, Switzerland) Aug 2019Central nervous system infections due to spp and other hyaline molds such as and spp are rare but fatal conditions. Invasion of the central nervous system (CNS) tends... (Review)
Review
Central nervous system infections due to spp and other hyaline molds such as and spp are rare but fatal conditions. Invasion of the central nervous system (CNS) tends to occur as a result of hematogenous dissemination among immunocompromised patients, and by local extension or direct inoculation secondary to trauma in immunocompetent hosts. Efforts should be directed to confirm the diagnosis by image-guided stereotactic brain biopsy when feasible. Non-culture methods could be useful to support the diagnosis, but they have not been validated to be performed in cerebral spinal fluid. Treatment of these infections is challenging given the variable susceptibility profile of these pathogens and the penetration of antifungal agents into the brain.
PubMed: 31480311
DOI: 10.3390/jof5030079 -
Radiology Case Reports May 2022Voriconazole is a broad-spectrum triazole antifungal used to treat invasive fungal infections. It is commonly used prophylactically in immunocompromized patient cohorts,...
Voriconazole is a broad-spectrum triazole antifungal used to treat invasive fungal infections. It is commonly used prophylactically in immunocompromized patient cohorts, including transplant recipients. Diffuse periostitis is a very rare complication of chronic voriconazole use. It is associated with diffuse bone pain, elevated serum alkaline phosphatase and fluorine levels. Characteristic imaging findings include periosteal thickening with a dense, nodular, irregular and often bilateral pattern. We describe the case of a 71-year-old female who presented with multifocal bone pain six years following double lung transplantation. Her post transplantation course had been complicated by a life threatening episode of sepsis secondary to Scedosporium apiospermum, a rare invasive fungal infection following which lifelong prophylaxis with oral Voriconazole was commenced. We discuss the characteristic clinical and imaging manifestations of this rare condition.
PubMed: 35309380
DOI: 10.1016/j.radcr.2022.01.078 -
BMC Infectious Diseases Jan 2016Lomentospora prolificans (formally Scedosporium prolificans) is an environmental mould with a global distribution. Endocarditis caused by L. prolificans is a rare but... (Review)
Review
BACKGROUND
Lomentospora prolificans (formally Scedosporium prolificans) is an environmental mould with a global distribution. Endocarditis caused by L. prolificans is a rare but serious emerging disease in immunocompromised patients. Prior to this case there have only been eight cases reported in the literature. Diagnosis can be challenging and there are no evidence-based guidelines for treatment.
CASE PRESENTATION
We report a 75-year-old woman with ovarian carcinoma who presented with fever after chemotherapy. Repeated sterile site cultures remained negative until day 22 of admission, when Lomentospora prolificans was isolated from blood cultures. Following extensive investigations, including Fluoro-D-glucose positron emission tomography (FDG-PET) and transoephageal echocardiography (TOE), the patient was diagnosed with endocarditis complicated by cerebral emboli. The patient was considered unsuitable for surgical intervention and passed away five days after the fungus was isolated.
CONCLUSION
Endocarditis caused by Lomentospora prolificans is a rare but emerging condition, with limited treatment options and a high mortality. Awareness of the increasing incidence of Lomentospora prolificans infection, diagnosed often at an advanced stage, with potential for endocarditis may prompt earlier echocardiography or FDG-PET imaging. Further studies are needed to determine the optimal combination and duration of anti-fungal agents, used in conjunction with aggressive surgical excision where feasible.
Topics: Aged; Antineoplastic Agents; Brain; Carboplatin; Echocardiography; Endocarditis; Female; Humans; Magnetic Resonance Imaging; Ovarian Neoplasms; Positron-Emission Tomography; Radiography; Scedosporium
PubMed: 26822980
DOI: 10.1186/s12879-016-1372-y -
Vaccines Dec 2019The high mortality rates of infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic...
The high mortality rates of infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using , , and , and their sera used to identify the most immunoreactive proteins of total extract and secreted proteins. The results showed that was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between species, but not with . Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by species in both secretome and total extract. In conclusion, this study identifies antigens of that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.
PubMed: 31835471
DOI: 10.3390/vaccines7040212 -
Medical Hypothesis, Discovery &... 2021(SA) is commonly present in temperate climates. It can induce cutaneous and subcutaneous tissue infections as well as disseminated infections in immunocompromised or... (Review)
Review
BACKGROUND
(SA) is commonly present in temperate climates. It can induce cutaneous and subcutaneous tissue infections as well as disseminated infections in immunocompromised or immunocompetent hosts. The eye is rarely involved. Keratomycosis is usually caused by plant-related injuries. Here, we describe a patient with a severe and sight-threatening corneal abscess caused by SA, which was associated with contact lens wear and was successfully treated with a combination of surgical and medical therapies.
CASE PRESENTATION
An otherwise healthy 22-year-old woman, with history of contact lens wearing, was referred to the Ophthalmic Department of Bari University, Bari, Italy for evaluation of a corneal abscess and hypopyon in her left eye. Intensive topical and systemic antibiotic therapy was initiated after obtaining con- junctival swabs. Within 2 days, her ophthalmic condition had worsened, and her best-corrected visual acuity (BCVA) dropped to counting fingers. She underwent penetrating keratoplasty, after which her ophthalmic condition improved. Microbiological culture, obtained from the explanted cornea, revealed SA infection. This was addressed with specific topical and systemic therapy using voriconazole. Two weeks later, the con- dition of her left eye was stable, with mild corneal edema and no sign of acute graft rejection. Her BCVA improved to 20/25, and all medications were discontinued, except for the steroid eye drop. The patient was scheduled for a 1-month follow-up.
CONCLUSIONS
Prompt identification of the etiological agent is mandatory to perform appropriate therapy in cases of keratomycosis. Surgery to remove the infected cornea is helpful in patients with deteriorating condition, in whom the initial medical therapy has failed. Topical and systemic antimycotic therapy, based on microbiological culture, is recommended as an adjunctive therapy for the surgical management of severe corneal mycotic abscesses.
PubMed: 37641616
DOI: 10.51329/mehdiophthal1425 -
Clinical Microbiology and Infection :... Aug 2016The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based... (Review)
Review
The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based identification of Aspergillus remains limited to the section or species-complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care.
Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus; Drug Resistance, Fungal; Genes, Fungal; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Population Surveillance; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 27263029
DOI: 10.1016/j.cmi.2016.05.013 -
Medical Mycology Apr 2018Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows... (Review)
Review
Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows for the entrapment of airborne bacteria and fungal spores and provides a suitable environment for growth of microorganisms, including numerous yeast and filamentous fungal species. As a consequence, respiratory infections are the major cause of morbidity and mortality in this clinical context. Although bacteria remain the most common agents of these infections, fungal respiratory infections have emerged as an important cause of disease. Therefore, the International Society for Human and Animal Mycology (ISHAM) has launched a working group on Fungal respiratory infections in Cystic Fibrosis (Fri-CF) in October 2006, which was subsequently approved by the European Confederation of Medical Mycology (ECMM). Meetings of this working group, comprising both clinicians and mycologists involved in the follow-up of CF patients, as well as basic scientists interested in the fungal species involved, provided the opportunity to initiate collaborative works aimed to improve our knowledge on these infections to assist clinicians in patient management. The current review highlights the outcomes of some of these collaborative works in clinical surveillance, pathogenesis and treatment, giving special emphasis to standardization of culture procedures, improvement of species identification methods including the development of nonculture-based diagnostic methods, microbiome studies and identification of new biological markers, and the description of genotyping studies aiming to differentiate transient carriage and chronic colonization of the airways. The review also reports on the breakthrough in sequencing the genomes of the main Scedosporium species as basis for a better understanding of the pathogenic mechanisms of these fungi, and discusses treatment options of infections caused by multidrug resistant microorganisms, such as Scedosporium and Lomentospora species and members of the Rasamsonia argillacea species complex.
Topics: Antifungal Agents; Cystic Fibrosis; Drug Resistance, Multiple, Fungal; Fungi; Genomics; Humans; Microbiological Techniques; Mycoses; Respiratory Tract Infections; Scedosporium
PubMed: 29538733
DOI: 10.1093/mmy/myx106