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Journal of Fungi (Basel, Switzerland) Mar 2024This study assessed the changes in species distribution and antifungal susceptibility patterns during the coronavirus disease 2019 (COVID-19) pandemic compared with a...
Changing Epidemiology of Clinical Isolates of Species during the Coronavirus Disease 2019 Pandemic: Data Analysis from a Korean Tertiary Care Hospital for 6 Years (2017-2022).
This study assessed the changes in species distribution and antifungal susceptibility patterns during the coronavirus disease 2019 (COVID-19) pandemic compared with a pre-pandemic period in Korea. We retrospectively investigated the specimen, species type, and antifungal susceptibility of isolates obtained between 2016 and 2022. Data between two periods were compared: 2016-2019 (pre-pandemic) and 2020-2022 (pandemic). We included 11,396 clinical isolates of species (5137 isolates in the pre-pandemic and 6259 isolates in the pandemic). The most prevalent species was (50.4%), followed by (22.7%), (12.5%), and complex (12.5%). Their ranks were unchanged; however, their relative isolation ratios varied during the pandemic, exhibiting differences ranging from 0.4 to 2.5 across species. The incidence of candidemia increased during the pandemic (average 1.79 episodes per 10,000 patient days) compared with pre-pandemic levels (average 1.45 episodes per 10,000 patient days) in both intensive-care-unit (ICU) and non-ICU patients. Additionally, complex candidemia increased by 1.6-fold during the pandemic. During the pandemic, and candidemia significantly increased by 1.5- and 1.4-fold in ICU patients. In contrast, complex candidemia surged 2.1-fold in non-ICU patients. These species exhibited reduced resistance to fluconazole, voriconazole, caspofungin, and micafungin in the pandemic compared with the pre-pandemic. This study underscores the heightened incidence of -related infections during the COVID-19 pandemic and emphasizes the importance of ongoing surveillance of species epidemiology beyond the pandemic's scope.
PubMed: 38535202
DOI: 10.3390/jof10030193 -
Frontiers in Cellular and Infection... 2024is a genus of budding yeast that is mainly isolated from environmental samples, and 40 species have been detected. The yeast isolated from human clinical samples...
is a genus of budding yeast that is mainly isolated from environmental samples, and 40 species have been detected. The yeast isolated from human clinical samples usually only contain three species: , and . In this study, we isolated from a blood sample of a six-year-old female with a history of B-cell precursor lymphoblastic leukemia in Japan in 2022. Though the strain was morphologically identified as species by routine microbiological examinations, it was subsequently identified as by sequencing the internal transcribed spacer (ITS) of ribosomal DNA (rDNA). The isolate had amino acid substitutions in ERG11 and FKS1 associated with azole and echinocandin resistance, respectively, in species and showed intermediate-resistant to fluconazole and micafungin. The patient was successfully treated with micafungin. Furthermore, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) detected three novel peaks that are specific for , indicating that MALDI-MS analysis is useful for rapid detection of species in routine microbiological examinations.
Topics: Female; Humans; Child; Antifungal Agents; Blood Culture; Micafungin; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Microbial Sensitivity Tests; Candida; Saccharomycetales
PubMed: 38510957
DOI: 10.3389/fcimb.2024.1361432 -
MBio Apr 2024Recent epidemiological studies documented an alarming increase in the prevalence of echinocandin-resistant (ECR) blood isolates. ECR isolates are known to arise from a...
UNLABELLED
Recent epidemiological studies documented an alarming increase in the prevalence of echinocandin-resistant (ECR) blood isolates. ECR isolates are known to arise from a minor subpopulation of a clonal population, termed echinocandin persisters. Although it is believed that isolates with a higher echinocandin persistence (ECP) are more likely to develop ECR, the implication of ECP needs to be better understood. Moreover, replacing laborious and time-consuming traditional approaches to determine ECP levels with rapid, convenient, and reliable tools is imperative to advance our understanding of this emerging concept in clinical practice. Herein, using extensive and systemic infection models, we showed that high ECP isolates are less effectively cleared by micafungin treatment and exclusively give rise to ECR colonies. Additionally, we developed a flow cytometry-based tool that takes advantage of a SYTOX-based assay for the stratification of ECP levels. Once challenged with various collections of echinocandin-susceptible blood isolates, our assay reliably differentiated ECP levels and predicted ECP levels in real time under and conditions when compared to traditional methods relying on colony-forming unit counting. Given the high and low ECP predictive values of 92.3% and 82.3%, respectively, our assay showed a high agreement with traditional approach. Collectively, our study supports the concept of ECP level determination in clinical settings and provides a robust tool scalable for high-throughput settings. Application of this tool facilitates the interrogation of mutant and drug libraries to further our understanding of persister biology and designing anti-persister therapeutics.
IMPORTANCE
is a prevalent fungal pathogen able to replicate inside macrophages and rapidly develop resistance against frontline antifungal echinocandins. Multiple studies have shown that echinocandin resistance is fueled by the survival of a small subpopulation of susceptible cells surviving lethal concentrations of echinocandins. Importantly, bacterial pathogens that exhibit high antibiotic persistence also impose a high burden and generate more antibiotic-resistant colonies. Nonetheless, the implications of echinocandin persistence (ECP) among the clinical isolates of have not been defined. Additionally, ECP level determination relies on a laborious and time-consuming method, which is prone to high variation. By exploiting systemic infection and models, we showed that isolates with a higher ECP are associated with a higher burden and more likely develop echinocandin resistance upon micafungin treatment. Additionally, we developed an assay that reliably determines ECP levels in real time. Therefore, our study identified isolates displaying high ECP levels as important entities and provided a reliable and convenient tool for measuring echinocandin persistence, which is extendable to other fungal and bacterial pathogens.
Topics: Echinocandins; Candida glabrata; Micafungin; Drug Resistance, Fungal; Microbial Sensitivity Tests; Antifungal Agents; Anti-Bacterial Agents
PubMed: 38501869
DOI: 10.1128/mbio.00072-24 -
European Journal of Clinical... May 2024This study investigates how surfactants affect the in-vitro anti-infective efficacy of micafungin, caspofungin, anidulafungin, and amphotericin B in treating pulmonary...
PURPOSE
This study investigates how surfactants affect the in-vitro anti-infective efficacy of micafungin, caspofungin, anidulafungin, and amphotericin B in treating pulmonary mycoses.
METHODS
MIC values for antifungal agents were determined against Candida krusei (now Pichia kudriavzevii) ATCC 6258, Candida albicans ATCC 90028, and 18 clinical isolates using the broth microdilution method in RPMI medium, following EUCAST recommendations. MIC assays included testing with and without Curosurf® surfactant at 1 mg/mL for C. krusei ATCC 6258 and all C. krusei isolates. Subsequent Time-kill studies in Sabouraud broth involved testing both C. albicans ATCC 90028 and C. krusei ATCC 6258 strains at concentrations equal their respective MIC values, with and without surfactant, using all four antifungals. CFU/mL were assessed at multiple time points up to 24 h. TKCs with different surfactant concentrations for C. krusei ATCC 6258 and mini-TKCs at various concentrations relative to the MIC of C. krusei isolates and the reference strain were conducted with micafungin, anidulafungin, and caspofungin.
RESULTS
MIC results showed that 1 µg/mL surfactant reduced killing of micafungin and anidulafungin against C. krusei, while caspofungin was unaffected. Amphotericin B's MIC decreased by half. TKCs demonstrated significant effects of surfactant on micafungin and anidulafungin against C. krusei, with complete abolition of anidulafungin's activity against C. albicans.
CONCLUSION
This in-vitro study highlights the concentration-dependent inhibitory effect of surfactant on antifungal activity against C. krusei and, to some extent, C. albicans, necessitating further clinical validation for invasive lung mycoses treatment.
Topics: Antifungal Agents; Microbial Sensitivity Tests; Humans; Pulmonary Surfactants; Candida albicans; Candida; Micafungin; Candidiasis; Amphotericin B; Echinocandins; Caspofungin
PubMed: 38483681
DOI: 10.1007/s10096-024-04799-7 -
BMC Infectious Diseases Mar 2024Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of... (Review)
Review
Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.
Topics: Female; Humans; Adolescent; Leukemia, Myeloid, Acute; Candidiasis; Hematologic Neoplasms; Neutropenia
PubMed: 38448809
DOI: 10.1186/s12879-024-09172-9 -
Medical Mycology Case Reports Mar 2024is emerging as a highly resistant species of the complex causing invasive and mucocutaneous infections. In this study, three cases of vulvovaginal candidiasis caused...
is emerging as a highly resistant species of the complex causing invasive and mucocutaneous infections. In this study, three cases of vulvovaginal candidiasis caused by are described and identified by Internal Transcribed Spacer 1-2 sequencing. All isolates were susceptible in vitro to anidulafungin, micafungin, caspofungin, 5-flucytosine, posaconazole, voriconazole, itraconazole, amphotericin B, and showed dose-dependent susceptibility to fluconazole. In two patients, three doses of oral fluconazole were effective, while one patient developed clinical fluconazole resistance with a new relapse after 6 months. Increasing the weekly dose of fluconazole showed to be effective in this patient.
PubMed: 38444800
DOI: 10.1016/j.mmcr.2024.100640 -
Medical Mycology Journal 2024Disseminated trichosporonosis is a rare fungal infection whose risk factors are hematological malignancies and neutropenia. Recently, breakthrough Trichosporon... (Review)
Review
Disseminated trichosporonosis is a rare fungal infection whose risk factors are hematological malignancies and neutropenia. Recently, breakthrough Trichosporon infections after administration of micafungin, the first-line systemic antifungal agent in compromised hosts, have been widely recognized. A man in his seventies about 1 month into chemotherapy for acute megakaryoblastic leukemia presented with a worsening fever and dyspnea. The patient was being administered with empirical micafungin therapy for suspected candidiasis. As the symptoms progressed, scattered erythema appeared on the trunk, some with a dark red vesicle at the center. Blood cultures identified Trichosporon asahii, as did the specimen of the skin biopsy. On the basis also of the presence of pneumonia on chest computed tomography, we confirmed the diagnosis of disseminated trichosporonosis and changed the antifungal agent from micafungin to voriconazole. Blood culture turned out to be negative 1 month after administrating voriconazole. However, the patient died of the leukemia. Our review of previous reports on cutaneous manifestations of disseminated trichosporonosis revealed that despite their morphological diversity, erythema with a red papule or vesicle at the center, implying necrosis, was also observed in previous cases. Our case report suggests that dermatologists should be aware of skin manifestations of disseminated trichosporonosis after micafungin administration, especially in cases of hematological malignancies.
Topics: Male; Humans; Micafungin; Antifungal Agents; Voriconazole; Trichosporonosis; Leukemia, Megakaryoblastic, Acute; Trichosporon; Hematologic Neoplasms; Erythema
PubMed: 38417883
DOI: 10.3314/mmj.23-00009 -
Journal of Global Antimicrobial... Jun 2024This study aimed to identify the resistance mechanisms to micafungin and fluconazole in a clinical isolate of Candida glabrata.
OBJECTIVES
This study aimed to identify the resistance mechanisms to micafungin and fluconazole in a clinical isolate of Candida glabrata.
METHODS
The isolate was whole-genome sequenced to identify amino acid changes in key proteins involved in antifungal resistance, and the isolate was further characterised by pathogenicity-related phenotypic assays that supported the sequencing results.
RESULTS
Amino acid substitutions were detected in 8 of 17 protein candidates. Many of these substitutions were novel, including in CHS3, CHS3B, and KRE5, which are involved in the development of micafungin resistance. Regarding fluconazole resistance, overexpression of efflux pumps was observed. Our isolate did not exhibit an increased virulence potential compared with the control strain; however, a significant increase in chitin content and potential to resist the cell surface disruptant sodium dodecyl sulphate was observed.
CONCLUSIONS
This clinical Candida glabrata isolate experienced a change in cell wall architecture, which correlates with the development of micafungin resistance.
Topics: Candida glabrata; Antifungal Agents; Humans; Micafungin; Chitin; Drug Resistance, Fungal; Microbial Sensitivity Tests; Fluconazole; Whole Genome Sequencing; Candidiasis; Fungal Proteins; Amino Acid Substitution; Cell Wall
PubMed: 38408565
DOI: 10.1016/j.jgar.2024.02.012 -
Case Reports in Ophthalmology 2024The aim of this study was to report a case of ROCM related to nasogastric intubation who was survived by liposomal amphotericin B (LAmB) combination therapy in situ...
INTRODUCTION
The aim of this study was to report a case of ROCM related to nasogastric intubation who was survived by liposomal amphotericin B (LAmB) combination therapy in situ without orbital exenteration.
CASE PRESENTATION
A 44-year-old woman presented with a 1-week history of rapidly enlarging swelling on the right nose, cheek, and lower eyelid after underwent gastrointestinal decompression. The lesions were derived from the nasal area where the nasogastric tube had been placed. Based on the biopsy results and clinical manifestations, ROCM was diagnosed. Immediate combination therapy with intravenous LAmB and micafungin and multisection debridement of the right facial region were applied. Postoperative treatment included cleaning, irrigating, and local dressing of the wound area using LAmB. LAmB was also used daily as binocular eye drops against deep infection on the eyeballs. The patient recovered well 4 months later and remained free of disease after 40 months of follow-up.
CONCLUSION
This case adds to our knowledge on the potential risk of nasogastric intubation for mucormycosis infection. Nasogastric tube may be the source of infection associated with ROCM. This report evaluates the beneficial effect of LAmB combination therapy in situ for cleaning, irrigating, local wound dressing, and eye drops on lesion areas. The combination of LAmB as cleaning, irrigating, local dressing solution, and eye drops to control intraocular and intraorbital ROCM infection has not been previously reported to our knowledge. These methods provide multiple choices to substitute for orbital exenteration on the survival of ROCM patients.
PubMed: 38322311
DOI: 10.1159/000536185 -
Antimicrobial Agents and Chemotherapy Mar 2024Invasive primary surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to...
Invasive primary surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to limit their occurrence. We performed a retrospective single-center cohort study among adult single liver transplant recipients at Duke University Hospital in the period between 1 January 2015 and 31 December 2020. The study aimed to determine the rate of IP-SSI according to the peri-transplant antifungal prophylaxis received. Of 470 adult single liver transplant recipients, 53 (11.3%) received micafungin prophylaxis, 100 (21.3%) received fluconazole prophylaxis, and 317 (67.4%) did not receive systemic antifungal prophylaxis in the peri-transplant period. Ten IP-SSIs occurred among 5 of 53 (9.4%) micafungin recipients, 1 of 100 (1.0%) fluconazole recipients, and 4 of 317 (1.3%) recipients who did not receive antifungal prophylaxis. Our study highlights the limitations of antifungal prophylaxis in preventing invasive IP-SSI after liver transplant surgery. We hypothesize that pathogen, host, and pharmacokinetic-related factors contributed to the occurrence of IP-SSI despite antifungal prophylaxis. Our study reinforces the need for a risk-based, multi-pronged approach to fungal prevention, including targeted antifungal administration in patients with risks for invasive candidiasis and close monitoring, especially among patients with surgically complex procedures, with timely control of surgical leaks.
Topics: Adult; Humans; Antifungal Agents; Fluconazole; Liver Transplantation; Micafungin; Retrospective Studies; Cohort Studies; Surgical Wound Infection; Candidiasis, Invasive; Candida; Candidiasis
PubMed: 38299818
DOI: 10.1128/aac.01279-23