Epidemiology, antifungal susceptibility, risk factors, and mortality of ... - BMC Infectious Diseases
This was a 6-year multicenter retrospective study of PC and non-PC in three tertiary teaching hospitals in Southwest China. We analyzed the clinical characteristics, including the demographics, underlying comorbidities, risk factors, distribution of Candida species, antifungal therapy, antifungal agent susceptibility results, department of admission and patient outcomes, as well as epidemiologically compared patients with PC and non-PC.
Our data showed no significant difference in age, department of admission, and 30-day mortality between patients with PC and non-PC (P > 0.05). Our data were consistent with the findings of other studies conducted in adult patients with PC and non-PC [11, 18]. The incidence rate in adult patients with PC (0.03/1000 admissions) was significantly lower than in infant patients(5.5/1000 admissions) [19], This may be related to the clinical characteristics of the patients, and the infant's immune system is even worse [20]. Meanwhile, the proportion of underlying comorbidities in PC and non-PC, except for chronic/acute renal failure, was not significantly different (P > 0.05). The proportion of chronic/acute renal failure was lower in patients with PC than in those with non-PC (P < 0.05) (Fig. 2 and Supplementary Table S3). Among the risk factors, only CVC had higher risks in patients with PC than those with non-PC (P < 0.05), and the proportion of other risk factors was similar for both patients (P > 0.05) (Fig. 2 and Supplementary Table S3), consistent with previous studies [11, 18]. In therapy, the proportion of use of broad-spectrum antibiotics, FCA and capofungin + VRC were higher in patients with PC than in patients with non-PC (P < 0.05). After Candida was identified in blood, VRC and FCA were used as first-line drugs against the Candida infection, which may be related to the high sensitivity of Candida species to azole antifungal drugs (Table 2). Meanwhile, 21.1% (46/218) patients were treated with the combination drug for Candida spp., possibly because of the drug resistance of Candida or the severity of the patient's condition. Although echinococcus is the first-line therapy of candidemia, caspofungin was the most used echinocandin drug in many countries [21, 22], however, caspofungin was also a higher risk of inducing FKS mutations in comparison to other echinocandins [21, 23], leading to gradual increase in the resistance rate of caspofungin. There are no susceptibility tests for echinococcus in our region, which may be the reason why clinicians were less likely to choose echinococcus as an first-line agent.
Our data showed that the number of female patients with PC was higher than that with non-PC, which was different from the results of other studies. However, the proportion of men was similar to that in other studies [4, 11, 18], however, the proportion of female were similar to the result of infants study in China [19]. Moreover, the present study showed that the length of hospital stay was longer for patients with PC than for those with non-PC (P = 0.016), which was consistent with the reports of other studies [4]. The patients with PC were hospitalized mostly in surgical wards, and those with non-PC mostly in medical wards, which was similar to other studies that reported hospitalization in Spain [18], and different from those in Finland [4]. This phenomenon may be related to the demographic characteristics of the inpatients in different hospitals or regions. According to our study, C. albicans was the most common cause of candidemia in the whole region, but the proportion of non–C. albicans infections was higher than that of C. albicans infections in patients with PC. Moreover, the proportion of C. parapsilosis in surgical, medical and ICU wards was the highest for patients with PC, which was different from other studies in other countries [4, 11, 18]. This may be due to the demographic characteristics of the patients in different hospitals or regions, or few statistical samples (36 cases of PC).
Our data showed that the mean incidence of PC was 0.03 episodes/1000 admissions from 2016 to 2021. However, the incidence rate was different in different hospitals [4, 11, 18, 24], which was mainly related to the diagnosis and treatment characteristics of hospitals and the basic conditions of patients. Further, 36 patients (13.7%) fulfilled the definition of PC, which was higher than that reported by Kang et al. [11], and less than that reported by Ala-Houhala et al. [4]. The 30-day mortality in this study was similar to that in some hospitals in other countries [4], but lower than that in some other hospitals in other countries [11]. The reason may be that the most persistent Candida infections are caused by C. parapsilosis in this region, and they are sensitive to all antifungal agents (Table 2), which may also be one of the reasons for the low mortality rate of persistent Candida infection in this area. The 30-day mortality in ICU wards was the highest among patients with PC and non-PC, which may be related to the severity of underlying diseases in ICU patients, and was consistent with other studies.
Resistance to FCA, ITR and VRC was common in C. albicans and non-C. albicans species (Table 2). In our study, AMB and 5-FC were highly active against all Candida species. In patients with PC, the resistance rate of ITR was the highest, and the resistance rates of ITR and FCA were higher than those in patients with non-PC. However, the resistance rate of Candida species was not significantly different between patients with PC and non-PC (P > 0.05), the resistance rate of Candida species was not associated with the development of persistent candidemia, which is inconsistent with the result of another study [10]. Moreover, FCA was highly active against all Candida species in patients with PC and non-PC and could be used in patients with candidemia as a first-line agent. In the whole region, the resistance rate to azole was similar to those reported in other regions and countries [25,26,27], but C. tropicalis and C. albicans showed high resistance to azole antifungal drugs in patients with PC in this region. The mechanism of drug resistance will be researched in later studies. This may be related to the long-term use of azole antifungal drugs in patients with persistent Candida infection. Therefore, the antifungal susceptibility of the strains isolated from patients with persistent Candida infection needs to be analyzed so as to guide clinicians to choose antifungal drugs reasonably and avoid the continuous increase of drug resistance.
In this study, we analyzed the risk factors in adult patients with PC and non-PC using multifactorial regression, and the results revealed that use of broad-spectrum antibiotics(OR: 5.925) and FCA(OR: 3.389), and C. parapsilosis infection(OR: 6.143) were independent risk factors for patients with PC, and sex (male) (OR: 0.199) was the protective factor for PC, which was different from the results of other studies, the other studies have showed that CVC(OR:2.71), metastatic infection foci(OR:3.60), ineffective empirical treatment (OR: 3.31) and unsuspected sites of infection (OR: 4.28) were independent risk factors for patients with PC [4, 11, 18]. The age, length of hospital stay, respiratory dysfunction, cardiovascular disease, chronic/acute renal failure, other invasive catheters, mechanical ventilation, total parenteral nutrition, concomitant bacterial infections, septic shock, use of broad-spectrum antibiotics such as FCA and Capofungin + AMB, and surgical wards were the common predictors of mortality in the univariate analysis (P < 0.05) in patients with non-PC, and the univariate predictors of poor outcomes in patients with PC were less than those in patients with non-PC (1 vs. 13 predictors), as shown in Table 3. C. tropicalis bloodstream infection was only the common predictor of mortality in the univariate analysis (P < 0.05) in patients with PC; meanwhile, it was also the only independent risk factor for 30-day mortality (OR:12.642). The reason may be because C. tropicalis has a high resistance to the antifungal drugs of azole, leading to the failure of treatment in patients with C. tropicalis infection, finally, the death of patients, which was consistent with the findings of another study in South Korea (OR: 4.12) [11]. Respiratory dysfunction (OR: 5.763) was independent predictors of 30-day mortality in this study, however, some other studies have reported that corticosteroid within past 30 days (OR:5.31) and Septic shock (OR: 5.81) were independent predictors of 30-day mortality. The length of hospital stays (OR: 0.925) and other invasive catheters (OR: 0.104) were the protective factors for 30-day mortality in patients with non-PC. Previous studies have reported respiratory dysfunction(OR: 22.57) as an independent predictor [28]. However, the length of hospital stay (OR: 0.89) and other invasive catheters (OR: 0.04) reported here have rarely been reported in other studies, possibly because the demographic characteristics, underlying diseases and risk factors of the patients in our study were different from those in other studies. This may be why the independent predictors and protective factors in this study differed from those in other studies (see Table 4).
This study has two potential limitations. First, all Candida strain isolates were tested for antifungal susceptibility using ATB FUNGUS 3 kit (bioMérieux, France) in all three hospitals, the kit did not contain echinococcins, we only had data on the use of echinococcins, but no data on drug sensitivity. Second, although we conducted a multicenter retrospective study, our total sample size was still smaller. Our data may be affected by the insufficient sample size. Therefore, the results may not be generalizable to patients with persistent candidemia in other regions of China.
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