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15 pages, 747 KiB  
Article
The Etiology of Bloodstream Infections at an Italian Pediatric Tertiary Care Hospital: A 17-Year-Long Series
by Chiara Russo, Marcello Mariani, Martina Bavastro, Alessio Mesini, Carolina Saffioti, Erica Ricci, Elisabetta Ugolotti, Roberto Bandettini and Elio Castagnola
Pathogens 2024, 13(8), 675; https://doi.org/10.3390/pathogens13080675 - 9 Aug 2024
Viewed by 222
Abstract
Knowledge of epidemiology is essential for guiding correct antibiotic prescription, reducing bacteremia-associated mortality, and implementing targeted infection control programs. However, only a few studies have reported on the epidemiology of bloodstream infections (BSIs) in pediatrics. We performed a retrospective analysis of all BSIs [...] Read more.
Knowledge of epidemiology is essential for guiding correct antibiotic prescription, reducing bacteremia-associated mortality, and implementing targeted infection control programs. However, only a few studies have reported on the epidemiology of bloodstream infections (BSIs) in pediatrics. We performed a retrospective analysis of all BSIs (excluding those caused by common skin contaminants) diagnosed from 2006 to 2022 in patients younger than 18 years who were treated at an Italian pediatric tertiary care hospital. Overall, 2395 BSIs were recorded, including 2207 (92.15%) due to bacteria and 188 (7.85%) due to fungi. The incidence rate (BSIs/10,000 hospital discharges, IR) of bacterial BSIs significantly increased during the study period. In particular, BSIs caused by S. aureus (including MRSA), Enterobacterales (including ESBL and AmpC producers), Enterococcus spp., and P. aeruginosa became more common. The frequency of carbapenem-resistant strains was <1% and stable over time. Conversely, there was a significant reduction in the incidence of BSIs due to S. pneumoniae. The BSIs were stratified by patient age, and S. aureus was the most frequent cause of BSIs in all age groups, while E. coli was the most frequent in the Enterobacterales family. S. agalactiae was the third most frequent cause of neonatal early-onset BSIs. The prevalence of Enterococcus spp. increased in the subgroups from 8 days to 5 years of age, while P. aeruginosa became more prevalent in children over 5 years of age. S. aureus was also the most frequent isolate in both community- and hospital-onset BSIs, followed by E. coli. The prevalence of multidrug-resistant (MDR) pathogens was very low. It was <5% for both Gram-positive (i.e., MRSA and VRE) and Gram-negative (ESBL, AmpC, and carbapenem-resistant) pathogens, and MDR pathogens were almost exclusively detected in hospital-onset BSIs. Fungi accounted for just under 8% of BSIs. C. albicans was the most frequently isolated strain, followed by C. parapsilosis. Notably, the IR of fungemia did not change significantly during the study period, in spite of an increase in the absolute number of events. The continuous monitoring of local epidemiology is essential to identify changes in the IRs of pathogens and antibiotic susceptibility and to guide antibiotic treatments, especially in the phase when antibiograms are not yet available. Full article
(This article belongs to the Section Bacterial Pathogens)
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<p>Incidence rate of bacteremias and fungemias by year of observation. Legend: BSI, bloodstream.</p>
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9 pages, 6180 KiB  
Case Report
Endogenous Fusarium Endophthalmitis after Bone Marrow Transplant: A Case Report and Literature Review
by Cindy S. Zhao, Karen Wai, Eubee B. Koo, Ehsan Rahimy, Prithvi Mruthyunjaya, Vinit B. Mahajan and Charles M. T. DeBoer
Vision 2024, 8(3), 44; https://doi.org/10.3390/vision8030044 - 21 Jul 2024
Viewed by 427
Abstract
Purpose: We aim to present a case of disseminated fusariosis that occurred in the setting of immunosuppression and presented with bilateral endogenous endophthalmitis, along with a literature review of Fusarium endophthalmitis, highlighting management strategies. Observation: A 70-year-old male with acute myeloid leukemia who [...] Read more.
Purpose: We aim to present a case of disseminated fusariosis that occurred in the setting of immunosuppression and presented with bilateral endogenous endophthalmitis, along with a literature review of Fusarium endophthalmitis, highlighting management strategies. Observation: A 70-year-old male with acute myeloid leukemia who had recently undergone a bone marrow transplant noted bilateral floaters and decreased vision. He was found to have bilateral Fusarium endophthalmitis, with subsequent evidence of fungemia and fusariosis in his skin and joints. Despite aggressive local and systemic treatment, he succumbed to the disease. Endophthalmitis was initially stabilized with pars plana vitrectomy and intravitreal amphotericin and voriconazole until the patient transitioned to comfort measures. A review of 31 cases demonstrates that outcomes are poor and that the disease must be treated aggressively, often both systemically and surgically. Conclusion: This case highlights the recalcitrance of Fusarium bacteremia and Fusarium endophthalmitis. Full article
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<p>B-scan ultrasonography of macular lesions in the left eye on initial examination demonstrated vitreous opacities consistent with vitritis, elevated subretinal lesions, and a thickened choroid.</p>
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<p>Magnetic resonance imaging of the brain and orbit at the time of initial diagnosis showed abnormal thickening of the left sclera and periorbital soft tissues but no lesions infiltrating the optic nerve to suggest malignancy.</p>
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<p>(<b>a</b>) View of vitritis and subretinal lesions in the right eye during diagnostic vitrectomy and prior to core vitrectomy. (<b>b</b>) View of subretinal lesions in the right eye during diagnostic vitrectomy and after core vitrectomy.</p>
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<p>(<b>a</b>) Right eye post-operative day 2 after diagnostic vitrectomy of the right eye. (<b>b</b>) The left eye on the same day.</p>
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20 pages, 1206 KiB  
Review
Neonatal Gut Mycobiome: Immunity, Diversity of Fungal Strains, and Individual and Non-Individual Factors
by Alexandra Mpakosi, Rozeta Sokou, Martha Theodoraki and Christiana Kaliouli-Antonopoulou
Life 2024, 14(7), 902; https://doi.org/10.3390/life14070902 - 19 Jul 2024
Viewed by 526
Abstract
The human gastrointestinal ecosystem, or microbiome (comprising the total bacterial genome in an environment), plays a crucial role in influencing host physiology, immune function, metabolism, and the gut–brain axis. While bacteria, fungi, viruses, and archaea are all present in the gastrointestinal ecosystem, research [...] Read more.
The human gastrointestinal ecosystem, or microbiome (comprising the total bacterial genome in an environment), plays a crucial role in influencing host physiology, immune function, metabolism, and the gut–brain axis. While bacteria, fungi, viruses, and archaea are all present in the gastrointestinal ecosystem, research on the human microbiome has predominantly focused on the bacterial component. The colonization of the human intestine by microbes during the first two years of life significantly impacts subsequent composition and diversity, influencing immune system development and long-term health. Early-life exposure to pathogens is crucial for establishing immunological memory and acquired immunity. Factors such as maternal health habits, delivery mode, and breastfeeding duration contribute to gut dysbiosis. Despite fungi’s critical role in health, particularly for vulnerable newborns, research on the gut mycobiome in infants and children remains limited. Understanding early-life factors shaping the gut mycobiome and its interactions with other microbial communities is a significant research challenge. This review explores potential factors influencing the gut mycobiome, microbial kingdom interactions, and their connections to health outcomes from childhood to adulthood. We identify gaps in current knowledge and propose future research directions in this complex field. Full article
(This article belongs to the Collection Feature Papers in Microbiology)
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<p>The immature immune system of premature neonates affects the composition of their gut microbiome. CO<sub>2</sub>: Carbon dioxide, IL-22: Interleukin-22, sIgA: Secretory immunoglobulin A, PRRs: Pattern recognition receptors.</p>
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<p>Factors influencing the neonatal gut mycobiome.</p>
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7 pages, 794 KiB  
Case Report
Daily Fungal Cell-Free DNA Testing to Assess Clinical Status during Candida krusei Fungemia
by Jo-Anne H. Young, Xiaoying Liu, Emma Porter, Hannah Sweet, Wei Wang, Anton F. Evans, Chi Zhang and Karam M. Obeid
J. Fungi 2024, 10(7), 449; https://doi.org/10.3390/jof10070449 - 27 Jun 2024
Viewed by 607
Abstract
We present a case of a man immunocompromised due to myelodysplastic syndrome with Candida krusei fungemia who had a rising cell-free DNA (cfDNA) giant magnetoresistance (GMR) signal when tested daily using plasma blood samples. With the rise in GMR signal paralleling the development [...] Read more.
We present a case of a man immunocompromised due to myelodysplastic syndrome with Candida krusei fungemia who had a rising cell-free DNA (cfDNA) giant magnetoresistance (GMR) signal when tested daily using plasma blood samples. With the rise in GMR signal paralleling the development of skin lesions in this patient, we conclude that cfDNA can be used to indicate uncontrolled infection and thus help monitor response to therapy. This index patient provides evidence that an invasive fungal infection requires both direct antifungal therapy and an intact immune system to control the infection. This biosensing platform has been simplified to potentially serve as a point-of-care test, setting it apart by overcoming the three common barriers of cfDNA testing: complexity, cost, and time. Full article
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<p>Timeline of the patient’s myelodysplastic syndrome, leukemia history, and index fungemia. The timeline arrow in light blue represents the history before admission during which the index fungemia occurred. The timeline arrow in darker blue represents the admission during which the index fungemia occurred. <span class="html-italic">C. krusei: Candida krusei</span>; GMR: giant magnetoresistance; Haplo-HCT: haploidentical allogeneic hematopoietic cell transplant; MDS: myelodysplastic syndrome; VRE: vancomycin-resistant <span class="html-italic">Enterococcus faecium</span>.</p>
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<p>Photographs of skin lesions from this index case patient: panel (<b>A</b>): skin lesions located on the right arm and in the right antecubital area; panel (<b>B</b>): skin lesion located on the right side of the neck.</p>
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9 pages, 2375 KiB  
Case Report
Rhodotorula mucilaginosa Fungemia in an Infected Biloma Patient Following a Traumatic Liver Injury
by Mohammad Nizam Mokhtar, Raha Abdul Rahman, Farah Hanim Abdullah, Izzuddin Azaharuddin, Azarinah Izaham and Chuan Hun Ding
Healthcare 2024, 12(9), 880; https://doi.org/10.3390/healthcare12090880 - 24 Apr 2024
Viewed by 995
Abstract
Rhodotorula mucilaginosa fungemia is rare and highly resistant to antifungal therapy. We herein report a case involving a 31-year-old male admitted after a high-velocity road traffic accident. He sustained a grade IV liver injury with right hepatic vein thrombosis, which necessitated an urgent [...] Read more.
Rhodotorula mucilaginosa fungemia is rare and highly resistant to antifungal therapy. We herein report a case involving a 31-year-old male admitted after a high-velocity road traffic accident. He sustained a grade IV liver injury with right hepatic vein thrombosis, which necessitated an urgent laparotomy. Post-operatively, repeated imaging of the abdomen revealed the presence of a biloma. Percutaneous subdiaphragmatic drainage was carried out but appeared ineffective, prompting a second surgery for an urgent hemi-hepatectomy. The patient was then nursed in the intensive care unit (ICU); however, during his stay in the ICU, he became more sepsis, which was evident by worsening ventilatory support and a rise in septic parameters from the biochemistry parameters. Despite intravenous piperacillin–tazobactam and fluconazole, his septic parameters did not improve and a full septic workup was conducted and was found to be positive for Rhodotorula mucilaginosa from the blood cultures. After discussion with the infectious disease physicians and clinical microbiologists, it was decided to initiate a course of intravenous meropenem and amphotericin B based on minimum inhibitory concentration (MIC) values, considering the patient’s extended ICU stay and catheter use. Eventually, after successfully weaning off mechanical ventilation, the patient was discharged from ICU care. This case underscores the necessity of individualized approaches, combining timely imaging, appropriate drainage techniques, and tailored treatments to optimize outcomes for such intricate post-traumatic complications. Full article
(This article belongs to the Section Critical Care)
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<p>Computed tomography scan of the abdomen non-contrasted phase showing heterogenous areas consisting of hematoma and laceration at segments V, VI, VII, and VIII extending down to the subhepatic region (red arrow). Inferiorly, it extends down to the hepatic flexure, just lateral to the right pararenal space. Another subcapsular collection was seen adjacent to right liver lobe (blue arrow): (<b>a</b>) coronal view, (<b>b</b>) sagittal view, and (<b>c</b>) axial view, with findings as aforementioned.</p>
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<p>Computed tomography scan of the abdomen non-contrasted phase showing heterogenous areas consisting of hematoma and laceration at segments V, VI, VII, and VIII extending down to the subhepatic region (red arrow). Inferiorly, it extends down to the hepatic flexure, just lateral to the right pararenal space. Another subcapsular collection was seen adjacent to right liver lobe (blue arrow): (<b>a</b>) coronal view, (<b>b</b>) sagittal view, and (<b>c</b>) axial view, with findings as aforementioned.</p>
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<p>Salmon-pink colonies of <span class="html-italic">Rhodotorula mucilaginosa</span> on sheep blood agar (<b>left</b>) and on Sabouraud dextrose agar (<b>right</b>). Sheep blood agar was initially used as it is the standard isolation media used for all positive blood cultured in the bacteriology laboratory. Once the organism was found to be yeast, a subculture onto mycological isolation media such as Sabouraud dextrose agar was carried out.</p>
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<p>A Gram stain of the positive blood culture showing budding yeast cells (1000× magnification). The yeast was identified as <span class="html-italic">Rhodotorula mucilaginosa</span> (%ID: 91.9) through biochemical means using the ID 32 C kit (Biomerieux, Marcy-l’Étoile, France). Our isolate’s identity was further confirmed by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI Biotyper, Bruker-Daltonics, Bremen, Germany), which matched its mass spectral pattern with that of <span class="html-italic">Rhodotorula mucilaginosa</span> DSM 70403 DSM.</p>
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12 pages, 577 KiB  
Review
Fungemia by Wickerhamomyces anomalus—A Narrative Review
by Petros Ioannou, Stella Baliou and Diamantis P. Kofteridis
Pathogens 2024, 13(3), 269; https://doi.org/10.3390/pathogens13030269 - 21 Mar 2024
Cited by 2 | Viewed by 1880
Abstract
Wickerhamomyces anomalus has been previously classified as Hansenula anomala, Pichia anomala, and Candida pelliculosa and was recently reclassified in the genus Wickerhamomyces after phylogenetic analysis of its genetic sequence. An increasing number of reports of human infections by W. anomalus have emerged, [...] Read more.
Wickerhamomyces anomalus has been previously classified as Hansenula anomala, Pichia anomala, and Candida pelliculosa and was recently reclassified in the genus Wickerhamomyces after phylogenetic analysis of its genetic sequence. An increasing number of reports of human infections by W. anomalus have emerged, suggesting that this microorganism is an emerging pathogen. The present review aimed to provide data on the epidemiology, antifungal resistance, clinical characteristics, treatment, and outcomes of fungemia by W. anomalus by extracting all the available information from published original reports in the literature. PubMed/Medline, Cochrane Library, and Scopus databases were searched for eligible articles reporting data on patients with this disease. In total, 36 studies involving 170 patients were included. The age of patients with fungemia by W. anomalus ranged from 0 to 89 years; the mean age was 22.8 years, the median age was 2.2 years, with more than 37 patients being less than one month old, and 54% (88 out of 163 patients) were male. Regarding patients’ history, 70.4% had a central venous catheter use (CVC), 28.7% were on total parenteral nutrition (TPN), 97% of neonates were hospitalized in the neonatal ICU (NICU), and 39.4% of the rest of the patients were hospitalized in the intensive care unit (ICU). Previous antimicrobial use was noted in 65.9% of patients. The most common identification method was the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 34.1%, VITEK and VITEK 2 in 20.6%, and ID32 C in 15.3%. W. anomalus had minimal antifungal resistance to fluconazole, echinocandins, and amphotericin B, the most commonly used antifungals for treatment. Fever and sepsis were the most common clinical presentation noted in 95.8% and 86%, respectively. Overall mortality was 20% and was slightly higher in patients older than one year. Due to the rarity of this disease, future multicenter studies should be performed to adequately characterize patients’ characteristics, treatment, and outcomes, which will increase our understanding and allow drawing safer conclusions regarding optimal management. Full article
(This article belongs to the Special Issue Recent Research on Hospital-Acquired Bloodstream Infections)
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<p>Geographical distribution of studies reporting fungemia by <span class="html-italic">W. anomalus</span> worldwide.</p>
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15 pages, 1328 KiB  
Article
First Report of the Emerging Pathogen Kodamaea ohmeri in Honduras
by Bryan Ortiz, Roque López, Carlos Muñoz, Kateryn Aguilar, Fernando Pérez, Isis Laínez-Arteaga, Fernando Chávez, Celeste Galindo, Luis Rivera, Manuel G. Ballesteros-Monrreal, Pablo Méndez-Pfeiffer, Dora Valencia and Gustavo Fontecha
J. Fungi 2024, 10(3), 186; https://doi.org/10.3390/jof10030186 - 28 Feb 2024
Viewed by 1931
Abstract
Kodamaea ohmeri is an environmental yeast considered a rare emerging pathogen. In clinical settings, the correct identification of this yeast is relevant because some isolates are associated with resistance to antifungals. There is a lack of available data regarding the geographical distribution, virulence, [...] Read more.
Kodamaea ohmeri is an environmental yeast considered a rare emerging pathogen. In clinical settings, the correct identification of this yeast is relevant because some isolates are associated with resistance to antifungals. There is a lack of available data regarding the geographical distribution, virulence, and drug resistance profile of K. ohmeri. To contribute to the knowledge of this yeast, this study aimed to describe in depth three isolates of K. ohmeri associated with fungemia in Honduras. The identification of the isolates was carried out by sequencing the ribosomal ITS region. In addition, the susceptibility profile to antifungals was determined, and some properties associated with virulence were evaluated (exoenzyme production, biofilm formation, cell adhesion, and invasion). The isolates showed strong protease, phospholipase, and hemolysin activity, in addition to being biofilm producers. Adherence and invasion capacity were evident in the HeLa and Raw 264.7 cell lines, respectively. This study expands the understanding of the underlying biological traits associated with virulence in K. ohmeri, and it is the first report of the detection and identification of K. ohmeri in Honduras as a cause of human infection. Full article
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<p>Phylogenetic analysis of <span class="html-italic">K. ohmeri</span> based on the internal transcribed spacer (ITS) regions of the 18S rDNA gene of isolates from different geographical regions. The Tamura–Nei genetic distance model and the Neighbor-Joining method, with a bootstrap of 1000 replicates, were used to construct a cladogram. The sequences obtained in this study are shown inside the light blue box.</p>
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<p>Growth of <span class="html-italic">Kodamaea ohmeri</span> in (<b>A</b>) CHROMagar medium (CHROMagar Candida<sup>TM</sup>, Paris, France), (<b>B</b>) CHROMagar<sup>TM</sup> (Becton, Dickinson and Company, Franklin Lakes, NJ, USA), (<b>C</b>) Chromatic<sup>TM</sup> Candida, Liofilchem<sup>®</sup>. (<b>D1</b>) Germ tube production (arrows) of the positive control (<span class="html-italic">C. albicans</span> ATCC 10231). (<b>D2</b>) Germ tube test in <span class="html-italic">K. ohmeri</span> (non-producer). (<b>E1</b>,<b>E2</b>) Photomicrographs with 40× objective of fungal structures obtained from culture on corn flour agar at 30 °C for 48 h of (<b>E1</b>) the positive control (<span class="html-italic">C. albicans</span> ATCC 10231) and (<b>E2</b>) <span class="html-italic">K. ohmeri</span> showing pseudohyphae with ovoid and elongated blastoconidia on the sides.</p>
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<p>Adhesion and invasion assays in HeLa cells. (<b>A</b>) Percentage of HeLa cells that exhibited adherent yeasts; (<b>A1</b>) Micrograph obtained through brightfield microscopy with 40× objective. Giemsa stain showing yeasts and pseudohyphae of strain C-29 adhered to HeLa cells; (<b>B</b>) Number of pseudohyphae per HeLa cell; (<b>B1</b>) Micrograph obtained through brightfield microscopy at 100× objective. Giemsa stain. Pseudohyphae adhered to HeLa cells; (<b>C</b>) Percentage of macrophages per field invaded by strain; (<b>C1</b>) Micrograph obtained through brightfield microscopy at 100× objective. Giemsa stain. Macrophage invaded by blastoconidia of strain C-29.</p>
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12 pages, 1579 KiB  
Article
Evaluation of Blood Cultures from SARS-CoV-2-Positive and Negative Adult Patients
by Bahar Akgün Karapınar, İlvana Çaklovica Küçükkaya, Yasemin Bölükbaşı, Sertaç Küçükkaya, Gonca Erköse Genç, Zayre Erturan, Ali Ağaçfidan and Betigül Öngen
Healthcare 2023, 11(18), 2581; https://doi.org/10.3390/healthcare11182581 - 19 Sep 2023
Viewed by 1267
Abstract
Bacteremia and fungemia are significant causes of morbidity and mortality that frequently occur as co-infections with viral respiratory infections, including SARS-CoV-2. The aim of this study was to evaluate the microorganisms that were isolated from the blood cultures of SARS-CoV-2-positive and negative patients [...] Read more.
Bacteremia and fungemia are significant causes of morbidity and mortality that frequently occur as co-infections with viral respiratory infections, including SARS-CoV-2. The aim of this study was to evaluate the microorganisms that were isolated from the blood cultures of SARS-CoV-2-positive and negative patients and investigate their antimicrobial resistance patterns. A retrospective analysis was performed of 22,944 blood cultures sent to the laboratory between November 2020 and December 2021. Blood culture analyses were performed using the BD Bactec FX automated system. Identification was carried out using conventional methods, namely, VITEK-2 and MALDI-TOF MS. Antibacterial/antifungal susceptibility tests were performed according to EUCAST/CLSI recommendations. SARS-CoV-2 tests were performed with RT-PCR. Culture positivity was detected in 1630 samples from 652 patients. Of these 652 patients, 633 were tested for SARS-CoV-2; 118 (18.6%) were positive and 515 (81.3%) were negative. The bacteria and fungi that were isolated at the highest rate in SARS-CoV-2-positive patients were methicillin-resistant coagulase-negative staphylococci (MR-CoNS) (21.5%), Escherichia coli (12.4%), Klebsiella pneumoniae (12.4%), Candida albicans (1.65%), and Candida glabrata complex (1.65%), while in the negative patients, the highest rates were for E. coli (21.3%), MR-CoNS (13.5%), K. pneumoniae (12.05%), C. albicans (2.1%), Candida parapsilosis (1.1%), and Candida tropicalis (0.9%). No statistically significant difference was determined between COVID-19-positive and negative patients in terms of detection, such as with the Pseudomonas spp., Enterococcus spp., and methicillin-resistant Staphylococcus aureus isolated from the blood cultures (p > 0.05). The most common isolate was MR-CoNS in SARS-CoV-2-positive patients (p = 0.028). Acinetobacter baumannii was more frequent (p = 0.004) and carbapenem-resistant K. pneumoniae was isolated at a higher rate (60% vs. 43%) in SARS-CoV-2-positive patients compared to SARS-CoV-2-negative patients (p > 0.05). These findings highlight the fact that isolation procedures should not be disregarded and the distribution of bacterial/fungal agents of bloodstream infections and their antibiotic resistance should be followed up during a pandemic, such as in the case of COVID-19. Full article
(This article belongs to the Section Coronaviruses (CoV) and COVID-19 Pandemic)
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<p>Antibiotic resistance profiles of the most frequently isolated bacteria. (<b>a</b>) <span class="html-italic">Escherichia coli</span>; (<b>b</b>) <span class="html-italic">Klebsiella pneumoniae</span>; (<b>c</b>) <span class="html-italic">Pseudomonas aeruginosa</span>; (<b>d</b>) <span class="html-italic">Enterococcus</span> spp.; (<b>e</b>) methicillin-resistant <span class="html-italic">Staphylococcus aureus</span>; (<b>f</b>) methicillin-resistant coagulase-negative staphylococcus.</p>
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<p>Antibiotic resistance profiles of the most frequently isolated bacteria. (<b>a</b>) <span class="html-italic">Escherichia coli</span>; (<b>b</b>) <span class="html-italic">Klebsiella pneumoniae</span>; (<b>c</b>) <span class="html-italic">Pseudomonas aeruginosa</span>; (<b>d</b>) <span class="html-italic">Enterococcus</span> spp.; (<b>e</b>) methicillin-resistant <span class="html-italic">Staphylococcus aureus</span>; (<b>f</b>) methicillin-resistant coagulase-negative staphylococcus.</p>
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13 pages, 1934 KiB  
Article
Predictive Performance of Scoring Systems for Mortality Risk in Patients with Cryptococcemia: An Observational Study
by Wei-Kai Liao, Ming-Shun Hsieh, Sung-Yuan Hu, Shih-Che Huang, Che-An Tsai, Yan-Zin Chang and Yi-Chun Tsai
J. Pers. Med. 2023, 13(9), 1358; https://doi.org/10.3390/jpm13091358 - 6 Sep 2023
Viewed by 1030
Abstract
Cryptococcal infection is usually diagnosed in immunocompromised individuals and those with meningeal involvement, accounting for most cryptococcosis. Cryptococcemia indicates a poor prognosis and prolongs the course of treatment. We use the scoring systems to predict the mortality risk of cryptococcal fungemia. This was [...] Read more.
Cryptococcal infection is usually diagnosed in immunocompromised individuals and those with meningeal involvement, accounting for most cryptococcosis. Cryptococcemia indicates a poor prognosis and prolongs the course of treatment. We use the scoring systems to predict the mortality risk of cryptococcal fungemia. This was a single hospital-based retrospective study on patients diagnosed with cryptococcal fungemia confirmed by at least one blood culture collected from the emergency department covering January 2012 and December 2020 from electronic medical records in the Taichung Veterans General Hospital. We enrolled 42 patients, including 28 (66.7%) males and 14 (33.3%) females with a mean age of 63.0 ± 19.7 years. The hospital stay ranged from 1 to 170 days (a mean stay of 44.4 days), and the overall mortality rate was 64.3% (27/42). In univariate analysis, the AUC of ROC for MEWS, RAPS, qSOFA, MEWS plus GCS, REMS, NEWS, and MEDS showed 0.833, 0.842, 0.848, 0.846, 0.846, 0.878, and 0.905. In the multivariate Cox regression analysis, all scoring systems, older age, lactate, MAP, and DBP, indicated significant differences between survivor and non-survivor groups. Our results show that all scoring systems could apply in predicting the outcome of patients with cryptococcal fungemia, and the MEDS displays the best performance. We recommend a further large-scale prospective study for patients with cryptococcal fungemia. Full article
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<p>The trend association between the seasonal temperature and total deceased patient numbers of cryptococcemia. Trend of high temperature and total patients, <span class="html-italic">p</span> = 0.044. Trend of high temperature and deceased patients, <span class="html-italic">p</span> = 0.014; Trend of low temperature and deceased patients, <span class="html-italic">p</span> = 0.030.</p>
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<p>The AUC of ROC for MEDS, NEWS, qSOFA, MEWS plus GCS, REMS, RAPS, and MEWS indicated 0.905, 0.878, 0.848, 0.846, 0.846, 0.842, and 0.833 to predict the mortality risks of patients with cryptococcemia. AUC, area under the curve; GCS, Glasgow coma scale; MEDS, Mortality in Emergency Department Sepsis Score; MEWS, Modified Early Warning Score; NEWS, National Early Warning Score; qSOFA, quick Sequential Organ Failure Assessment; RAPS, Rapid Acute Physiology Score; REMS, Rapid Emergency Medicine Score; ROC, receiver operating characteristic curve.</p>
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<p>The cumulative survival rates of patients with cryptococcemia were calculated to predict the 30-day mortality rate using Kaplan–Meier analyses. The cut-off point of MEDS, NEWS, qSOFA, MEWS plus GCS, REMS, RAPS, and MEWS was 4, 5, 1, 3, 8, 3, and 3, respectively. GCS, Glasgow coma scale; MEDS, Mortality in Emergency Department Sepsis Score; MEWS, Modified Early Warning Score; NEWS, National Early Warning Score; qSOFA, quick Sequential Organ Failure Assessment; RAPS, Rapid Acute Physiology Score; REMS, Rapid Emergency Medicine Score.</p>
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<p>The overall mortality case numbers of MEDS, NEWS, qSOFA, MEWS plus GCS, REMS, RAPS, and MEWS were 25, 22, 13, 20, 14, 15, and 16, with the overall mortality rate of 89.3%, 91.7%, 92.9%, 87.0%, 100%, 100%, and 88.9% if the cut-off point was more than 4, 5, 1, 3, 8, 3, and 3, respectively.GCS, Glasgow coma scale; MEDS, Mortality in Emergency Department Sepsis Score; MEWS, Modified Early Warning Score; NEWS, National Early Warning Score; qSOFA, quick Sequential Organ Failure Assessment; RAPS, Rapid Acute Physiology Score; REMS, Rapid Emergency Medicine Score.</p>
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10 pages, 269 KiB  
Article
Clinical Features of Cryptococcal Meningoencephalitis in HIV-Positive and -Negative Patients in a Resource-Limited Setting
by Rattagan Kajeekul, Pawut Mekawichai and Methee Chayakulkeeree
J. Fungi 2023, 9(9), 869; https://doi.org/10.3390/jof9090869 - 23 Aug 2023
Cited by 1 | Viewed by 1272
Abstract
Cryptococcal meningoencephalitis is a systemic fungal infection in immunocompromised and immunocompetent individuals. This study investigated the clinical characteristics and factors associated with mortality in HIV-associated and non-HIV-associated cryptococcal meningoencephalitis in a resource-limited setting. This was a retrospective cohort study of patients with cryptococcal [...] Read more.
Cryptococcal meningoencephalitis is a systemic fungal infection in immunocompromised and immunocompetent individuals. This study investigated the clinical characteristics and factors associated with mortality in HIV-associated and non-HIV-associated cryptococcal meningoencephalitis in a resource-limited setting. This was a retrospective cohort study of patients with cryptococcal meningoencephalitis between January 2009 and December 2019 at a tertiary teaching hospital in Thailand. Overall, 1019 patients with cryptococcal meningoencephalitis were enrolled, and 923 (90.6%) were HIV-positive. The patients with HIV-associated cryptococcal meningoencephalitis were younger than the HIV-negative patients (37 versus 56 years, p < 0.01). The HIV-negative patients were more likely to have underlying conditions (52.1% versus 7.5%; p < 0.01), had a longer median duration of headaches prior to admission (14 days versus 6 days, p < 0.01), and were more likely to have an altered mental status at presentation (36.5% versus 18.6%, p < 0.01) and pulmonary involvement (15.6% versus 0.8%, p < 0.01). The HIV-positive patients had lower cerebrospinal fluid (CSF) white blood cell counts (4 versus 94 cells/mm3; p < 0.01), lower CSF protein (69 versus 157 mg/dL; p < 0.01), higher CSF glucose (38.8 versus 21 mg/dL; p < 0.01), and more frequent cryptococcemia (44.1% versus 20.5%; p < 0.01). The mortality rate was high but not significantly different between the two groups (30.2% versus 33.2%; p = 0.53). The HIV-positive patients with comorbidities, fever, an altered mental status at presentation, a CSF white blood cell count below 20 cell/mm3, fungemia, and positive CSF India ink were independently associated with 30-day mortality. In comparison, an altered mental status at presentation and fungemia were associated with 30-day mortality in HIV-negative patients. In conclusion, HIV-negative patients with cryptococcal meningoencephalitis had more extensive central nervous system inflammation, although the two groups’ mortality rates were similar. Unfavorable prognostic factors included comorbidities, fever, an altered mental status at presentation, a low CSF white blood cell count, fungemia, and positive CSF India ink. Full article
(This article belongs to the Section Fungal Pathogenesis and Disease Control)
11 pages, 1790 KiB  
Article
Tocilizumab Is Associated with Increased Risk of Fungal Infections among Critically Ill Patients with COVID-19 and Acute Renal Failure: An Observational Cohort Study
by Barrett J. Burger, Sarenthia M. Epps, Victor M. Cardenas, Rajani Jagana, Nikhil K. Meena and William T. Atchley
Life 2023, 13(8), 1752; https://doi.org/10.3390/life13081752 - 16 Aug 2023
Cited by 2 | Viewed by 1267
Abstract
Research Question: Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19? Background: Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody [...] Read more.
Research Question: Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19? Background: Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has found a role as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections. We sought to assess the risk of invasive fungal disease and the therapeutic impact of tocilizumab on the hospital length of stay, duration of mechanical ventilation, and intensive-care-unit length of stay in critically ill patients with severe coronavirus-19 pneumonia. Methods: Records of critically ill patients with coronavirus-2019 admitted from March to September 2020 at our institution were reviewed. The risk for fungal infections, intensive-care-unit length of stay, hospital length of stay, and duration of mechanical ventilation in those that received tocilizumab in addition to standard coronavirus-2019 treatments was assessed. Results: Fifty-six critically ill patients treated with dexamethasone and remdesivir for coronavirus-2019 were included, of which 16 patients also received tocilizumab. The majority of the cohort was African American, Asian, or of other ethnic minorities (53.6%). Invasive fungal infections occurred in 10.7% of all patients, and infection rates were significantly higher in the tocilizumab group than in the control group (31.2% vs. 2.5%, risk difference [RD] = 28.8%, p < 0.01). The increased risk in the tocilizumab group was strongly associated with renal replacement therapy. There was a dose–response relationship between the risk of fungal infection and number of tocilizumab doses received, with 2.5% of infections occurring with zero doses, 20% with a single dose (RD = 17.5%), and 50% with two doses (RD = 47.5%) (trend test p < 0.001). In addition, ICU LOS (23.4 days vs. 9.0 days, p < 0.01), the duration of mechanical ventilation (18.9 vs. 3.5 days, p = 0.01), and hospital length of stay (LOS) (29.1 vs. 15.5, p < 0.01) were increased in patients that received tocilizumab. Conclusions: Repurposed immunomodulator therapies, such as tocilizumab, are now recommended treatments for severe coronavirus-2019 pneumonia, but safety concerns remain. In this early pandemic cohort, the addition of tocilizumab to dexamethasone was associated with an increased risk of fungal infection in those that were critically ill and received renal replacement therapy. Tocilizumab use was also associated with increased ICU and hospital LOSs and duration of mechanical ventilation. Full article
(This article belongs to the Special Issue COVID-19 Prevention and Treatment: 2nd Edition)
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<p>(Top to bottom, L to R) Numerical distribution of number of days hospitalized for patients who did not receive tocilizumab and those who did, number of days in the ICU for patients who did not receive tocilizumab and those who did, and number of days mechanically ventilated for patients who did not receive tocilizumab and those who did.</p>
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<p>Kernel population density distribution of mean hospital days in patients who received tocilizumab (<b>top</b>), those who did not (<b>middle</b>), and box plot (<b>bottom</b>) showing the IQR of those who did (y) and did not (n) receive tocilizumab.</p>
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<p>Kernel population density distribution of mean ICU days in patients who received tocilizumab (<b>top</b>), those who did not (<b>middle</b>), and box plot (<b>bottom</b>) showing the IQR of those who did (y) and did not (n) receive tocilizumab.</p>
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<p>Kernel population density distribution of mean ventilator days in patients who received tocilizumab (<b>top</b>), those who did not (<b>middle</b>), and box plot (<b>bottom</b>) showing the IQR of those who did (y) and did not (n) receive tocilizumab.</p>
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16 pages, 809 KiB  
Review
Rare Yeasts in Latin America: Uncommon Yet Meaningful
by Óscar Gil, Juan Camilo Hernández-Pabón, Bryan Tabares, Carlos Lugo-Sánchez and Carolina Firacative
J. Fungi 2023, 9(7), 747; https://doi.org/10.3390/jof9070747 - 14 Jul 2023
Cited by 3 | Viewed by 1998
Abstract
Systemic infections caused by rare yeasts are increasing given the rise in immunocompromised or seriously ill patients. Even though globally, the clinical significance of these emerging opportunistic yeasts is increasingly being recognized, less is known about the epidemiology of rare yeasts in Latin [...] Read more.
Systemic infections caused by rare yeasts are increasing given the rise in immunocompromised or seriously ill patients. Even though globally, the clinical significance of these emerging opportunistic yeasts is increasingly being recognized, less is known about the epidemiology of rare yeasts in Latin America. This review collects, analyzes, and contributes demographic and clinical data from 495 cases of infection caused by rare yeasts in the region. Among all cases, 32 species of rare yeasts, distributed in 12 genera, have been reported in 8 Latin American countries, with Trichosporon asahii (49.5%), Rhodotorula mucilaginosa (11.1%), and Saccharomyces cerevisiae (7.8%) the most common species found. Patients were mostly male (58.3%), from neonates to 84 years of age. Statistically, surgery and antibiotic use were associated with higher rates of Trichosporon infections, while central venous catheter, leukemia, and cancer were associated with higher rates of Rhodotorula infections. From all cases, fungemia was the predominant diagnosis (50.3%). Patients were mostly treated with amphotericin B (58.7%). Crude mortality was 40.8%, with a higher risk of death from fungemia and T. asahii infections. Culture was the main diagnostic methodology. Antifungal resistance to one or more drugs was reported in various species of rare yeasts. Full article
(This article belongs to the Section Fungal Pathogenesis and Disease Control)
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<p>Number of cases of rare yeast infections, per million inhabitants, reported in eight Latin American countries between 1997 and 2022.</p>
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<p>Distribution of species of rare yeasts reported to cause infection in Latin America.</p>
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12 pages, 1525 KiB  
Article
Preemptive Therapy in Cryptococcosis Adjusted for Outcomes
by Fernando Messina, Gabriela Santiso, Alicia Arechavala, Mercedes Romero, Roxana Depardo and Emmanuel Marin
J. Fungi 2023, 9(6), 631; https://doi.org/10.3390/jof9060631 - 30 May 2023
Cited by 1 | Viewed by 2465
Abstract
Cryptococcosis is one of the most serious opportunistic diseases in patients living with HIV. For this reason, early diagnosis and appropriate treatment are important. Objectives. The aim of the study was to understand the development of patients diagnosed with cryptococcosis by detection of [...] Read more.
Cryptococcosis is one of the most serious opportunistic diseases in patients living with HIV. For this reason, early diagnosis and appropriate treatment are important. Objectives. The aim of the study was to understand the development of patients diagnosed with cryptococcosis by detection of Cryptococcus antigen in serum by lateral flow assay (CrAg LFA) without nervous system involvement and with treatment in accordance with the results. Materials and Methods. A retrospective, longitudinal, analytical study was performed. Seventy patients with cryptococcosis initially diagnosed by serum CrAg LFA without meningeal involvement between January 2019 and April 2022 were analyzed for medical records. The treatment regimen was adapted to the results of blood culture, respiratory material, and pulmonary tomography imaging. Results. Seventy patients were included, 13 had probable pulmonary cryptococcosis, 4 had proven pulmonary cryptococcosis, 3 had fungemia, and 50 had preemptive therapy without microbiological or imaging findings compatible with cryptococcosis. Among the 50 patients with preemptive therapy, none had meningeal involvement or cryptococcosis recurrences to date. Conclusion. Preemptive therapy avoided progression to meningitis in CrAg LFA-positive patients. Preemptive therapy with dose adjustment of fluconazole in patients with the mentioned characteristics was useful despite the use of lower doses than recommended. Full article
(This article belongs to the Special Issue Fungal Neglected Tropical Diseases)
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<p>Flow chart with patients included and final results.</p>
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<p>Methodologies used for diagnosis and treatment.</p>
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<p>(<b>a</b>) Small thin-walled cavity and pulmonary nodules in patient with proven CP. (<b>b</b>) Chest CT scan, coronal image showing interstitial pattern with ground-glass view.</p>
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14 pages, 4726 KiB  
Article
Whole-Genome Sequence Analysis of Candida glabrata Isolates from a Patient with Persistent Fungemia and Determination of the Molecular Mechanisms of Multidrug Resistance
by Ha Jin Lim, Min Ji Choi, Seung A. Byun, Eun Jeong Won, Joo Heon Park, Yong Jun Choi, Hyun-Jung Choi, Hyun-Woo Choi, Seung-Jung Kee, Soo Hyun Kim, Myung Geun Shin, Seung Yeob Lee, Mi-Na Kim and Jong Hee Shin
J. Fungi 2023, 9(5), 515; https://doi.org/10.3390/jof9050515 - 26 Apr 2023
Cited by 6 | Viewed by 2118
Abstract
Whole-genome sequencing (WGS) was used to determine the molecular mechanisms of multidrug resistance for 10 serial Candida glabrata bloodstream isolates obtained from a neutropenic patient during 82 days of amphotericin B (AMB) or echinocandin therapy. For WGS, a library was prepared and sequenced [...] Read more.
Whole-genome sequencing (WGS) was used to determine the molecular mechanisms of multidrug resistance for 10 serial Candida glabrata bloodstream isolates obtained from a neutropenic patient during 82 days of amphotericin B (AMB) or echinocandin therapy. For WGS, a library was prepared and sequenced using a Nextera DNA Flex Kit (Illumina) and the MiseqDx (Illumina) instrument. All isolates harbored the same Msh2p substitution, V239L, associated with multilocus sequence type 7 and a Pdr1p substitution, L825P, that caused azole resistance. Of six isolates with increased AMB MICs (≥2 mg/L), three harboring the Erg6p A158fs mutation had AMB MICs ≥ 8 mg/L, and three harboring the Erg6p R314K, Erg3p G236D, or Erg3p F226fs mutation had AMB MICs of 2–3 mg/L. Four isolates harboring the Erg6p A158fs or R314K mutation had fluconazole MICs of 4–8 mg/L while the remaining six had fluconazole MICs ≥ 256 mg/L. Two isolates with micafungin MICs > 8 mg/L harbored Fks2p (I661_L662insF) and Fks1p (C499fs) mutations, while six isolates with micafungin MICs of 0.25–2 mg/L harbored an Fks2p K1357E substitution. Using WGS, we detected novel mechanisms of AMB and echinocandin resistance; we explored mechanisms that may explain the complex relationship between AMB and azole resistance. Full article
(This article belongs to the Section Fungal Genomics, Genetics and Molecular Biology)
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<p>Results of antifungal susceptibility testing and whole-genome sequencing of 10 bloodstream isolates of <span class="html-italic">C. glabrata</span> isolated serially from a patient. Antifungal MICs were interpreted according to the clinical breakpoints or epidemiologic cut-offs of the Clinical and Laboratory Standards Institute guidelines (M60-ED2 and M59-ED3, respectively), and the categories are highlighted with colors (red: highly resistant; purple: resistant; blue: not resistant but intermediate, susceptible-dose dependent, or showing an increased MIC).</p>
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<p>Possible evolution of the antifungal resistance mechanisms of the <span class="html-italic">C. glabrata</span> isolates with the Pdr1p L825P mutation during the course of echinocandin and amphotericin B therapy, as determined by whole-genome sequencing. Persisting mutations in each subpopulation were colored green, pink, or orange. <sup>†</sup> Breakthrough fungemia was defined as fungemia that developed during treatment with the indicated antifungal agents for &gt;72 h. <sup>‡</sup> Newly appearing mutations are marked in each subpopulation. Abbreviations: MFG, micafungin; AMB, amphotericin B; CAS, caspofungin; sub, subpopulation.</p>
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6 pages, 7645 KiB  
Communication
Three Successfully Treated Cases of Lodderomyces elongisporus Fungemia: Case Reports and a Review of the Literature
by Nobuhiro Asai, Yuichi Shibata, Akiko Nakamura, Hiroyuki Suematsu, Atsuko Yamada, Tomoko Ohno, Daisuke Sakanashi, Yuzuka Kawamoto, Narimi Miyazaki, Isao Koita, Hideo Kato, Mao Hagihara, Hirotoshi Ohta and Hiroshige Mikamo
Microorganisms 2023, 11(4), 1076; https://doi.org/10.3390/microorganisms11041076 - 20 Apr 2023
Cited by 2 | Viewed by 2112
Abstract
Fungemia is a fatal systemic infection that can occur in immunocompromised patients. Despite that, antifungal stewardship is spreading widely, but the mortality rate is extremely high, showing 40–60%. Loderomyces elongiporus is a newly morphologically detected pathogen, first described in 1994, followed by isolation [...] Read more.
Fungemia is a fatal systemic infection that can occur in immunocompromised patients. Despite that, antifungal stewardship is spreading widely, but the mortality rate is extremely high, showing 40–60%. Loderomyces elongiporus is a newly morphologically detected pathogen, first described in 1994, followed by isolation in humans in 2008. It has been misrecognized as Candida parapsilosis. Recently, fever attributable to L. elongisporus fungemia cases has been reported, and the etiology and clinical features are still unknown. Here, we present three successfully treated L. elongisporus fungemia cases by echinocandin. In total, 11 cases were reviewed, including ours. Six of the eleven cases (55%) had external devices. All cases had some immunocompromised conditions or underlying diseases, such as diabetes mellitus, lung cancer, etc. Six patients survived, and the remaining five died. Seven patients who had received echinocandin initially survived. Risk factors for L. elongiporus fungemia overlap with those of candidemia. Even though there is no breakpoint for L. elongiporus, echinocandin can be a helpful treatment regimen for L. elongiporus fungemia. Full article
(This article belongs to the Section Medical Microbiology)
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<p>The plate was incubated at 35 °C for 48 h, (<b>A</b>) Colony characteristics of Lodderomyces elongisporus (a), <span class="html-italic">Candida parapsilosis</span> (b) and <span class="html-italic">C. albicans</span> (c) on CHROMagar Candia (CHROMagar, Paris, France). (<b>B</b>) Gram-stain of <span class="html-italic">L. elongisporus</span> from aerobic blood culture bottle. Gram-positive budding yeast were seen (magnification ×100).</p>
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