Epidemiology, antifungal susceptibility, risk factors, and mortality of persistent candidemia in adult patients in China: a 6-year multicenter retrospective study | BMC Infectious Diseases

This was a 6-year retrospective multicenter study of PC and non-PC at three tertiary university hospitals in southwestern China. We analyzed clinical features, including demographics, underlying comorbidities, risk factors, distribution of candid species, antifungal therapy, antifungal agent susceptibility results, admitting department and patient outcomes, as well as patients with CP and without CP compared epidemiologically.

Table 4 Protective factor and predictors of PC and 30-day mortality in other studies from 2012-2021

Our data did not show significant differences in age, department of admission and 30-day mortality between patients with PC and without PC (P > 0.05). Our data were consistent with the findings of other studies conducted in adult patients with PC and without PC. [11, 18]. The incidence rate in adult patients with PC (0.03/1000 admissions) was significantly lower than in child 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 CP and non-PC, with the exception of 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 without 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 without 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 was higher in patients with CP than in patients without CP (P <0.05). After candid was identified in blood, VRC and FCA were used as first-line drugs against candid infection, which may be related to the high sensitivity of candid species to azole antifungal drugs (Table 2). Meanwhile, 21.1% (46/218) of patients were treated with the combination drug for Candida spp ., possibly due to drug resistance of candid or the severity of the patient’s condition. Although echinococcus is the first-line treatment for candidemia, caspofungin was the most widely used echinocandin drug in many countries. [21, 22]However, caspofungin also had a higher risk of inducing FKS mutations compared to other echinocandins. [21, 23], leading to a gradual increase in the rate of caspofungin resistance. There is no susceptibility testing for echinococcus in our region, which may be why clinicians were less likely to choose echinococcus as a first-line agent.

Our data showed that the number of female patients with PC was greater than that without PC, which was different from the results of other studies. However, the proportion of men was similar to that of other studies. [4, 11, 18]However, the proportion of women was similar to the result of the study of babies in China. [19]. Furthermore, the present study showed that the length of hospital stay was longer for patients with PC than for those without PC (P = 0.016), which was consistent with reports from other studies [4]. Patients with PC were mostly hospitalized in operating rooms, and non-PC mostly in medical rooms, similar to other studies that report hospitalization in Spain. [18]and different from those of Finland [4]. This phenomenon may be related to the demographic characteristics of patients admitted to different hospitals or regions. According to our study, C. albicans was the most common cause of candidemia in the entire region, but the proportion of non-C. albicans infections was higher than that of C. albicans infections in patients with PC. Furthermore, the proportion of C. parapsilosis in surgical, medical and ICU rooms was the highest for patients with PC, unlike 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 to few statistical samples (36 PC cases).

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 diagnostic and treatment characteristics of the hospitals and the basic conditions of the patients. In addition, 36 patients (13.7%) met the definition of PC, higher than that reported by Kang et al. [11]and lower than that reported by Ala-Houhala et al. [4]. The 30-day mortality in this study was similar to that of some hospitals in other countries. [4]but lower than in some other hospitals in other countries [11]. The reason may be that the most persistent candid Infections are caused by C. parapsilosis in this region, and are sensitive to all antifungal agents (Table 2), which may also be one of the reasons for the low mortality rate of persistent candid infection in this area. The 30-day mortality in ICU wards was the highest between patients with PC and without PC, which may be related to the severity of the underlying diseases in ICU patients and was consistent with other studies.

Resistance to FCA, ITR and VRC was common in C. albicans and not c. albicans species (Table 2). In our study, AMB and 5-FC were highly active against all candid species. In CP patients, the ITR resistance rate was the highest, and the ITR and FCA resistance rates were higher than those in non-CP patients. However, the resistance rate of candid species was not significantly different between patients with CP and without CP (P > 0.05), the resistance rate of candid species was not associated with the development of persistent candidemia, which is inconsistent with the result of another study [10]. Furthermore, FCA was very active against all candid species in patients with CP and without CP and could be used in patients with candidemia as a first-line agent. Throughout the region, the rate of resistance to azole was similar to those reported in other regions and countries. [25,26,27]but C. tropicalis and C. albicansshowed high resistance to azole antifungals in patients with PC from this region. The mechanism of drug resistance will be investigated in further studies. This may be related to the long-term use of azole antifungal drugs in patients with candidinfection. Therefore, the antifungal susceptibility of isolates from patients with candidthe infection should be tested to guide clinicians to choose antifungal drugs reasonably and avoid the continued increase in drug resistance.

In this study, we analyzed the risk factors in adult patients with PC and without PC using multifactorial regression, and the results revealed that the use of broad-spectrum antibiotics (OR: 5,925) and FCA (OR: 3,389), and C. parapsilosisinfection (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 shown that CVC( OR:2.71), foci of metastatic infection (OR:3.60), ineffective empirical treatment (OR:3.31) and unsuspected infection sites (OR:4.28) were independent risk factors for patients with PC [4, 11, 18]. 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 operating rooms were the common predictors of mortality in the univariate analysis (P< 0.05) in patients without PC, and the univariate predictors of poor outcome in patients with PC were lower than those of patients without PC (1 vs. 13 predictors), as shown in Table 3. C. tropicalisbloodstream infection was the only common predictor of mortality in univariate analysis (P< 0.05) in patients with PC; while it was also the only independent risk factor for 30-day mortality (OR: 12,642). The reason may be because C. tropicalishas a high resistance to azole antifungal drugs, leading to treatment failure in patients with C. tropicalisinfection, ultimately 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 an independent predictor of 30-day mortality in this study, however, some other studies reported corticosteroids in the past 30 days (OR: 5.31) and septic shock (OR: 5.81) were independent predictors of 30 -daily mortality. The length of hospital stay (OR: 0.925) and other invasive catheters (OR: 0.104) were the protective factors for 30-day mortality in patients without 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 demographics, underlying diseases, and risk factors risk of patients in our study were different. from those of other studies. This may be the reason 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. Firstly candidAntifungal susceptibility of isolates was tested using the ATB FUNGUS 3 kit (bioMérieux, France) in all three hospitals, the kit did not contain echinococcines, we only had data on the use of echinococcines, but no data on drug susceptibility . Second, although we performed a multicenter retrospective study, our total sample size was even smaller. Our data may be affected by insufficient sample size. Therefore, the results may not be generalizable to patients with persistent candidaemia in other regions of China.