Leveraging Fungal and Human Calcineurin-Inhibitor Structures, Biophysical Data, and Dynamics To Design Selective and Nonimmunosuppressive FK506 Analogs

Invasive fungal infections are a leading cause of death in the immunocompromised patient population. The rise in drug resistance to current antifungals highlights the urgent need to develop more efficacious and highly selective agents.

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Comparative Efficacy of Amphotericin B Lipid Complex and Liposomal Amphotericin B for the Treatment of Invasive Fungal Infections in HSCT Recipients and other Immunocompromised Patient Populations with Hematologic Malignancies: A Critical Review

The Open Transplantation Journal ◽

10.2174/1874418401105010023 ◽

2011 ◽

Vol 4 (1) ◽

pp. 23-29 ◽

Cited By ~ 4

Author(s):

Jayesh Mehta

Keyword(s):

Amphotericin B ◽

Critical Review ◽

Liposomal Amphotericin ◽

Fungal Infections ◽

Immunocompromised Patient ◽

Hematologic Malignancies ◽

Invasive Fungal Infections ◽

Comparative Efficacy ◽

Lipid Complex ◽

Amphotericin B Lipid Complex

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Clinically Unsuspected Invasive Fungal Infections in the Setting of Malignancy

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz114.005 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S78-S78

Author(s):

Joshua Hendrix ◽

Gina Prochilo ◽

Virian Serei ◽

Kathriel Brister ◽

Billie Fyfe ◽

...

Keyword(s):

Cause Of Death ◽

Fungal Infections ◽

Antimicrobial Prophylaxis ◽

Clinical Status ◽

Pancreatic Head ◽

Autologous Stem Cell Transplant ◽

Postmortem Examination ◽

Invasive Fungal Infections ◽

Cell Transplant ◽

The 1960S

Abstract Background Hospital autopsy rates are currently less than 5% of all nonmedicolegal deaths, significantly decreased from a peak of 40% to 60% in the 1960s. Studies repeatedly demonstrate that advanced imaging and laboratory tests cannot substitute for postmortem examination. We present three cases of clinically unsuspected invasive fungal infections in the setting of malignancy. Methods and Materials We performed clinical chart reviews, postmortem examination with microbiology cultures and special stains, and literature review of three adult autopsy cases. Results Case 1: 55-year-old man with multiple myeloma 4 days after autologous stem cell transplant who presented with rapidly deteriorating clinical status despite successful treatment for MRSA sepsis; autopsy confirmed cause of death as disseminated Rhizopus infection. Case 2: 65-year-old woman with myelodysplastic syndrome with myeloproliferative overlap and neutropenic fever on antimicrobial prophylaxis, including fluconazole. Cause of fever was presumed to be noninfectious etiology; autopsy confirmed cause of death as disseminated Candida krusei, an opportunistic invasive fungus resistant to fluconazole. Case 3: 28-year-old woman with metastatic high-grade pancreatic neuroendocrine carcinoma. An autopsy was performed for the purposes of tissue retrieval; postmortem examination demonstrated a primary pancreatic head mass with oligometastasis to the liver and disseminated Aspergillus infection. Discussion Studies show discordance between the clinical cause of death suggested by the primary care team and the autopsy findings in up to 19% of cases. Additionally, autopsy confirmed the clinical diagnosis only 29% of the time and found that nearly 5% of antemortem diagnoses were completely refuted. Fungal infections are a frequent cause of missed diagnoses. A multi-institutional study examining 192,095 autopsies reported a 9% prevalence of fungal infections contributing to death, half of which were missed clinically. The most common risk factor was leukemia and the most common pathogen was Aspergillus species.

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1735. Epidemiology of Invasive Fungal Infections During Induction Chemotherapy in Adults With Newly Diagnosed Acute Myeloid Leukemia Without Antifungal Prophylaxis: A Retrospective Cohort Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1598 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S635-S636

Author(s):

Eugenia Miranti ◽

Kyle Enriquez ◽

Bruno Medeiros ◽

Aruna Subramanian ◽

Dora Ho ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Induction Chemotherapy ◽

Patient Population ◽

Myeloid Leukemia ◽

Fungal Infections ◽

Antifungal Prophylaxis ◽

Current Data ◽

Invasive Fungal Infections ◽

Pseudallescheria Boydii ◽

Acute Myeloid

Abstract Background While invasive fungal infections (IFIs) are common in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy, little current data exist on the epidemiology of IFIs in this patient population given widespread use of antifungal prophylaxis. Because our institution does not administer antifungal prophylaxis, we are in a unique position to study the natural history of IFIs in these patients. Methods We evaluated the incidence of IFIs using established definitions in adults with AML undergoing induction chemotherapy at Stanford Health Care from 2012 to 2017. We also analyzed incidence of antifungal treatment, impact of IFI diagnosis on survival, and risk factors for IFI development. Patients were followed for up to 12 weeks after beginning induction chemotherapy. Results Of 488 patients analyzed, 243 were eligible for inclusion. The median age was 57 (interquartile range 45–65). Men composed 134 (55%) of the patients and 157 (65%) where white. Fifty-four (22%) had antecedent myelodysplastic syndrome; most received a “7 + 3” regimen involving cytarabine and an anthracycline. Thirty-one (13%) developed a proven or probable IFI; 104 (43%) developed a proven, probable, or possible IFI. Most IFIs were due to lower respiratory tract disease. Eighteen identified organisms were Candida, including six C. albicans. Eight organisms were mold, including four Aspergillus isolates (all but one A. fumigatus) and one isolate each of Fusarium solani, Rhizomucor, Rhizopus, and Scedosporium apiospermum/Pseudallescheria boydii. One hundred ninety patients (78%) received antifungals during their initial admission and 99 (46%) of patients surviving their initial admission were discharged on antifungals. Only 66.7% of patients with a proven or probable IFI survived through 12 weeks, compared with 92.2% of those without (P = 0.007). Baseline absolute neutrophil count ≤500 cells/μL and longer duration of neutropenia were significantly associated with development of proven or probable IFIs. Conclusion Among patients receiving induction chemotherapy for AML, IFIs due to Candida and mold remain frequent absent antifungal prophylaxis and are associated with worse survival. Our findings support the use of antifungal prophylaxis in this patient population. Disclosures All authors: No reported disclosures.

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