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Review

Invasive Trichosporonosis in Neonates and Pediatric Patients with Malignancies or Hematologic Disorders

Infectious Diseases Unit, 3rd Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece
*
Author to whom correspondence should be addressed.
Pathogens 2022, 11(2), 242; https://doi.org/10.3390/pathogens11020242
Submission received: 16 January 2022 / Revised: 6 February 2022 / Accepted: 7 February 2022 / Published: 12 February 2022

Abstract

:
(1) Background: Trichosporon species have emerged as important opportunistic fungal pathogens, with Trichosporon asahii being the leading and most frequent cause of invasive disease. (2) Methods: We performed a global review focused on invasive trichosporonosis in neonates and pediatric patients with malignancies or hematologic disorders. We reviewed case reports and case series of trichosporonosis due to T. asahii published since 1994, the year of the revised taxonomic classification. (3) Results: Twenty-four cases of invasive trichosporonosis were identified in neonates with the presence of central venous catheter and use of broad-spectrum antibiotics recognized as the main predisposing factors. Thirty-two cases were identified in children with malignancies or hematologic disorders, predominantly with severe neutropenia. Trichosporon asahii was isolated from blood in 24/32 (75%) pediatric cases. Cutaneous involvement was frequently observed in invasive trichosporonosis. Micafungin was the most commonly used prophylactic agent (9/22; 41%). Ten patients receiving prophylactic echinocandins were identified with breakthrough infections. A favorable outcome was reported in 12/16 (75%) pediatric patients receiving targeted monotherapy with voriconazole or combined with liposomal amphotericin B. Overall mortality in neonates and children with malignancy was 67% and 60%, respectively. (4) Conclusions: Voriconazole is advocated for the treatment of invasive trichosporonosis given the intrinsic resistance to echinocandins and poor susceptibility to polyenes.

1. Introduction

Trichosporon species are basidiomycetous yeast-like fungi, which are characterized by the formation of arthroconidia that disarticulate from septate hyaline hyphae [1]. The word Trichosporon is derived from Greek words Tricho (hair) and Sporon (spores). Trichosporon species are found in nature, soil, water, mammals, birds, bats and cattle and also colonize the human skin, gastrointestinal tract and mucosal surfaces as part of the human microbiota [2,3]. They are also responsible for superficial infections (white piedra), allergic pneumonitis and rarely invasive infection [4,5,6,7,8,9,10].
Since the first case of invasive Trichosporon infection (ITI) reported by Watson and Kallichurum in 1970, Trichosporon species have emerged as important opportunistic fungal pathogens [11]. Trichosporon asahii, in particular, is considered to be the leading and most frequent cause of invasive disease [12]. Invasive Trichosporon infection may involve many organs, while Trichosporon fungemia (TF), including catheter-related fungemia, represents the main type of this opportunistic infection, which accounts for between 58.8 and 74.7% of infections [13,14]. In the 1980s, Walsh et al. reported ITI as the second most common cause of fungemia in patients with hematological malignancies [15]. As triazole derivatives became widely available, the incidence of ITI decreased in early the 2000s [16] followed by a re-emergence of Trichosporon as an increasingly common pathogen in immunocompromised hosts after the wide use of echinocandins [16,17,18,19]. Most cases of invasive infection are seen in patients with neutropenia and malignancy, especially in adults and children with hematological malignancies and intravascular indwelling catheters. Premature neonates with a low birth weight, patients with Acquired Immune Deficiency Syndrome (AIDS) and critically ill patients exposed to broad-spectrum antibiotics are also at increased risk [20,21,22,23,24,25,26,27]. Data regarding ITIs in children are based on case reports and small case series. Therefore, we performed this global review in order to increase scientific knowledge and evaluate existing therapeutic strategies aiming for the optimal patient outcome.

2. Results

The literature review yielded 24 neonatal cases and 32 ITIs in children with malignancy or hematologic disorder that fulfilled our inclusion criteria. These cases constituted the basis of the present review (Table 1 and Table 2).

2.1. Neonates

Twenty-four cases of ITI due to T. asahii in neonates were identified. The female/male ratio was 1.14/1. Several occasional outbreaks of trichosporonemia from different Neonatal Intensive Care Units (NICUs) were reported [28,29,30,31,32,33,34,35,36,37,38]. Two outbreaks in a single NICU in India contributed to 11/24 (46%) cases [39,40]. In general, the geographic distribution involved three continents, while many cases originated from countries with temperate and subtropical climates. The median birth weight (BW) of neonates was 960 gr and the median gestational age (GA) was 27 weeks. Among 21 cases with data reported, 19 (90%) occurred in premature neonates. The median postnatal age at diagnosis was 11 days. The presence of central venous catheter (CVC) and use of broad-spectrum antibiotics were reported in the vast majority of cases. Fungemia was reported in 22/24 (92%) neonates. Other specimens that grew Trichosporon spp. were urine, tracheal aspirate and peritoneal fluid. Conventional amphotericin B (AMB) or liposomal amphotericin B (LAMB) were the most frequently used monotherapies. Voriconazole (VRC) exhibited the lowest median minimum inhibitory concentration, (ΜΙC) (0.03 μg/mL) value against T. asahii. Overall mortality in neonates was 16/24 (67%).

2.2. Malignant and/or Hematologic Disorders

Thirty-two cases of ITI were identified related to malignant and/or hematologic disorders. The most common underlying disorder was acute lymphoblastic leukemia (ALL) (13/32; 41%) followed by acute myeloid leukemia (AML) (8/32 cases; 25%). The remaining 34% of the reported cases included three cases with aplastic anemia, two cases with mixed ALL and one case with Blackfan–Diamond, myelodysplastic syndrome (MDS), Langerhans cell histiocytosis, Wilms tumor, Ewing sarcoma and yolk sac tumor, respectively [38,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59]. The male/female ratio was 1/1. The median age was 11.5 years (range:1–18 years). Details about neutropenia were available in 23/32 (72%) patients and the majority (22/23; 96%) developed severe neutropenia (Absolute Neutrophil Count (ANC) ≤ 0.5 × 109 neutrophils/L). Trichosporon asahii was isolated from various types of clinical specimens including blood in 24/32 (75%) patients. Cutaneous involvement with papulonodular or pustular lesions was common and was frequently observed in 7/32 (22%) patients. Susceptibilities of T. asahii to various antifungal agents are shown in Table 3. Of the 32 patients with T. asahii disseminated infection, 18 (56%) had an in vitro susceptibility test. Voriconazole exhibited the lowest median Minimal Inhibitory Concentration (MIC) (0.06 μg/mL) value against T. asahii.
Information about antifungal prophylaxis given before ITI was available in 18/32 (56%) patients, and micafungin was the most commonly agent used (9/18; 50%). Ten patients receiving prophylactic echinocandins (55%) were identified with breakthrough infections. Various empirical treatment regimens were used; LAMB was used as monotherapy in 8/20 (40%) patients and in combination with an azole in 2/20 patients (10%). As targeted monotherapy VRC was administered in 11/22 (50%) patients. The combination of an azole with LAMB was reported in 6/22 (27%), especially VRC in combination with LAMB in 5/22 (23%). A favorable outcome was reported in 12/16 (75%) in patients receiving VRC as monotherapy or in combination with LAMB. Overall mortality in pediatric patients with malignancy and ITI was 60%

3. Discussion

According to our review, invasive trichosporonosis is rarely documented in children and is mainly reported in premature neonates and in immunocompromised children with hematological malignancies. T. asahii is the predominant Trichosporon species that causes invasive infection, especially breakthrough infections in patients receiving prophylactic/empirical antifungal treatment [1,60,61]. It is noteworthy that all pediatric cases are reported in the second half of the 2000s, indicating the re-emergence of this opportunistic fungal pathogen. After candidiasis, trichosporonosis is considered the second most frequent yeast infection leading to fungemia in patients with hematological malignancies [62,63,64]. Moreover, a change in the geographical distribution of cases is noticeable in the second decade of 2000s, since more cases have been reported from South America and Asia. An increasing concern of physicians, as well as the wider availability of more sophisticated molecular diagnostic methods, have played a role but the real epidemiological trend remains to be established.
In pediatric cancer patients, the largest group is comprised of leukemia patients. Among them, patients with ALL are at lower risk for invasive fungal infections (IFIs) compared to children with leukemia relapse or AML. Nevertheless, ALL patients are the largest group in absolute numbers reported with IFIs in children [65]. Our literature review revealed a total of 32 children with malignant and/or hematologic diseases. Among children with hematological malignancies, the majority were children with ALL. In contrast, among adults, the majority were AML patients followed by ALL and MDS [62]. Profound and prolonged neutropenia is an established risk factor for IFIs. In accordance with this, when the ANC was reported, the vast majority of children had neutropenia, highlighting the importance of neutrophil recovery in the prevention of ITI. Moreover, the use of broad-spectrum antibiotics and concomitant bacteremia play a significant role in the imbalance of the microbiota, resulting in potential IFI. Prolonged and severe neutropenia, together with the underlying immune status of the host, play a critical role in the outcome of the infection in children with hematologic or malignant disorder and in neonates [66,67]. The presence of a CVC and the disruption of the mucosal barrier might provide a portal of entry for Trichosporon spp. The formation of Trichosporon biofilms on catheter surfaces is important in the pathogenesis of invasive trichosporonosis [68]. Therefore, catheter removal as source control should be suggested whenever feasible.
Diagnosis is challenging since it relies on the isolation of a yeast-like organism from a clinical specimen. Direct examination seldom contributes to a definite diagnosis as it rarely demonstrates arthroconidia and it resembles Candida in histology. However, it has thinner hyphae and pseudohyphae and is slightly stained with Gomori methenamine silver (GMS) stain. Cutaneous involvement with maculopapular or pustular lesions that are sometimes necrotic is suggestive of trichosporonosis, though it may also be present in disseminated candidiasis. Biopsy and culture specimens of cutaneous lesions are helpful in establishing the diagnosis. Galligan et al. reported a child with relapsed ALL and disseminated T. asahii infection that had cutaneous nodules suggestive of fungal infection [42]. Despite the fact that histologic characteristics resembled Neutrophil Eccrine Hydradenitis, staining with periodic acid-Schiff stain and GMS confirmed the diagnosis of trichosporonosis. Moreover, de Almeida et al. has shown that MALDI–TOF spectrometry could be used as a valuable alternative for routine identification [62]. Direct sequencing of the IGS1 region of the ribosomal DNA is considered the reference method for species identification of Trichosporon isolates [69]. The timing and sensitivity of the diagnostic method is an important factor for successful management of ITIs. Invasive trichosporonosis can involve many organs, but Trichosporon fungemia (TF) including catheter-related fungemia, represents the main type of this opportunistic infection, as depicted in this review.
Prompt initiation of proper antifungal therapy is considered critical for obtaining a favorable outcome. Global guidelines for the management of rare yeasts from the European Confederation of Medical Mycology in collaboration with the International Society for Human and Animal Mycology and American Society for Microbiology have recently been published [70]. Various antifungal agents are available in the treatment of invasive trichosporonosis.
For the neutropenic pediatric patients with potential IFI, prophylactic/empirical treatment with echinocandins or a formulation of AMB has been recommended. Review of the literature revealed ten pediatric cases with breakthrough infections in patients receiving prophylactic echinocandins. Echinocandins are ineffective against Trichosporon spp. Moreover, it has been reported that their use may select for resistant fungal organisms, which explains the re-emergence of this opportunistic fungal pathogen [71]. Amphotericin B has shown some positive effectiveness against Trichosporon spp. in vitro, but it functions poorly with breakthrough infections, particularly in patients with profound neutropenia on high doses of AMB [72]. Walsh et al. reported that 77% of Trichosporon isolates were not killed at achievable AMB serum levels and this finding was correlated with refractory, disseminated trichosporonosis in neutropenic patients [73]. Poor response to AMB has also been reported in adult patients [1,13,67,74]. Nevertheless, successful results with AMB have been reported in neonatal cases with disseminated disease [30,37,39]. Variable susceptibility to AMB in vitro and in vivo may be explained by the production of a biofilm layer. The capability of T. asahii to produce biofilms is well documented in vitro [68]. In addition, an increased antifungal resistance to AMB has been reported to be directly proportional to increased biofilm production [75]. Therefore, the expected response to AMB may not be observed in the clinical setting, despite the in vitro sensitivity to AMB. Resistance to AMB and echinocandins is alarming not only for pediatric patients with neutropenia but also for neonates since they are both commonly used as systemic antifungal agents in preterm neonates. Early diagnosis of trichosporonosis remains a challenge since Trichosporon spp. may be less susceptible to empirical or prophylactic antifungal drugs that are frequently used, such as echinocandins and AMB. Trichosporon spp. seem to be sensitive to AMB in vitro, but this response may not be observed in vivo when a biofilm layer is produced by Trichosporon spp.
Although in vitro and in vivo studies have shown that Trichosporon species are resistant to the fungicidal effect of AMB, antifungal triazoles have been found to be fungicidal against Trichosporon species [67,73]. A favorable outcome in patients who received a VCZ regimen or an AMB–triazole combined regimen was reported by Liao et al. who assessed 185 cases of Trichosporon fungemia [76]. Moreover, Almeida et al. reported that azole-based therapy was a protective factor against adverse outcomes in 199 cases of proven infection and in 4 cases of probable infection caused by Trichosporon spp [62]. In accordance with this, a favorable outcome was reported in 12/16 (75%) pediatric patients receiving targeted monotherapy with VRC or combined with LAMB. However, fatal pediatric cases have been reported in children despite treatment with AMB and VRC [53].
Considering the intrinsic resistance to echinocandins and poor susceptibility to polyenes, triazoles have been proposed as the antifungals of choice for invasive trichosporonosis [77]. Azole-including therapy was more frequently used especially after 2004 [14]. Global guidelines published in 2021 moderately recommend VRC as the initial antifungal therapy, whereas fluconazole is also moderately supported, contingent on the MIC. Weak support exists for combination antifungal therapy [70]. The first successful treatment of ITI with voriconazole was reported in 2002 [78], a finding that has been confirmed in adults and children with IT [79]. According to our results, targeted monotherapy with VRC was reported in 11 pediatric patients with malignancy or hematologic disorder, resulting in a favorable outcome in 8/11(73%) patients. Combination therapy with AMB and a triazole has not been proven to be superior to VRC alone in vitro and requires more clinical studies to be confirmed [1,62,80]. Our review suggests that azole-including therapy may be superior to echinocandin- or AMB- based therapy in children, as it is in adults. According to the recently published global guidelines for the management of rare yeast infections, azole-polyene combinations should be reserved for salvage therapy [70]. Nevertheless, lately multi-drug resistant Trichosporon spp. has been reported with the increased use of broad-spectrum triazoles for prophylaxis in high-risk patients [81]. Multiple drug interactions in patients receiving chemotherapy and pharmacokinetic variability may play a role in the subtherapeutic level of triazoles leading to resistance to triazoles.

4. Materials and Methods

Published cases and case series of ITI in neonates and patients aged ≤18 years with malignancy or non-malignant hematologic disorder were reviewed. Only original full-text articles were included in the analysis. We searched PubMed for publications of case series and single case reports of ITI with the following keywords: “Trichosporon”, “trichosporonosis”, “invasive infection”, “neonates”, “child”, “pediatric malignancy”, “leukemia”, “tumor”. Moreover, the reference list of each article was further assessed in order to verify that all published cases were included in this review. This search was conducted between 1994 (the year of the revised taxonomic classification) and December 2020. Since the vast majority of ITI is due to T. asahii and isolates from invasive deep infections previously reported in the literature as T. beigelii and/or Trichosporon cutaneum would belong to T. asahii, we limited the search to T. asahii. Invasive trichosporonosis was defined according to the definitions of invasive fungal disease of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group consensus group (EORTC/MSG) [82]. Neutropenia was defined as an ANC ≤ 0.5 × 109 neutrophils/L at the time of Trichosporon isolation. Invasive fungal disease was defined as proven infection according to the revised definitions by the EORTC/MSG consensus group [28]. Cases of superficial infection and infection with Trichosporon capitatum or Trichosporon pullulans were excluded as they have been reclassified to a different genus. A master Excel database was created containing study characteristics (first author name, year of publication, geographic location) demographic (sex, age, GA, and BW for neonates), underlying condition, microbiology data including antifungal susceptibility testing (AST), prophylactic/empiric or targeted antifungal treatment, and clinical outcome.

5. Conclusions

Trichosporonosis is an emerging concern in preterm neonates treated with broad-spectrum antimicrobials and indwelling catheters, and in children with hematologic malignant disease receiving prophylaxis or treatment with echinocandins given their lack of efficacy against this yeast. Treatment remains challenging due to the rarity and resistance to standard antifungals and the compromised status of the host. Invasive infection caused by T. asahii is a rare but potentially fatal complication of the immunosuppression associated with cancer treatment and immaturity of the immune system of younger children and should be considered in the differential diagnosis, especially in patients with neutropenia and recalcitrant fever. Voriconazole is considered as the first-choice therapy followed by fluconazole as an alternative. Combined therapy with an azole and LAMB is advocated as salvage therapy. Removal of the CVC and recovery of neutropenia are also considered as key factors for improved outcome. Prompt and aggressive treatment of ITI is important since T. asahii is less susceptible to the recommended empirical or prophylactic antifungal regimens.

Author Contributions

Conceptualization, E.R.; methodology, M.K., E.R.; validation, formal analysis, M.K., E.R.; investigation, M.K., E.R.; resources, M.K., E.R.; data curation, M.K.; writing—original draft preparation, M.K., E.R.; writing—review and editing, M.K., E.R.; supervision, E.R. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

None.

Conflicts of Interest

The authors declare no conflict of interest.

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Table 1. Characteristics of neonatal invasive infections due to Trichosporon spp.
Table 1. Characteristics of neonatal invasive infections due to Trichosporon spp.
Author (yr)Postnatal DaySpeciesSexSite of IsolationWeight (gr)Gestation Age (wks)Medical HistoryTreatmentOutcomeCountry
Noni et al. (2020)n/aasahiiFCathetern/an/aPacemaker insertion, hypotonian/an/aGreece
Basu et al. (2015)9asahiiMBlood92027Prematurity, ELBW, RDS, ventilation, LOSLAMBDiedIndia
8asahiiMBlood98027Prematurity, ELBW, RDS, CPAP, LOSLAMBDiedIndia
11asahiiFBlood90030Prematurity, ELBW, LOSLAMBDiedIndia
Vashishtha et al. (2012)5Trichosporon spp.n/aBlood2890TermMSAF, PNA, gastrointestinal bleedingAMBDiedIndia
7Trichosporon spp.n/aBlood155031SGA with RDS (HMD), mechanical ventilationAMBDiedIndia
n/aasahiin/aBlood123528AGA, PNA, PPROM, RDSAMBDiedIndia
11Trichosporon spp.n/aBlood172034SGA, BOH. PPROM, NECAMBAliveIndia
21Trichosporon spp.n/aBlood108029SGA, PNA, PPROM, mechanical ventilationAMBDiedIndia
n/aasahiin/aBlood125032SGA, PNA, PPROM, RDS, mechanical ventilation, early onset sepsisAMBDiedIndia
n/aasahiin/aBlood120035SGA, polycythemia, sepsisAMBDiedIndia
n/aasahiin/aBlood2400TermSGA, PNA, sepsis AMBAliveIndia
Pereira et al. (2009)n/aasahiiMBlood81529RDS, mechanical ventilationn/aDiedBrazil
Chagas-Neto et al. (2009)16asahiiFBloodn/an/aPrematurityAMBDiedBrazil
84asahiiMBloodn/an/aPremature birth, enterectomyFLC+AMBAliveBrazil
Tellez-Castillo et al. (2008)n/aasahiin/aEndovascular catheter, tube68524Prematurity, sepsis, mechanical ventilationn/aDiedSpain
Maheshwari et al. (2004)26asahiiFBlood 73724RDS, mechanical ventilation, PDA, sepsisAMB + 5-FCAliveUSA
Yildiran et al. (2003)21asahiiFBlood, urine105027Prematurity, RDS, LOSAMBAliveTurkey
Salazar et al. (2002)15beigeliiMBlood, tracheal aspirate96027RDS, mechanical ventilation, sepsisAMBDiedUSA
17asahiiMPeritoneal fluid, blood, urine 72024RDS, mechanical ventilation, PPROMAMBDiedUSA
Panagopoulou et al. (2002)6asahiiFBlood89026RDS, LOSAMBAliveGreece
Sweet et al. (1998)16beigeliiFTracheal aspirate, peritoneal fluid, skin, urine95025RDS, PPROMLAMBAliveUnited Kingdom
Yoss et al. (1997)10beigeliiMBlood, umbilical catheter, tracheal aspirate53023RDS, sepsis, mechanical ventilationAMBDiedUSA
10beigeliiFUrine, tracheal aspirate, umbilical catheter54523RDS, mechanical ventilation, sepsisAMBDiedUSA
Abbreviations for Table 1. ELBW: Extremely low birth weight, RDS: Respiratory distress syndrome, LOS: Late onset sepsis, CPAP: Continuous positive airway pressure, MSAF: Meconium-stained amniotic fluid, PNA: Perinatal asphyxia, SGA: Small for gestational age, HMD: Hyaline membrane disease, AGA: Appropriate for gestational age, PPROM: Prolonged Premature Rupture of the Membranes, NEC: Necrotizing enterocolitis, BOH: Bad Obstetric History, PDA: Patent Ductus Arteriosus, LAMB: Liposomal Amphotericin B, AMB: Amphotericin B, FLC: Fluconazole, 5-FC: Flucytosine, M: Male, F: Female, n/a: not available, USA: United States of America.
Table 2. Characteristics of Invasive Trichosporon Infections (ITI) in pediatric patients with malignant and/or hematologic diseases.
Table 2. Characteristics of Invasive Trichosporon Infections (ITI) in pediatric patients with malignant and/or hematologic diseases.
Study (Year)Sex, Age (yrs)Underlying DiseaseANC<500Site of IsolationAntifungal ProphylaxisEmpirical Antifungal TreatmentTreatmentOutcomeCountry
Noni et al. (2020) F, 2.5Yolk sac tumorn/aBloodn/an/an/an/aGreece
M, 14Relapsed ALL after BMTn/aBloodn/an/an/an/aGreece
F, 10ALLn/aPleural fluidn/an/an/an/aGreece
n/a, 10Blackfan-Diamondn/aBlood, Bronchial secretionn/an/an/an/aGreece
Raju et al. (2019)M, 1WilmsYESBloodn/an/aVRCAliveIndia
Galligan et al. (2018)M,18Relapsed ALLn/aBlood, SkinMCFAMB, VRCVRCDied of ALLUSA
Lee Yuexian et al. (2017) F, 4Aplastic anemiaYESSkinCASLAMBVRCAliveSingapore
Nguyen et al. (2017)M, 10High-risk ALLYESLung, heart, kidney, spleen, lymph nodesMFGLAMBVRCDiedUSA
Foster et al. (2016)M, 10ALLYESBlood, lungMFGLAMBLAMB, VRCDiedUSA
F, 15ALLYESSkinMFGLAMBLAMB, VRCAliveUSA
F, 8ALLYESSkinMFGLAMB, VCZLAMB, VRCAliveUSA
Maxfield et al. (2015)F, 3ALLn/aBlood, Urine, Skinn/aVCZ, MCFLAMB, VRC Died of other cause USA
Oh et al. (2015)M, 3Mixed ALL/AMLYESSkinn/aMCFAMB, POSAliveUSA
Tanyildiz et al. (2015)M, 2LCHYESBloodn/aLAMBVRCAliveTurkey
F, 12Secondary AMLYESBloodn/aLAMBVRCAliveTurkey
Karapinar et al. (2014) F,16Aplastic anemiaYESBloodn/aCASVRCDiedTurkey
F, 5ALLYESBloodn/aCASVRCAliveTurkey
Agarwal and Joyce (2014)n/a, 12AMLYESBloodFLCn/an/aDiedUSA
n/a, 12AMLYESBloodCASn/an/aDiedUSA
n/a, 12AMLYESUrineMFGn/an/an/aUSA
n/a, 12AMLYESUrineVCZ, MFGn/an/an/aUSA
n/a, 13AMLYESBloodVCZn/an/aDiedUSA
n/a, 14AMLYESBloodMFGn/an/an/aUSA
Parlakay et al. (2013)M, 16Ewingn/aBlood, Conchae, nosen/aLAMB, CAS, LAMBDiedTurkey
Kudo et al. (2011) F, 0.4AMLYESBloodAMBMFGVCZAliveJapan
Thibeault et al. (2008) M, 11ALLYESBlood, liver, urinen/aL-AMBVCZDiedCanada
Tsuji et al. (2008) M,16ALLNOBlood, urineMFGVRCVCZDied of other causeJapan
Hosoki et al. (2008) M, 18MDSn/aBloodAMB, ITCLAMB, ITCLAMB, ITCDied of other causeJapan
Ghiasian et al. (2006) F, 11Aplastic anemiaYESBlood, sputum, oral lesionsn/aAMBAMBDiedIran
Antachopoulos et al. (2005) M, 13ALLYESBlood, BALAMBLAMBLAMB, VCZDied of other causeGreece
Meyer et al. (2002) n/a, 13Mixed ALL/AMLYESBlood, livern/aAMB ITCAliveFrance
Itoh et al. (1996)F, 5ALLYESBlood, skinn/an/aMFGDiedJapan
Abbreviations for Table 2: AMB: Amphotericin B, LAMB: Liposomal Amphotericin B, AFG: Anidulafungin, CAS: Caspofungin, 5FC: Flucytosine, FLC: Fluconazole, ITC: Itraconazole, MFG: Micafungin, POS: Posaconazole, VRC: Voriconazole, ALL: Acute Lymphoblastic Leukemia, AML: Acute Myeloid Leukemia, n/a: not available, M: Male, F: Female, USA: United States of America, BMT: Bone Marrow Transplantation, LCH: Langerhans Cell Histiocytosis, BAL: Bronchoalveolar Lavage.
Table 3. MICs (μg/mL) of antifungal agents for T. asahii isolates in studies with pediatric malignant and/or hematologic disorders.
Table 3. MICs (μg/mL) of antifungal agents for T. asahii isolates in studies with pediatric malignant and/or hematologic disorders.
Study (Year)SpeciesAMPB5-FCFluconazoleItraconazoleVoriconazolePosaconazoleCaspofunginMicafunginAnidulafungin
Noni et al. (2020) Yolk sac 0.125840.030.010.031888
Relapsed ALL after BMT8860.0310.0310.251688
ALL18320.060.060.125488
Blackfan-Diamond681640.190.031888
Raju et al. (2019)Wilmssensn/asensn/a0.06n/an/an/an/a
Galligan et al. (2018)Relapsed ALLn/an/an/an/an/an/an/an/an/a
Lee Yuexian et al. (2017) Aplastic anemian/an/an/an/an/an/an/an/an/a
Nguyen et al. (2017)High-risk ALLn/an/an/an/a≤0.03n/an/an/an/a
Foster et al. (2016)ALL2n/a0.50.5≤0.030.06>8>8>8
ALL1n/a40.50.1250.25>8>8>8
ALL1n/a20.50.060.125≥8≥8>8
Maxfield et al. (2015)ALLn/an/an/an/an/an/an/an/an/a
Oh et al. (2015)Mixed ALL/AMLn/an/an/an/an/an/an/an/an/a
Tanyildiz et al. (2015)LCH1n/a0.500.1250.030.254n/a2
Secondary AML1n/a0.50.250.060.53n/a3
Karapinar et al. (2014) Aplastic anemia1.5n/a30.0320.094n/a>32n/an/a
ALL0.008n/a0.0230.250.023n/a>32n/an/a
Agarwal and Joyce (2014)AMLn/an/an/an/an/an/an/an/an/a
AMLn/an/an/an/an/an/an/an/an/a
AMLn/an/an/an/an/an/an/an/an/a
AMLn/an/an/an/an/an/an/an/an/a
AMLn/an/an/an/an/an/an/an/an/a
AMLn/an/an/an/an/an/an/an/an/a
Parlakay et al. (2013)Ewingn/an/a4n/a0.03n/an/an/an/a
Kudo et al. (2011) AML2>64410.125n/an/a>16n/a
Thibeault et al. (2008) ALL8n/a1n/a0.03n/a>8n/an/a
Tsuji et al. (2008) ALL0.5n/a10.250.25n/a >16n/a
Hosoki et al. (2008) MDS2>128>1282 ≥32
Ghiasian et al. (2006) Aplastic anemian/an/an/an/an/an/an/an/an/a
Antachopoulos et al. (2005) ALL0.25n/a40.50.1250.5n/an/an/a
Meyer et al. (2002) Mixed ALL/AML0.032n/a22n/an/an/an/an/a
Itoh et al. (1996)ALL0.25n/an/an/an/an/an/an/an/a
Median MIC (pediatric studies) 183.50.3750.060.187888
Abbreviations for Table 3: AMP: Amphotericin B, 5-FC: Flucytosine, ALL: Acute Lymphoblastic Leukemia, AML: Acute Myeloid Leukemia, n/a: Not available, Sens: Sensitive, MIC: Minimal Inhibitory Concentration.
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Kourti, M.; Roilides, E. Invasive Trichosporonosis in Neonates and Pediatric Patients with Malignancies or Hematologic Disorders. Pathogens 2022, 11, 242. https://doi.org/10.3390/pathogens11020242

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Kourti M, Roilides E. Invasive Trichosporonosis in Neonates and Pediatric Patients with Malignancies or Hematologic Disorders. Pathogens. 2022; 11(2):242. https://doi.org/10.3390/pathogens11020242

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Kourti, Maria, and Emmanuel Roilides. 2022. "Invasive Trichosporonosis in Neonates and Pediatric Patients with Malignancies or Hematologic Disorders" Pathogens 11, no. 2: 242. https://doi.org/10.3390/pathogens11020242

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Kourti, M., & Roilides, E. (2022). Invasive Trichosporonosis in Neonates and Pediatric Patients with Malignancies or Hematologic Disorders. Pathogens, 11(2), 242. https://doi.org/10.3390/pathogens11020242

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