Candida lusitaniae Fungemia in Children: A multicenter case series of emerging pathogen.

Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play.

Candida lusitaniae fungemia is a serious infection rarely reported in children. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents. The higher rate of infection in recent years is in need of further investigation.

Scedosporium species and Lomentospora prolificans fungaemia is uniformly fatal in patients with haematological malignancy.

Scedosporium and Lomentospora species are environmental moulds that are virulent in immunocompromised hosts and rarely cause bloodstream infection (BSI). Patients with Scedosporium and Lomentospora species BSI were identified by the state public laboratory service in Queensland, Australia, over a 20-year period. Twenty-two incident episodes occurred among 21 residents; one patient had a second episode 321 days following the first. Of these, 18 were Lomentospora prolificans, three were Scedosporium apiospermum complex and one was a nonspeciated Scedosporium species. Seventeen (81%) patients died during their index admission, and all-cause mortality at 30, 90 and 365 days was 73%, 82% and 91% respectively. All 20 patients with haematological malignancy died within 365 days of follow-up with a median time to death of 9 days (interquartile range, 6-20 days) following diagnoses of BSI.

Comparison of the characteristics of patients with invasive infections and noninvasive infections caused by Trichosporon asahii.

We performed retrospective study to identify the characteristics of invasive Trichosporon asahii infection. A total of 102 patients with T. asahii were identified including 18 (18%) with invasive infection. Invasive infection was associated with indwelling central venous catheter (94% vs 54%, P = .001), prior antifungal agent use (50% vs 18%, P = .01), hematologic malignancy (33% vs 7%, P = .006), and end-stage renal disease (28% vs 7%, P = .02). Patients with invasive infections had higher in-hospital mortality than patients with noninvasive infections (61% vs 27%, P = .006). Those with the above risk factors should be monitored for the development of invasive T. asahii infection. LAY SUMMARY: Patients with indwelling central venous catheter, prior antifungal agent use, hematologic malignancy, and end-stage renal disease were associated with invasive Trichosporon asahii infection. Patients with invasive infections had higher in-hospital mortality than patients without invasive infection.

Mixed fungaemia: an 18-year report from a tertiary-care university hospital and a systematic review.

BACKGROUND: While fungaemia caused by two or more different species of yeasts (mixed fungaemia, MF) is infrequent, it might be underestimated. AIMS: This study aimed to determine the incidence of MF, clinical characteristics of the patients, and antifungal susceptibility profiles of the isolates with a systematic review of the literature. SOURCES: Data sources were PubMed and Scopus. STUDY ELIGIBILITY CRITERIA: Studies reporting ten or more mixed fungaemia episodes. CONTENT: Study included MF episodes in adults between January 2000 and August 2018 in Hacettepe University Hospitals, Turkey. The isolation, identification and antifungal susceptibility testing (AFST) of the isolates were by standard mycological methods. Patient data were obtained retrospectively. Literature search was performed using relevant keywords according to PRISMA systematic review guidelines. A total of 32 patients with 33 MF episodes were identified. Among all fungaemia episodes, MF incidence was 3.7% (33/883). All patients had one or more underlying disorders among which solid-organ cancer (50.0%, 16/32) was the most common. Overall mortality was 51.5% (17/33). The most preferred antifungal agents for initial treatment were fluconazole (48.5%, 16/33) and echinocandins (39.4%, 13/33). Fluconazole susceptible-dose-dependent (S-DD) or -resistant Candida species were detected in 15 episodes, and an isolate of C. parapsilosis was classified as S-DD by AFST. All Candida isolates were susceptible to echinocandins. Non-candida yeasts with intrinsic resistance/reduced susceptibility to both echinocandins and fluconazole were detected in two episodes. Systematic review of the literature revealed 24 studies that reported more than ten MF episodes. Methodology was variable. Improvement of detection rates was reported when chromogenic agars were used. Most studies underlined detection of isolates with reduced susceptibility. IMPLICATIONS: Although rare, the MF rate is affected by the detection methods, which have improved in recent years. Fluconazole and echinocandins were used for initial treatment in accordance with the current guideline recommendations; however, isolates non-susceptible to both were detected. Detection of a mixed infection offers an opportunity for optimum treatment.

Fungaemia due to rare yeasts in a tertiary care university centre within 18 years.

BACKGROUND: Fungaemia due to rare yeasts has been recognised as an emerging, clinically relevant, but less investigated condition. Intrinsic resistance or reduced susceptibility of these species to echinocandins or fluconazole remains as a challenge in empirical treatment. OBJECTIVES: To describe the clinical characteristics, administered antifungal agents, outcomes of patients with rare yeasts other than Candida (RY-OTC) fungaemia and determine the antifungal susceptibility profiles of the isolates. PATIENTS AND METHODS: RY-OTC fungaemia between January-2001 and December-2018 were retrospectively evaluated. Antifungal susceptibility tests were performed according to CLSI M27-A3. RESULTS: We identified 19 patients with fungaemia due to 20 RY-OTC (8 Trichosporon asahii, 4 Cryptococcus neoformans, 4 Saprochaete capitata, 3 Rhodotorula mucilaginosa, 1 Trichosporon mucoides) with an incidence of 2.2% among 859 fungaemia episodes. Haematological malignancy was the most common (42%) underlying disorder. In 6 patients, RY-OTC fungaemia developed as breakthrough infection while receiving echinocandins, amphotericin B or fluconazole. Amphotericin B, fluconazole or voriconazole were the drugs of choice for the initial treatment of breakthrough fungaemia. Among patients without previous exposure to antifungals, the most common empirical treatment was an echinocandin (50%), followed by fluconazole (42%) and amphotericin B (8%). Overall mortality was 47%. Worse outcome was most common among patients receiving echinocandins (83% vs 25%, P < .05). Voriconazole and posaconazole showed the highest in vitro activity against all the isolates tested. Amphotericin B MICs were relatively higher and the degree of activity of fluconazole and itraconazole was variable. CONCLUSIONS: Early recognition of RY-OTC and knowledge about their susceptibility patterns remain crucial in initial treatment pending susceptibility data of isolates.

The clinical characteristics of adult cryptococcal meningitis patients who died within one year of treatment with a focus on those with early mortality.

Cryptococcal meningitis (CM) is a serious infectious disease of the central nervous system, and associated brain injuries can be found in the very early stage of disease. In this study, 92 adult CM patients (59 men, 33 women; median age 54.66 years, range 20-86 years) were enrolled, and their clinical, laboratory, neuroimaging features and therapeutic outcomes were analyzed. Two main clinical comparative analyses of the clinical characteristics and laboratory and neuroimaging features were made in this study. The first compared clinical differences between the survivors and non-survivors of all enrolled patients, and the second compared differences between the following three groups: Group I, the patients who died within 14 days of initiating treatment; Group II, the patients who died within 15 days to 1 year of initiating treatment, and Group III, the patients who survived for more than 1 year after initiating treatment. Prognostic factors including initial altered consciousness, increased cerebrospinal fluid (CSF) lactate level and the presence of cryptococcemia were significantly different between the different groups. The patients with early mortality had a higher CSF lactate level and higher rate of cryptococcemia. The presence of cryptococcemia was an important prognostic factor, and the patients with cryptococcemia had a higher incidence of positive CSF India ink stain. Further large-scale studies are needed to delineate the clinical and laboratory features of CM patients with early mortality.

Fungaemia in haematological malignancies: SEIFEM-2015 survey.

BACKGROUND: Fungal infections are still a relevant challenge for clinicians involved in the cure of patients with cancer. We retrospectively reviewed charts of hospitalized patients with haematological malignancies (HMs), in which a documented fungaemia was diagnosed between January 2011 and December 2015 at 28 adult and 6 paediatric Italian Hematology Departments. METHODS: During the study period, we recorded 215 fungal bloodstream infections (BSI). Microbiological analyses documented that BSI was due to moulds in 17 patients (8%) and yeasts in 198 patients (92%), being Candida spp identified in 174 patients (81%). RESULTS: Mortality rates were 70% and 39% for mould and yeast infections, respectively. Infection was the main cause of death in 53% of the mould and 18% of the yeast groups. At the multivariate analysis, ECOG ≥ 2 and septic shock were significantly associated with increased mortality, and removal of central venous catheter (CVC) survival was found to be protective. When considering patients with candidemia only, ECOG ≥ 2 and removal of CVC were statistically associated with overall mortality. CONCLUSIONS: Although candidemia represents a group of BSI with a good prognosis, its risk factors largely overlap with those identified for all fungaemias, even though the candidemia-related mortality is lower when compared to other fungal BSI. Management of fungal BSI is still a complex issue, in which both patients and disease characteristics should be focused to address a personalized approach.

CYP51 as drug targets for fungi and protozoan parasites: past, present and future.

The efficiency of treatment of human infections with the unicellular eukaryotic pathogens such as fungi and protozoa remains deeply unsatisfactory. For example, the mortality rates from nosocomial fungemia in critically ill, immunosuppressed or post-cancer patients often exceed 50%. A set of six systemic clinical azoles [sterol 14α-demethylase (CYP51) inhibitors] represents the first-line antifungal treatment. All these drugs were discovered empirically, by monitoring their effects on fungal cell growth, though it had been proven that they kill fungal cells by blocking the biosynthesis of ergosterol in fungi at the stage of 14α-demethylation of the sterol nucleus. This review briefs the history of antifungal azoles, outlines the situation with the current clinical azole-based drugs, describes the attempts of their repurposing for treatment of human infections with the protozoan parasites that, similar to fungi, also produce endogenous sterols, and discusses the most recently acquired knowledge on the CYP51 structure/function and inhibition. It is our belief that this information should be helpful in shifting from the traditional phenotypic screening to the actual target-driven drug discovery paradigm, which will rationalize and substantially accelerate the development of new, more efficient and pathogen-oriented CYP51 inhibitors.

Management of an Outbreak of Exophiala dermatitidis Bloodstream Infections at an Outpatient Oncology Clinic.

We report the presentation and management of 17 cases of Exophiala dermatitidis and Rhodotorula mucilaginosa bloodstream infections caused by a compounded parenteral medication at an oncology clinic. Twelve patients were asymptomatic. All central venous catheters were removed and antifungal therapy, primarily voriconazole, was administered to patients. Three patients died.

Predisposing factors and outcome of uncommon yeast species-related fungaemia based on an exhaustive surveillance programme (2002-14).

Objectives: Using registry data to compare fungaemia caused by uncommon yeast species (UYS; i.e. other than Candida albicans , Candida glabrata , Candida parapsilosis , Candida tropicalis and Candida krusei ) and C. albicans -related fungaemia can reveal specific predisposing factors of UYS with potential impact on treatment strategies. Methods: We analysed 338 episodes of UYS fungaemia prospectively collected from 27 hospitals (Paris, France; 1 October 2002-31 December 2014) and compared these with 1998 single episodes of C. albicans fungaemia using univariate and multivariate analyses. Results: The proportion of UYS fungaemia was stable over time. Thirty-five different species were identified (27 ascomycetes, 8 basidiomycetes), 11 had caspofungin MIC 50 >0.25 mg/L and 15 fluconazole MIC 50 >4 mg/L. Haematological malignancies [OR=2.39 (95% CI 1.79-3.18)] and prior exposure to antifungal drugs [OR=1.87 (1.30-2.69)] were independent predisposing factors for UYS infections upon multivariate analysis. However, when considering the genus/species complex level, only infections due to Candida kefyr -related species [OR=4.01 (2.42-6.64)] and to Trichosporon spp. [OR=5.38 (1.72-16.81)] remained associated with haematological malignancies, those due to the GEOTRICHUM group with acute leukaemia [OR=61.29 (19.23-195.36)], and infections with Trichosporon spp. or the GEOTRICHUM group with prior exposure to caspofungin [OR=15.67 (3.62-67.80) and OR=13.17 (3.33-52.03), respectively] but not to fluconazole. The global mortality at day 30 for UYS was similar to that for C. albicans (35.4%, and 39.9%, respectively), but very divergent results were observed according to the specific UYS. Conclusions: UYS encompass a high diversity of species, each with its own behaviour and predisposing factors for human infections. This variety makes it important to rapidly identify an isolate to the species level in order to optimize antifungal treatment.

Candida infections in paediatrics: Results from a prospective single-centre study in a tertiary care children's hospital.

To describe the epidemiology of invasive Candida infection in a tertiary care paediatric hospital. Prospective single-centre survey on all Candida strains isolated from normally sterile fluids and urines in the period 2005-2015 . A total of 299 ICI were documented in 262 patients. Urinary tract infection represented the most frequent diagnosis (62%), followed by fungaemia (34%) and peritonitis (4%). Fungaemia was most frequent in children with cancer (59%) or in low birth weight neonates (61%), while urinary tract infections were more frequent in patients with urinary tract malformation. C.albicans was the most frequently isolated species (60%) compared with C. non-albicans, but differences were present according to the site of isolation and underlying conditions. Overall 90-day mortality was 7%, 13% in fungaemias, 8% in peritonitis and 2% in urinary tract infections. The rates of invasive Candida infection increased during the study period. Invasive Candida infection is diagnosed with increasing frequency in children. Site of isolation and aetiology are frequently related with the presence of underlying, favouring conditions. Mortality was not negligible, especially in the presence of more invasive infections and specific underlying conditions.

Saprochaete capitata as an emerging fungus among patients with haematological malignencies.

Saprochaete capitata is a very rare pathogen that causes invasive disease particularly in patients with haematological malignancies. We recognised a clustering of S. capitata fungaemia in recent years. So, we report our 6-year surveillance study of fungaemia among patients with haematological malignancies and haematopoietic stem cell transplant. We performed a retrospective and observational study. Hospitalised patients aged >18 years with haematological malignancies were included in the study. A total of 51 fungaemia episodes of 47 patients were analysed. The characteristics of fungaemia in patients with S. capitata compared to patients with candidemia. Median duration of neutropenia was 21.5 days in patients with S. capitata fungaemia, whereas this duration was significantly shorter in patients with candidemia (8 days). Interval between first and last positive culture was significantly longer in patients with S. capitata fungaemia (P < 0.05). Previous use of caspofungin was significantly more common in patients with S. capitata fungaemia. Thirty-day mortality was found 40% for patients with candidemia, whereas it was 39% for patients with S. capitata. In conclusion, despite its limitations this study showed that a novel and more resistant yeast-like pathogen become prevalent due to use of caspofungin in patients with long-lasting neutropenia which was the most noteworthy finding of this 6-year surveillance study.

Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031).

BACKGROUND: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. METHODS: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. RESULTS: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.

Epidemiology and outcomes of invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients in the era of antifungal prophylaxis: a single-centre study with focus on emerging pathogens.

With increased use of expanded-spectrum triazoles for antifungal prophylaxis, the epidemiology of invasive fungal infections (IFIs) after allogeneic haematopoietic stem cell transplantation (HSCT) continues to evolve. To define the contemporary epidemiology of IFIs in this population, we reviewed all European Organization for Research and Treatment of Cancer-Mycoses Study Group proven and probable IFIs in adults transplanted from 2002 to 2011 and determined the incidence and risk factors for IFI and post-IFI mortality. All patients received antifungal prophylaxis. Fifty-three (14%) of 378 allogeneic HSCT recipients developed an IFI. There were 62 IFI episodes, of which aspergillosis (n = 31; 50%) and candidaemia (n = 15; 24%) were most common. Sixteen episodes (26%) were caused by other fungi, including Mucorales (n = 6; 10%) and the following uncommon pathogens: Trichosporon asahii, Arthrographis sp., Cladosporium sp., Geosmithia argillacea and Hormographiella aspergillata. Independent IFI risk factors were hospitalisation in an intensive care unit [ICU; odds ratio (OR) = 6.0], graft-versus-host disease (OR = 5.3), central venous catheter use (OR = 5.2) and hypoalbuminaemia (OR = 0.3 g(-1)  dl(-1) increase in albumin). The 90-day mortality rate after IFI was 57%. Non-cytomegalovirus systemic viral co-infection (OR = 3.5) and stay in an ICU (OR = 2.9) were independent risk factors for death. Despite antifungal prophylaxis, IFIs remain common after allogeneic HSCT and previously uncommon pathogens are emerging.

Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality.

The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes; mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%); antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p <0.01); 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19-275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4%; HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected diverse patient groups, including non-immunocompromised hosts and those outside traditional risk groups; therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required.

Microbiologically documented fungal infections in pediatric patients with acute myeloid leukemia: 12.5-year experience at a single institution.

The primary objective of this study was to determine the incidence and types of microbiologically documented fungal infections in 56 children with acute myeloid leukemia admitted to Wolfson Children's Hospital. The secondary objective was to determine the factors that may affect the treatment and outcome of these infections, such as antifungal prophylaxis, absolute neutrophil count, age, and phase of therapy. Medical records were reviewed from January 1, 2000 to July 31, 2012. Over the 12.5-year study period, there were 11 patients with 25 episodes of fungal infections. Adolescents with acute myeloid leukemia (13 to 18 y old) represented 48% of the population. Children less than 3 years of age and between 3 and 12 years of age represented one quarter each. None of the patients less than 3 years of age developed fungal infections, whereas 64% of the adolescents did (P=0.01). Blood-borne infections were the most common site of infection (44%). Eighty-four percent of infections occurred in neutropenic patients. The mortality rate in the overall cohort was 28%. Patients with fungal infections had increased mortality rate of 55%. Overall candidiasis and aspergillosis were the major pathogens (28% each), although there have been no occurrences of Aspergillus sp. since 2005. On the basis of the results of our study, it would be prudent to provide antifungal coverage for both these pathogens, such as with voriconazole or echinocandins over fluconazole.

Second- versus first-generation azoles for antifungal prophylaxis in hematology patients: a systematic review and meta-analysis.

Second-generation azoles may be more effective than first-generation azoles in the prevention of fungal infections in hematology patients. We performed a systematic review with meta-analysis of randomized controlled trials comparing second- with first-generation azoles in hematology patients with respect to proven or probable invasive fungal infections, invasive aspergillosis, receipt of empirical antifungal therapy, overall mortality, and withdrawal from the studies due to the development of adverse effects. We searched the Medline, Embase, and Cochrane Registry of Controlled Trials electronic databases as well as conference proceedings from 2002 to 2012 for randomized controlled trials comparing second-generation azoles (voriconazole, posaconazole) versus first-generation azoles (fluconazole, itraconazole). Treatment effect measures for all outcomes were expressed as odds ratio with 95 % confidence interval. Meta-analysis was performed using Review Manager, version 5.1. Data from four randomized clinical trials representing a large population of patients demonstrated that antifungal prophylaxis with second-generation azoles reduces proven or probable invasive fungal infections, invasive aspergillosis, and receipt of empirical antifungal therapy in high-risk hematology patients, while there were no differences between second- and first-generation azoles with regard to overall mortality and patients or withdrawal from the studies due to the development of adverse effects. In conclusion, antifungal prophylaxis with second-generation azoles can significantly reduce the incidence of invasive fungal infections and invasive aspergillosis but with no risk of an increase in adverse events.

Risk factors associated with liver injury and impact of liver injury on transplantation-related mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation.

In adults, hepatic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with significant morbidity and transplantation-related mortality (TRM). However, there is a paucity of parallel data on the incidence of, and risk factors for, liver injury (LI) and the impact of LI on TRM in pediatric allo-HSCT recipients. We compared total bilirubin, direct bilirubin, and alanine aminotransferase values before allo-HSCT and at 1 month, day +100, and 12 months after allo-HSCT in 248 patients who received either a myeloablative conditioning (MAC) regimen (n = 109) or a reduced-toxicity/reduced-intensity conditioning (RTC/RIC) regimen (n = 139). LI was defined as grade ≥ 2 hyperbilirubinemia according to the National Cancer Institute's Common Terminology Criteria for Adverse Events 3.0/4.0 (total bilirubin, >1.95 mg/dL, 1.5 times above the upper limit of normal for our laboratory). Univariate and multivariate logistic regression models were used to identify risk factors for LI and TRM. The incidence of LI at 1 month after allo-HSCT was 14.1%. The median bilirubin level was 3.5 mg/dL (range, 1.97 to 32.2 mg/dL). Only LI as defined by total bilirubin level, but not by direct bilirubin or alanine aminotransferase level, was found to be a significant predictor for TRM. The 1-year TRM was 60.7% (95% confidence interval, 42.6% to 78.7%) in patients with LI at 1 month after allo-HSCT, compared with 14.6% (95% confidence interval, 9.9% to 19.4%) (P < .0001) in patients those who did not have liver injury. Multivariate analysis identified age (P = .03), total body irradiation (P = .007), bacterial bloodstream infection (BBSI) (P = .001), and invasive fungal infection (IFI) (P = .002) as significant risk factors for developing LI at 1 month. On multivariate analysis for risk factors for TRM, only LI at 1 month after allo-HSCT (P < .0001), primary graft failure (P = .001), BBSI (P = .003), and systemic viral infection (P = .04) were identified as significant risk factors for TRM. LI before allo-HSCT conditioning was not associated with higher TRM. Although the incidence of LI in pediatric allo-HSCT recipients is low, LI is associated with very high TRM. BBSI and IFI are the primary risk factors for LI.