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Cureus May 2023Infective endocarditis (IE) carries high morbidity and mortality. Although minimal in incidence, fungal causes (mostly species) carry the highest mortality among all...
Infective endocarditis (IE) carries high morbidity and mortality. Although minimal in incidence, fungal causes (mostly species) carry the highest mortality among all cases of infective endocarditis. We describe a rare case of a 47-year-old male with a past medical history of cerebral vascular accident (CVA), heart failure with reduced ejection fraction status post (SP) automated implantable cardioverter defibrillator (AICD) placement, paroxysmal atrial fibrillation, coronary artery disease (CAD), infective endocarditis with mitral valve replacement and tricuspid valve replacement, and pulmonary hypertension who presented to the emergency department (ED) with complaints of shortness of breath and weakness for four days. The patient was admitted to the cardiac care unit (CCU) due to persistent hypotension despite being on a continuous milrinone drip at home. The patient was initially started on antimicrobial agents for sepsis most likely secondary to pneumonia. Echocardiographic imaging showed a large vegetation on the tricuspid valve; hence, blood cultures were sent and came back positive for sp. Appropriate antifungals (micafungin) were added to the medication regimen, and the patient was transferred to a tertiary hospital for surgical intervention. Patients with bioprosthetic valve replacement require regular follow-ups as this would allow providers to catch symptoms of developing endocarditis and prevent disease progression. These appointments may also decrease other risk factors for the disease, including but not limited to infected lines.
PubMed: 37313062
DOI: 10.7759/cureus.38951 -
The Journal of Antimicrobial... Aug 2023Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed... (Review)
Review
Primary prophylaxis of invasive fungal diseases in patients with haematological malignancies: 2022 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO).
Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/μL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets. We reviewed the impact of antifungal prophylaxis with triazoles on drug-drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice.
Topics: Humans; Antifungal Agents; Cytochrome P-450 CYP3A; Invasive Fungal Infections; Communicable Diseases; Hematologic Neoplasms; Hematology; Medical Oncology; Triazoles
PubMed: 37311136
DOI: 10.1093/jac/dkad143 -
3 Biotech Jul 2023The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered... (Review)
Review
The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered by fungal species of the genera , , and . There have been cases of mucormycosis, aspergillosis, and candidiasis in COVID-19 patients. The treatments given to these opportunistic fungal infections include polyene like amphotericin B, azoles including imidazoles like ketoconazole, miconazole, and triazoles like fluconazole, voriconazole, itraconazole, Echinocandin derivatives like- caspofungin, micafungin, immunomodulatory therapy, granulocyte transfusion, etc. A successful recovery and the reduction of fatalities depend on prompt diagnosis and treatment. To reduce mortality, advanced techniques to identify such uncommon infections at a very early stage are necessary. This review's goal is to provide a summary of the systemic and superficial opportunistic fungal infections that the COVID-19 survivors were dealing with, including information on illness incidence, pathogenicity, and treatment.
PubMed: 37309405
DOI: 10.1007/s13205-023-03648-2 -
Microbial Cell (Graz, Austria) Jun 2023Autophagy promotes or inhibits cell death depending on the environment and cell type. Our previous findings suggested that Atg1 is genetically involved in the regulation...
Autophagy promotes or inhibits cell death depending on the environment and cell type. Our previous findings suggested that Atg1 is genetically involved in the regulation of Pmk1 MAPK in fission yeast. Here, we showed that Δ displays lower levels of Pmk1 MAPK phosphorylation than did the wild-type (WT) cells upon treatment with a 1,3-β-D-glucan synthase inhibitor micafungin or CaCl, both of which activate Pmk1. Moreover, the overproduction of Atg1, but not that of the kinase inactivating Atg1 activates Pmk1 without any extracellular stimuli, suggesting that Atg1 may promote Pmk1 MAPK signaling activation. Notably, the overproduction of Atg1 induces a toxic effect on the growth of WT cells and the deletion of Pmk1 failed to suppress the cell death induced by Atg1, indicating that the Atg1-mediated cell death requires additional mechanism(s) other than Pmk1 activation. Moreover, gene deletion induces tolerance to micafungin and CaCl, whereas deletion induces severe sensitivities to these compounds. The ΔΔ double mutants display intermediate sensitivities to these compounds, showing that deletion partly suppressed growth inhibition induced by Δ. Thus, Atg1 may act to promote cell death upon micafungin and CaCl stimuli regardless of Pmk1 MAPK activity. Since micafungin and CaCl are intracellular calcium inducers, our data reveal a novel role of the autophagy regulator Atg1 to induce cell death upon calcium overload independent of its role in Pmk1 MAPK activation.
PubMed: 37275474
DOI: 10.15698/mic2023.06.798 -
Species Distribution and Antifungal Susceptibilities of Candida Species Isolated From Blood Culture.Cureus Apr 2023Introduction species (spp.) are among the leading agents of bloodstream infections. Candidemias are a major cause of morbidity and mortality. Having an understanding...
Introduction species (spp.) are among the leading agents of bloodstream infections. Candidemias are a major cause of morbidity and mortality. Having an understanding of epidemiology and antifungal susceptibility patterns in each center is crucial in guiding the management of candidemia. In this study, the species distribution and antifungal susceptibility of spp. isolated from blood culture at the University of Health Sciences, Bursa Yuksek Ihtisas Training & Research Hospital were examined and the first data on the epidemiology of candidemia in our center were presented. Methods A total of 236 strains isolated from blood cultures in our hospital over a four-year period were analyzed and their antifungal susceptibilities were studied retrospectively. Strains were identified at the species complex (SC) level by the germ tube test, morphology in cornmeal-tween 80 medium, and the automated VITEK 2 Compact (bioMérieux, Marcy-l'Étoile, France) system. Antifungal susceptibility tests were performed on VITEK 2 Compact (bioMérieux, Marcy-l'Étoile, France) system. The susceptibilities of the strains to fluconazole, voriconazole, micafungin, and amphotericin B were determined according to Clinical and Laboratory Standards Institute (CLSI) guidelines and epidemiologic cut-off values. Results Of the strains, 131 were (55.5%), 40 were SC (16.9%), 21 were (8.9%), 19 were SC (8.1%), eight were (3.4%), seven were (3.0%), six were (2.6%), two were (0.8%) and two were (0.8%). Amphotericin B resistance was not detected in strains. Micafungin susceptibility was 98.3%, and four SC strains (10%) were intermediate (I) to micafungin. Fluconazole susceptibility was 87.2%. Apart from strains which intrinsically resistant to fluconazole, three (7.5%), one SC (5.3%) strain were resistant (R) to fluconazole, and one (12.5%) strain was wild-type (WT). Voriconazole susceptibility of strains was 98.6%. Two SC strains were I to voriconazole, while one strain was R. Conclusion In this study, the first epidemiological data of candidemia agents in our hospital were presented. It was determined that rare and naturally resistant species did not cause any problem in our center yet. SC strains showed decreased susceptibility to fluconazole, whereas strains were highly susceptible to the four antifungals tested. Close monitoring of these data will help guide the treatment of candidemia.
PubMed: 37252597
DOI: 10.7759/cureus.38183 -
Pharmaceutics Apr 2023is a multidrug-resistant pathogen against which echinocandins are the drug of choice. However, information on how the chitin synthase inhibitor nikkomycin Z influences...
is a multidrug-resistant pathogen against which echinocandins are the drug of choice. However, information on how the chitin synthase inhibitor nikkomycin Z influences the killing activities of echinocandins against is currently lacking. We determined the killing activities of anidulafungin and micafungin (0.25, 1, 8, 16 and 32 mg/L each) with and without nikkomycin Z (8 mg/L) against 15 isolates representing four clades (South Asian n = 5; East Asian n = 3; South African n = 3; South American n = 4, two of which were of environmental origin). Two and one isolates from the South Asian clade harbored mutations in the hot-spot 1 (S639Y and S639P) and 2 (R1354H) regions of the gene, respectively. The anidulafungin, micafungin and nikkomycin Z MIC ranges were 0.015-4, 0.03-4 and 2->16 mg/L, respectively. Anidulafungin and micafungin alone exerted weak fungistatic activity against wild-type isolates and the isolate with a mutation in the hot-spot 2 region of but was ineffective against the isolates with a mutation in the hot-spot 1 region. The nikkomycin Z killing curves were always similar to their respective controls. Twenty-two of sixty (36.7%) anidulafungin plus nikkomycin Z and twenty-four of sixty (40%) micafungin plus nikkomycin Z combinations produced at least 100-fold decreases in the CFUs (synergy), with a 41.7% and 20% fungicidal effect, respectively, against wild-type isolates. Antagonism was never observed. Similar results were found with the isolate with a mutation in hot-spot 2 of , but the combinations were ineffective against the two isolates with prominent mutations in hot-spot 1 of . The simultaneous inhibition of β-1,3 glucan and chitin synthases in wild-type isolates produced significantly greater killing rates than either drug alone. Further studies are warranted to verify the clinical efficacy of echinocandin plus nikkomycin Z combinations against echinocandin susceptible isolates.
PubMed: 37242607
DOI: 10.3390/pharmaceutics15051365 -
Journal of Fungi (Basel, Switzerland) Apr 2023Whole-genome sequencing (WGS) was used to determine the molecular mechanisms of multidrug resistance for 10 serial bloodstream isolates obtained from a neutropenic...
Whole-genome sequencing (WGS) was used to determine the molecular mechanisms of multidrug resistance for 10 serial 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.
PubMed: 37233226
DOI: 10.3390/jof9050515 -
Antimicrobial Agents and Chemotherapy Jun 2023We determined the echinocandin susceptibility and genotypes of 13 clinical isolates of Candida auris that were recovered from 4 patients at a tertiary care center in...
We determined the echinocandin susceptibility and genotypes of 13 clinical isolates of Candida auris that were recovered from 4 patients at a tertiary care center in Salvador, Brazil. Three isolates were categorized as echinocandin-resistant, and they harbored a novel mutation that led to an amino acid change W691L located downstream from hot spot 1. When introduced to echinocandin-susceptible C. auris strains by CRISPR/Cas9, Fks1 W691L induced elevated MIC values to all echinocandins (anidulafungin, 16 to 32×; caspofungin, >64×; micafungin, >64×).
Topics: Humans; Antifungal Agents; Candida auris; Fungal Proteins; Echinocandins; Caspofungin; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 37222585
DOI: 10.1128/aac.00423-23 -
European Review For Medical and... May 2023Voriconazole is a new generation of broad-spectrum antifungal agents commonly used in the treatment of invasive aspergillus infections.
BACKGROUND
Voriconazole is a new generation of broad-spectrum antifungal agents commonly used in the treatment of invasive aspergillus infections.
CASE REPORT
We reported a rare case of myopathy induced by voriconazole, which showed severe muscle pain and significantly elevated myocardial enzymes. Enzymes eventually achieved good efficacy by switching voriconazole to micafungin and the use of L-carnitine.
CONCLUSIONS
This reminded us it was necessary to be vigilant for rare adverse reactions of voriconazole in the population with liver dysfunction, the elderly population, and people with multiple underlying diseases in clinical practice. During medication of voriconazole, close attention should be paid to the occurrence of adverse reactions to avoid life-threatening complications.
Topics: Aged; Humans; Voriconazole; Liver Cirrhosis, Alcoholic; Triazoles; Antifungal Agents; Micafungin
PubMed: 37203807
DOI: 10.26355/eurrev_202305_32288 -
Mitochondrion Jul 2023The antifungal activity of the drug micafungin, a cyclic lipopeptide that interacts with membrane proteins, may involve inhibition of fungal mitochondria. In humans,...
The antifungal activity of the drug micafungin, a cyclic lipopeptide that interacts with membrane proteins, may involve inhibition of fungal mitochondria. In humans, mitochondria are spared by the inability of micafungin to cross the cytoplasmic membrane. Using isolated mitochondria, we find that micafungin initiates the uptake of salts, causing rapid swelling and rupture of mitochondria with release of cytochrome c. The inner membrane anion channel (IMAC) is altered by micafungin to transfer both cations and anions. We propose that binding of anionic micafungin to IMAC attracts cations into the ion pore for the rapid transfer of ion pairs.
Topics: Humans; Micafungin; Mitochondria; Mitochondrial Membranes; Anions; Ion Channels
PubMed: 37201620
DOI: 10.1016/j.mito.2023.05.004