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Revista Iberoamericana de Micología Analysis of risk factors and prognosis of fluconazole-resistant Candida tropical...
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Analysis of risk factors and prognosis of fluconazole-resistant Candida tropicalis bloodstream infection

Análisis de los factores de riesgo y pronóstico en la candidemia por Candida tropicalis resistente al fluconazol
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Fei Wanga, Yake Yaob, Qing Yangc, XueMei Lind, Yihua Zhengd, Hua Zhoub, Qin Huange,
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a Department of Respiratory Medicine, Zhejiang Hospital, Hangzhou, China
b Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, China
c Department of Clinical Laboratory, The First Affiliated Hospital, Zhejiang University School of Medicine, China
d Department of Respiratory and Critical Care Medicine, Jiangshan People's Hospital, China
e Zhejiang Hospital Infection Department, Zhejiang Hospital, Hangzhou, China
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Table 1. Single factor analysis of risk factors for bloodstream infection with fluconazole resistant C. tropicalis.
Tablas
Table 2. Multivariate binary logistic analysis of risk factors in fluconazole resistant C. tropicalis bloodstream infection.
Tablas
Table 3. Univariate analysis of risk factors of death in patients with C. tropicalis bloodstream infection.
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Table 4. Cox regression analysis of correlation factors for mortality of C. tropicalis bloodstream infection.
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Abstract
Background

In China, the isolation rate of fluconazole-resistant isolates of Candida tropicalis, together with fatality in cases of bloodstream infections due to this yeast, have increased annually.

Aims

This study investigates the clinical characteristics, risk factors, and prognostic factors of fluconazole-resistant C. tropicalis bloodstream infections (BSI).

Methods

A retrospective study analyzed clinical data of patients with C. tropicalis BSI from July 2013 to June 2019, focusing on clinical characteristics, risk factors, treatment regimens, and prognosis. Univariate analysis of risk factors and prognosis was conducted using χ2 test or Fisher's exact tests. Binary logistic regression model for risk factors, and Cox regression method for prognosis, were used for multivariate analysis.

Results

The study enrolled 100 patients with C. tropicalis BSI, including 44 fluconazole-resistant and 56 fluconazole-sensitive cases; 64 patients were cured and 36 died, resulting in a mortality rate of 36%. Logistic regression analysis identified exposure to azole antifungal agents during the 2 weeks prior to the onset of the BSI as a risk factor for fluconazole resistance. Cox regression analysis showed that hematological malignancy, fluconazole-resistant strains, indwelling catheters, and chronic obstructive pulmonary disease were independent risk factors for patient mortality. Conversely, targeted therapy with sensitive antifungal agents and removal of drainage tubes were protective factors for survival.

Conclusions

Azole exposure led to the development of fluconazole resistance in C. tropicalis BSI; hematologic malignancies, azole resistance, chronic obstructive pulmonary disease and having intravenous catheters increased mortality rate. The use of echinocandins or amphotericin B and catheter removal improved outcomes, underscoring the need for early resistance detection and targeted treatment.

Keywords:
Fluconazole-resistant
Candida tropicalis
Risk factors
Prognosis
Resumen
Antecedentes

En China, el aislamiento de cepas de Candida tropicalis resistentes al fluconazol ha aumentado anualmente, así como la mortalidad en casos de infecciones del torrente sanguíneo causadas por esta levadura.

Objetivos

Este estudio investiga las características clínicas, los factores de riesgo y los factores pronósticos de candidemias debidas a aislamientos de C. tropicalis resistentes al fluconazol.

Métodos

Entre julio de 2013 y junio de 2019 se realizó un estudio retrospectivo en el que se analizaron los datos clínicos de pacientes con candidemia por C. tropicalis, con especial relevancia en las características clínicas, los factores de riesgo, los regímenes de tratamiento y el pronóstico. Se llevó a cabo un análisis univariante de los factores de riesgo y del pronóstico mediante la prueba χ2 o la prueba exacta de Fisher. Para el análisis multivariante se utilizó un modelo de regresión logística binaria para los factores de riesgo y el método de regresión de Cox para el pronóstico.

Resultados

En el estudio fueron incluidos 100 pacientes con candidemia por C. tropicalis, entre los que se encontraban 44 casos con resistencia al fluconazol y 56 sensibles al fluconazol. Sesenta y cuatro pacientes se curaron y 36 fallecieron, lo que supuso una tasa de mortalidad del 36%. Según el análisis de regresión logística, la exposición a agentes antifúngicos azólicos en las dos semanas previas a la aparición de la candidemia fue un factor de riesgo para desarrollar resistencia al fluconazol. El análisis de regresión de Cox mostró que la neoplasia hematológica maligna, las cepas resistentes al fluconazol, portar catéteres permanentes y la enfermedad pulmonar obstructiva crónica eran factores de riesgo independientes de mortalidad de los pacientes. Por el contrario, la terapia dirigida con los agentes antifúngicos adecuados y la retirada de los tubos de drenaje fueron medidas que incrementaron la supervivencia.

Conclusiones

La exposición a azolespuede provocar la aparición de resistencia al fluconazol en casos de candidemia por C. tropicalis; las neoplasias hematológicas, la resistencia a los azoles, la enfermedad pulmonar obstructiva crónica y la presencia de catéteres intravenosos aumentaron la tasa de mortalidad. El uso de equinocandinas o anfotericina B y la retirada del catéter mejoró el pronóstico, lo que subraya la necesidad de detectar precozmente la resistencia y aplicar un tratamiento específico.

Palabras clave:
Resistencia a fluconazol
Candida tropicalis
Factores de riesgo
Pronóstico
Texto completo

Candidemia, caused by Candida species, represents a life-threatening complication in immunocompromised and critically ill patients,18,22 with mortality rates exceeding 30% despite advances in antifungal therapies.16 While Candida albicans remains the most common etiological agent, non-C. albicans Candida species now account for nearly half of invasive candidiasis cases globally, reflecting shifting epidemiological trends driven by prolonged ICU stays, broad-spectrum antibiotic use, and immunosuppressive therapies.26 Among these emerging pathogens, Candida tropicalis has garnered significant clinical attention due to its rising incidence, intrinsic resistance patterns, and disproportionately high mortality rates,3,8,13 particularly in subtropical and tropical regions.

Geographical disparities in Candida epidemiology further complicate management strategies. Surveillance data from Saudi Arabia found higher mortality in ICU-acquired C. albicans–candidemia, compared with cases due to non-C. albicans Candida species.2 In contrast, Thai studies revealed C. tropicalis was the dominant pathogen in bloodstream infections (BSI).23 The respiratory tract serves as a critical reservoir for C. tropicalis dissemination, particularly in patients with structural lung disease, prolonged mechanical ventilation, or compromised mucociliary clearance.29 This species exhibits unique pulmonary tropism through biofilm formation on endotracheal devices, enhanced epithelial adhesion via Als3 virulence factors, and immune evasion mechanisms mediated by β-glucan masking.12 According to the data from a surveillance study conducted to ascertain the degree of antifungal resistance in invasive candidiasis in China over the past 5 years, the fluconazole and voriconazole resistance rates of C. tropicalis increased from <8% in 2009–2010 to over 22% in 2013–2014.34

The World Helth Organization has recently defined C. tropicalis as a critical fungal pathogen, necessitating targeted research into geography-dependent virulence, rapid molecular diagnostics, and inhaled antifungal delivery systems.27 This study elucidates the epidemiological burden and prognostic impact of fluconazole-resistant C. tropicalis infections in a subtropical zone, aiming to inform regionally tailored prevention strategies and enhance awareness of this underrecognized threat in Zhejiang Province.

Materials and methodsPatients included

One hundred patients diagnosed with blood stream infection (BSI) caused by C. tropicalis through blood culture in the First Affiliated Hospital, Zhejiang University School of Medicine, from July 2013 to June 2019, were included. Inclusion criteria fulfilled the diagnostic criteria for invasive mycosis formulated by the European Cancer Treatment and Research Collaboration Group (EORTC/MSG) in 20084; C. tropicalis had to be isolated from blood culture, having the patient clinical signs and symptoms of BSI. The isolation of C. tropicalis from a blood culture likely contaminated, patients younger than 18 years old, or having no detailed clinical data were the exclusion criteria. If the patient had multiple positive blood cultures, only the first one was considered. Long-term glucocorticoid therapy was defined as prednisone ≥20mg/day for more than 7 days. Long-term immunosuppressive therapy was defined as using immunosuppressive agents for more than 2 weeks. Antibiotic exposure was defined as more than 5 days of antibiotic use within 2 weeks prior to the onset of the disease.

The records of all 100 patients were retrieved. Clinical data were collected including patients’ gender, age, check-in desk, hospitalized time, length of hospital stay, blood culture results, comorbidities, invasive operation, parenteral nutrition, the usage of antibiotics, long-term use of glucocorticoids and/or immune inhibitors, tumor chemotherapy, empirical antifungal therapy, target antifungal therapy and pathogenic microbiology tests. Risk factors and prognosis were analyzed. Hypoproteinemia is defined as serum albumin less than 30g/L11; agranulocytosis was defined as the absolute count of neutrophils in peripheral blood under 0.5×109cells/L30; and renal insufficiency was defined as glomerular filtration rate lower than 60ml/min/1.73m2.6

Blood culture and strain identification and susceptibility tests

Bact/Alert 3D full-automatic blood culture instrument and the corresponding Bact/Alert culture flask were used for blood culture. VITEK 2 compact was used to identify strains, and ATB-Fungus susceptibility kit was used for susceptibility testing. The above instruments and reagents were all products from bioMérieux. The results were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) standard M27, a method for testing the susceptibility to antifungal agents of yeasts that cause invasive fungal infections.15 Susceptibility to 5-fluorouracil, amphotericin B, micafungin, caspofungin, fluconazole, voriconazole and itraconazole were published by CLSI M27-S2.

Statistical methods

SPSS19.0 software was used for statistical analysis. Data conforming to a Normal distribution were represented by mean±standard deviation and t-test, while counting data were tested by chi-square test or two-sided Fisher exact probability test. Factors in univariate analysis (p<0.05) were included in logistic regression model for multivariate analysis. In order to perfect the analysis of the risk factors that may be related to the prognosis of the patients, Cox regression model was used for multi-factor analysis. p<0.05 was considered statistically significant.

ResultsDemographic and clinical characteristics of patients with C. tropicalis BSI

Of the 100 patients, 64 were male (64%), with an average age of 53.0±17.4 years. According to the results of the drug susceptibility test of C. tropicalis, 44 isolates were resistant to fluconazole. The comorbidities included hematological malignancy (40%), chronic obstructive pulmonary disease (36%), hypoalbuminemia (33%), agranulocytosis (29%), impairment of renal function (23%), solid organ transplantation (18%), solid organ tumor (16%), diabetes (15%).

Before the onset of C. tropical candidemia, eighty cases (80%) were treated with broad-spectrum antibiotics for at least 5 days, 64 cases (64%) had parenteral nutrition for at least 5 days, 45 cases (45%) were treated with chemotherapy, indwelling catheterization was present for at least 7 days in 34 cases (34%), glucocorticoids and/or immunosuppressive treatments were used in 32 cases (32%), mechanical ventilation was used in 30 cases (30%), ICU length-of-stay for 7 days or more occurred in 17 cases (17%), and hemodialysis was performed in 15 cases (15%) (Table 1).

Table 1.

Single factor analysis of risk factors for bloodstream infection with fluconazole resistant C. tropicalis.

Factors  Patients with fluconazole resistant C. tropicalisn=44 (%)  Patients with fluconazole sensitive C. tropicalisn=56 (%)  χ2  p-Values 
Age (mean±SD)  53.14±15.96  52.96±18.88    0.9615 
≥60 years old  16 (36.4)  19 (33.9)  0.064  0.8 
Male gender  28 (63.6)  36 (64.3)  0.005  0.946 
Underlying disease
Hematological malignancy  22 (50)  18 (32.1)  3.274  0.07 
Solid organ tumor  6 (13.6)  10 (17.9)  0.327  0.568 
Diabetes  6 (13.6)  9 (16.1)  0.115  0.735 
Renal insufficiency  7 (15.9)  16 (28.6)  2.231  0.135 
Solid organ transplantation  12 (27.3)  6 (10.7)  4.577  0.032 
Agranulocytosis  16 (36.4)  13 (23.2)  2.069  0.15 
Chronic obstructive pulmonary disease  14 (31.8)  22 (39.3)  0.596  0.44 
Hypoproteinemia  15 (34.1)  18 (32.1)  0.042  0.837 
Related treatment and others
Deep vein catheterization  16 (36.4)  28 (50)  1.860  0.173 
Indwelling gastric tube  10 (22.7)  18 (32.1)  1.084  0.298 
Indwelling catheter ≥7 days  14 (31.8)  20 (35.7)  0.167  0.683 
Mechanical ventilation  11 (25)  19 (33.9)  0.935  0.333 
Parenteral nutrition ≥5 days  28 (63.6)  36 (64.3)  0.005  0.946 
Indwelling cavity drainage tube  11 (25)  15 (26.8)  0.041  0.840 
Surgery  13 (29.5)  21 (37.5)  0.695  0.405 
Use of broad-spectrum antibiotics ≥5 days  38 (86.4)  42 (75)  1.989  0.158 
Hemodialysis  4 (9.1)  11 (19.6)  2.152  0.142 
Stay in hospital for more than 4 weeks  28 (63.6)  30 (53.6)  1.025  0.311 
Recent exposure to azoles ≥2 weeks  25 (56.8)  12 (21.4)  13.239  <0.001 
Long-term use of glucocorticoids and/or immunosuppressants  19 (43.2)  13 (23.2)  4.515  0.034 
Chemotherapy  25 (56.8)  20 (35.7)  4.434  0.035 

SD: standard deviation.

Fever was the most common clinical manifestation (91/100, 91%), accompanied by cough, sputum or shortness of breath in 42 cases (42%), disturbance of consciousness in 15 cases (15%), abdominal pain, diarrhea or gastrointestinal bleeding in 8 cases (8%), and shock in 8 cases (8%).

C. tropicalis was also recovered from other specimens than blood in 37 patients, including sputum (12 cases), ascites (7 cases), urine (7 cases), drainage fluid (3 cases), sputum+ascites (2 cases), drainage fluid+urine liquid (2 cases), sputum+urine (1 case), lumbar puncture fluid+disc necrosis (1 case), bile (1 case), bile+ascites (1 case). Twenty four patients had also bacteremia: Pseudomonas aeruginosa in 6 cases, Acinetobacter baumannii in 6 cases, Escherichia coli in 5 cases, Klebsiella pneumoniae in 5 cases, Enterococcus in 5 cases, Burkholderia in 2 cases, Staphylococcus aureus in one case, and Enterobacter aerogenes in one case. Four patients (4%) suffered other fungal BSI with the following species: Candida glabrata, Candida albicans, Candida famata, Candida glabrata+Candida krusei.

Risk factors of fluconazole resistant C. tropicalis BSI

Univariate analysis showed that solid organ transplantation, exposure to azole for weeks, long-term use of glucocorticoids and/or immunosuppressants, and having received chemotherapy were the risk factor associated to fluconazole resistant C. tropicalis BSI (p<0.05) (Table 1). According to the results obtained with the multivariate logistic analysis azole exposure (OR=5.725, p=0.001) was an independent risk factor for suffering a BSI with C. tropicalis–fluconazole resistant strains, while other factors were not statistically significant in multivariate analysis (Table 2).

Table 2.

Multivariate binary logistic analysis of risk factors in fluconazole resistant C. tropicalis bloodstream infection.

Factors  Regression coefficient(BStandard error(Sb)  Wald value  OR value (95% confidence interval)  p-Values 
Solid organ transplantation  0.406  0.643  0.398  1.5 (0.426, 5.286)  0.528 
Recent exposure to azoles ≥2 weeks  1.745  0.524  11.102  5.725 (2.051, 15.979)  0.001 
Long-term use of glucocorticoids and/or immunosuppressants  0.796  0.496  2.577  2.217 (0.839, 5.862)  0.108 
Chemotherapy  0.381  0.476  0.64  1.464 (0.576, 3.722)  0.424 
Antimicrobial treatment and prognosis in patients with C. tropicalis BSI

In this group, isolates of C. tropicalis obtained from patients were all sensitive to 5-fluorouracil, amphotericin B and echinocandins in vitro, and the resistant rates of fluconazole, voriconazole and itraconazole were 44%, 47% and 60%, respectively.

Sixty four patients recovered, and 36 died. Seventy-eight patients with C. tropicalis BSI received empirical antifungal therapy: azoles (42 cases), echinocandins (29 cases), azole+echinocandin (4 cases), polyene (2 cases), and echinocandin+polyene (1 case). Among them, isolates of 58 cases were sensitive to empirical antifungal drugs, and isolates of 20 cases were resistant. Statistical analysis showed that the case fatality rate of the empirically sensitive group was lower, as shown in Table 3.

Table 3.

Univariate analysis of risk factors of death in patients with C. tropicalis bloodstream infection.

Factors  Total  Deceased patientsn=36 (%)  Non-deceased patientsn=64 (%)  p-Values 
Age    50.78±16.95  54.37±17.59  0.3215 
≥60 years  35  11 (30.6)  24 (37.5)  0.485 
Underlying disease
Hematological malignancy  40  16 (44.4)  24 (37.5)  0.496 
Solid organ tumor  16  5 (13.9)  11 (17.2)  0.666 
Diabetes  15  3 (8.3)  12 (18.8)  0.161 
Renal insufficiency  23  9 (25.0)  14 (21.9)  0.722 
Solid organ transplantation  18  7 (19.4)  11 (17.2)  0.778 
Lack of neutrophils  29  13 (36.1)  16 (25)  0.240 
Chronic obstructive pulmonary disease  36  23 (63.9)  13 (20.3)  <0.001 
Hypoproteinemia  33  18 (50)  15 (23.4)  0.007 
Related treatment
Deep vein catheterization  44  20 (55.6)  24 (37.5)  0.081 
Indwelling gastric tube  28  12 (33.3)  16 (25)  0.373 
Indwelling catheter ≥7 days  34  18 (50)  16 (25)  0.011 
Mechanical ventilation  30  16 (44.4)  14 (21.9)  0.018 
Parenteral nutrition ≥5 days  64  27 (75)  37 (57.8)  0.086 
Indwelling cavity drainage tube  26  6 (16.7)  20 (31.3)  0.111 
Use of broad-spectrum antibiotics ≥5 d  80  31 (86.1)  49 (76.6)  0.252 
Hemodialysis  15  7 (19.4)  8 (12.5)  0.351 
Recent exposure to azoles ≥2 weeks  32  16 (44.4)  16 (25)  0.045 
Long-term use of glucocorticoids and/or immunosuppressants  32  19 (52.8)  13 (20.3)  0.001 
Tumor chemotherapy  45  20 (55.6)  25(39.1)  0.112 
Empirically sensitive antifungal therapy  58  16 (44.4)  42 (65.6)  0.039 
Target sensitive antifungal therapy  76  20 (55.6)  56 (87.5)  <0.001 
Fluconazole resistant C. tropicalis  44  21 (58.3)  23 (35.9)  0.03 
Chronic obstructive pulmonary disease

Eighty five patients out of 100 received targeted antifungal therapy; 76 patients were treated with the appropriate antifungal (C. tropicalis was sensible to the treatment) sensitive drugs and 9 patients were not. The statistical analysis showed that using the appropriate antifungal in the target treatment led to a lower fatality rate (p<0.05), as shown in Table 3.

Patients were divided in two groups according to the outcome (death or survival). The univariate analysis showed poor prognosis (p<0.05) associated with the following factors: chronic obstructive pulmonary disease, hypoalbuminemia, indwelling catheter ≥7 days, mechanical ventilation, recent exposure to azoles ≥2 weeks, long-term use of glucocorticoids and/or immunosuppressants, and infection with fluconazole resistant-C. tropicalis strains (Table 3). Empirical usage of antifungal drugs in cases of C. tropicalis resistance led to poor outcome, whereas patients’ prognosis could improve in cases of sensible C. tropicalis strains. This suggest that the early use of the proper antifungal may could reduce the mortality of patients.

The Cox regression model analysis showed that hematological malignancies (OR=0.066, p=0.023), having an infection by a fluconazole resistant strain (OR=0.137, p=0.002), suffering chronic obstructive pulmonary disease (OR=0.205, p=0.002), or carrying an indwelling catheter (OR=0.136, p=0.007) were independent risk factor for death in patients with C. tropicalis BSI. Targeted treatment with a proper antifungal agent (OR=5.593, p=0.002) and the removal of drainage tubes (OR=8.782, p=0.012) were protective factors (Table 4).

Table 4.

Cox regression analysis of correlation factors for mortality of C. tropicalis bloodstream infection.

Factors  Regression coefficient  Standard error  Wald value  OR value (95% confidence interval)  p-Values 
Age (≥60 years)  0.146  0.542  0.073  1.158 (0.4, 3.352)  0.787 
Chronic obstructive pulmonary disease  −1.586  0.524  9.151  0.205 (0.073, 0.572)  0.002 
Hypoproteinemia  −0.521  0.431  1.464  0.594 (0.255, 1.381)  0.226 
Hematological malignancy  −2.713  1.193  5.173  0.066 (0.006, 0.687)  0.023 
Solid organ tumor  −1.308  0.75  3.038  0.27 (0.062, 1.177)  0.081 
Agranulocytosis  −0.896  0.843  1.129  0.408 (0.078, 2.131)  0.288 
Renal insufficiency  −1.502  0.801  3.514  0.223 (0.046, 1.071)  0.061 
Diabetes  1.45  0.75  3.735  4.265 (0.98, 18.563)  0.053 
Solid organ transplantation  0.761  0.592  1.652  2.141 (0.671, 6.834)  0.199 
Deep vein catheterization  −0.860  0.657  1.715  0.423 (0.117, 1.533)  0.19 
Indwelling catheter ≥7 days  −1.993  0.739  7.271  0.136 (0.032, 0.58)  0.007 
Indwelling gastric tube  0.983  0.703  1.958  2.673 (0.674, 10.599)  0.162 
Parenteral nutrition ≥5 days  −0.456  0.555  0.675  0.634 (0.213, 1.881)  0.411 
Indwelling cavity drainage tube  2.173  0.869  6.251  8.782 (1.599, 48.229)  0.012 
Mechanical ventilation  0.552  0.949  0.338  1.736 (0.27, 11.152)  0.561 
Tumor chemotherapy  1.242  0.796  2.434  3.462 (0.727, 16.479)  0.119 
Hemodialysis  −0.492  0.706  0.486  0.611 (0.153, 2.438)  0.486 
Recent exposure to azoles ≥2 weeks  0.329  0.487  0.456  1.389 (0.535, 3.605)  0.5 
Use of broad-spectrum antibiotics ≥5 days  1.06  0.634  2.798  2.888 (0.834, 10.004)  0.094 
Long-term use of glucocorticoids and/or immunosuppressants  −0.068  0.508  0.018  0.934 (0.345, 2.526)  0.893 
Empirically sensitive antifungal therapy  0.177  0.541  0.107  1.193 (0.414, 3.444)  0.744 
Target sensitive antifungal therapy  1.722  0.565  9.298  5.593 (1.850, 16.913)  0.002 
Fluconazole resistant C. tropicalis  −1.991  0.658  9.166  0.137 (0.038, 0.496)  0.002 
Discussion

In China, both the isolation rate of C. tropicalis and the resistance to fluconazole and voriconazole were significantly higher than the world average rates during the same period.14,32 In this group of C. tropicalis BSI cases, the proportion of hematological malignancies was the highest, which was consistent with the literature reports.20

The risk factors of fluconazole resistant C. tropicalis BSI have been rarely reported. Studies have shown that C. tropicalis is prone to infect patients with tumors or patients affected with neutropenia.9,10 It has been reported that C. tropicalis BSI is closely related to the formation of biofilms in urinary catheters.1 Our study shows that exposure to azoles within the preceding two weeks was an independent risk factor for death in fluconazole resistant C. tropicalis BSI. Studies have confirmed that exposure to azole antifungal drugs can lead to the increase of fluconazole resistant strains.5,7,28,33 Lortholary et al.19 found that the recovery of fluconazole resistant strains from the blood of patients recently exposed to azoles was significantly higher than that of caspofungin resistant strains, suggesting that fluconazole resistant strains were prone to cause BSI when exposed to azole antifungal drugs.

Our data show that the mortality of patients with C. tropicalis BSI was 36%, which is consistent with the literature.25 Several risk factors are associated with the prognosis of C. tropicalis BSI. These include multi-site Candida colonization, a high APACHE II score, and underlying conditions or complications such as malignant tumors, diabetes, hypoalbuminemia, sepsis, or septic shock. Additional factors involve the use of invasive devices-including central venous catheters and mechanical ventilation, as well as inappropriate antifungal.24 Our study shows that hematological malignancies are an independent risk factor for death in patients with C. tropicalis BSI. Indwelling catheterization is also an independent risk factor of high mortality, both in this study and the literature.31,35

Notably, the role of fluconazole-resistant C. tropicalis strains on prognosis had not been reported widely. This study shows that fluconazole resistant C. tropicalis strains was an independent risk factor for death in patients with C. tropicalis BSI. The data in this study also show that chronic obstructive pulmonary disease is an independent risk factor for death.

According to our results, using the proper antifungal drug improved the survival rate and played a key role in improving prognosis as well. Studies have shown17 that the high fatality rate of patients with fungal BSI has been related to both delayed or inadequate antifungal treatment. Therefore, early blood culture and targeted antifungal therapy are important to improve the prognosis. This study shows that resistance to echinocandins and amphotericin B in C. tropicalis is really low, suggesting that echinocandins and amphotericin B are still effective antifungal drugs to treat C. tropicalis BSI. It has been recommended that echinocandins should be used in critically ill patients with unstable conditions, especially in cases of BSI due to a fluconazole resistant Candida strain and previously treated with an azole antifungal.21 Amphotericin B was also preferred in patients with Candida BSI and neutropenia.21 In the case of empirical use of fluconazole, the in vitro susceptibility test is important. The data in this study also show that the removal of drainage tubes favoured the survival of patients.

In conclusion, we found that the exposure of azole antifungal agents was an independent risk factor for fluconazole resistant C. tropicalis BSI. Hematological malignancies, the infection with fluconazole-resistant strains, chronic obstructive pulmonary disease and portraying indwelling catheters were independent risk factors for death in patients with C. tropicalis BSI. An effective antifungal therapy was key to improve the prognosis and the removal of drainage tubes was a protective factor for the patients. Since this study was a single-center retrospective study and the sample size was relatively small, this conclusions needs to be further studied.

Funding

Foundation of Zhejiang Province Traditional Chinese Medicine Science and Technology Project. Grant/Award Number: 2021ZB010.

Conflict of interest

The authors declare that they have no competing interests.

Acknowledgment

This study was supported in part by a grant from the Foundation of Zhejiang Province Traditional Chinese Medicine Science and Technology Project.(Grant/Award Number: 2021ZB010).

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