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Blood Res 2022; 57(S1):

Published online April 30, 2022

https://doi.org/10.5045/br.2022.2022036

© The Korean Society of Hematology

Advances in prophylaxis and treatment of invasive fungal infections: perspectives on hematologic diseases

Hyojin Ahn1, Raeseok Lee1,2, Sung-Yeon Cho1,2, Dong-Gun Lee1,2

1Division of Infectious Diseases, Department of Internal Medicine, 2Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea

Correspondence to : Dong-Gun Lee, M.D., Ph.D.
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
E-mail: symonlee@catholic.ac.kr

Received: February 6, 2022; Revised: April 21, 2022; Accepted: April 22, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Invasive fungal infections (IFIs) are common causes of mortality and morbidity in patients with hematologic diseases. Delayed initiation of antifungal treatment is related to mortality. Aspergillus sp. is the leading cause of IFI followed by Candida sp. Diagnosis is often challenging owing to variable conditions related to underlying diseases. Clinical suspect and prompt management is important. Imaging, biopsy, and non-culture-based tests must be considered together. New diagnostic procedures have been improved, including antigen-based assays and molecular detection of fungal DNA. Among hematologic diseases, patients with acute myeloid leukemia, myelodysplastic syndrome, recipients of hematopoietic stem cell transplantation are at high risk for IFIs. Antifungal prophylaxis is recommended for these high-risk patients. There are continuous attempts to achieve ideal management of IFIs. Scoring system for quality control has been developed with important recommendations of current guidelines. Higher adherence to guidelines is related to decreased mortality in IFIs.

Keywords Hematologic diseases, Invasive fungal infections, Diagnosis, Treatment, Quality control

Article

Review Article

Blood Res 2022; 57(S1): S101-S111

Published online April 30, 2022 https://doi.org/10.5045/br.2022.2022036

Copyright © The Korean Society of Hematology.

Advances in prophylaxis and treatment of invasive fungal infections: perspectives on hematologic diseases

Hyojin Ahn1, Raeseok Lee1,2, Sung-Yeon Cho1,2, Dong-Gun Lee1,2

1Division of Infectious Diseases, Department of Internal Medicine, 2Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea

Correspondence to:Dong-Gun Lee, M.D., Ph.D.
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
E-mail: symonlee@catholic.ac.kr

Received: February 6, 2022; Revised: April 21, 2022; Accepted: April 22, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Invasive fungal infections (IFIs) are common causes of mortality and morbidity in patients with hematologic diseases. Delayed initiation of antifungal treatment is related to mortality. Aspergillus sp. is the leading cause of IFI followed by Candida sp. Diagnosis is often challenging owing to variable conditions related to underlying diseases. Clinical suspect and prompt management is important. Imaging, biopsy, and non-culture-based tests must be considered together. New diagnostic procedures have been improved, including antigen-based assays and molecular detection of fungal DNA. Among hematologic diseases, patients with acute myeloid leukemia, myelodysplastic syndrome, recipients of hematopoietic stem cell transplantation are at high risk for IFIs. Antifungal prophylaxis is recommended for these high-risk patients. There are continuous attempts to achieve ideal management of IFIs. Scoring system for quality control has been developed with important recommendations of current guidelines. Higher adherence to guidelines is related to decreased mortality in IFIs.

Keywords: Hematologic diseases, Invasive fungal infections, Diagnosis, Treatment, Quality control

Fig 1.

Figure 1.Diagnosis of fungal pneumonia in patients with hematologic diseases. a)Evidence of neutrophil count (<500 cells/mL) followed the guideline [14].
Abbreviations: ANC, absolute neutrophil count; BAL, broncho- alveolar lavage; BDG, (1→3) beta- D-glucan; CT, computed tomo-graphy; GM, galactomannan; PCR, polymerase chain reaction.
Blood Research 2022; 57: S101-S111https://doi.org/10.5045/br.2022.2022036

Table 1 . Changes of species distribution in the case of candidemia..

PathogensSeoul St. Mary’s Hospital
(adult hematology unit only)
KoreaUnited StatesAsiaEuropea)
Study period2011–20212011–20162017–2021201320212012201920162011
References[16][17][18][19][20][114]
TotalN=153 (%)N=84 (%)N=69 (%)N=3,564 (%)N=829 (%)N=2,329 (%)N=3,354 (%)N=861 (%)N=750 (%)
Candida albicans38 (24.8)27 (32.1)11 (15.9)1,354 (38.0)353 (42.6)877 (37.7)1,307 (39.0)309 (35.9)(55.2)
Non-C. albicans115 (75.1)57 (67.9)58 (84.1)2,210 (62.0)476 (57.4)1,452 (62.3)2,047 (61.0)552 (64.1)(44.8)
Candida tropicalis55 (35.9)30 (35.7)25 (36.2)557 (15.6)156 (18.8)241 (10.3)292 (8.7)264 (30.7)(7.3)
Candida glabrata25 (16.3)8 (9.5)17 (24.6)589 (16.5)159 (19.2)670 (28.8)949 (28.3)116 (13.5)(15.7)
Candida krusei16 (10.5)10 (11.9)6 (8.7)20 (0.6)15 (1.8)32 (1.4)72 (2.1)6 (0.7)(2.5)
Candida parapsilosis9 (5.9)4 (4.8)5 (7.2)844 (23.7)112 (13.5)389 (16.7)496 (14.8)135 (15.7)(13.7)
Candida lusitaniae4 (2.6)2 (2.4)2 (2.9)26 (0.7)9 (1.1)34 (1.5)66 (2.0)1 (0.1)(1.2)
Candida auris1 (0.1)
Others6 (3.9)3 (3.6)3 (4.3)174 (4.9)24 (2.9)86 (3.7)172 (5.1)30 (3.5)(2.6)

a)Without exact number of cases, only percentage..


Table 2 . Antifungal prophylaxis for patients with hematologic diseases in Seoul St. Mary’s Hospital (last revised January 2022)..

Type of patientsPrimaryAlternative
AML Induction/reinduction chemotherapya)Posaconazole (T)Posaconazole (S)
Fluconazole
HMA/Venetoclasa)
- Secondary/refractory AMLPosaconazole (T)Posaconazole (S)
- Relapsed AML (only in 1st and 2nd cycle)Posaconazole (T)Fluconazole
- OtherwiseFluconazole
Other chemotherapy (neutropenia >7 days)a)Fluconazole
Auto-HSCTa),c)MicafunginFluconazole
Itraconazole
Allo-HSCT (pre-engraftment)a),c)MicafunginItraconazole (S)
Allo-HSCT (in the presence of GVHD)b)Posaconazole (T)Posaconazole (S)
Fluconazole

a)Start from absolute neutrophil count ≤1,000 until resolution of neutropenia. b)Until at least 75 days from start or resolution of significant GVHD. c)Voriconazole is only used as secondary prophylaxis in patients with previous proven or probable IPA history..

Abbreviations: AML, acute myeloid leukemia; GVHD, graft versus host disease; HMA, hypomethylating agent; HSCT, hematopoietic stem cell transplantation; S, Syrup; T, Tablet..


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