Demographics and clinical characteristics
The median age was 68 years (IQR, 59-75), and 58.1% (68/117) of patients were male. The mono-CA-BSI and mixed-CA/B-BSIs were responsible for 93/117(79.5%) and 24/117(20.5%) cases, respectively. The most ward of CA-BSI occurrence was ICU (66.7%), followed by surgical ward (23.9%) and medical ward (9.4%). The solid tumor was the most common co-morbidity (28.2%), followed by diabetes mellitus (23.9%). There were no significant differences in age, gender, immune-suppression conditions, or ill severity between the two groups. Among surgical patients and ICU patients, 65.8% (77/117) and 66.7% (78/117) episodes were documented, respectively. Other common predisposing factors for candidemia included central venous catheter insertion (85/117, 72.6%), urethral catheter insertion (106/117, 90.6%), prior antibiotics exposure (93/117, 79.5%) and total parenteral nutrition (TPN) (85/117, 72.6%). Comparison with mono-CA-BSI, patients with mixed-CA/B-BSIs displayed longer ICU stay before candidemia onset [12.0(8.0,17.8) vs. 1.0(0.0,11.0), P =0.001], longer hospital stay before candidemia onset [19.0(12.0,30.8) vs. 12.0(2.0,26.5), P =0.031], longer duration of ventilation before candidemia onset [11.0(0.3,24.5) vs. 1.0(0.0,10.0), P =0.013], longer prior antibiotic exposure before candidemia onset [17.0(10.3,28.8) vs. 8.0(1.0,20.5), P =0.007], more need of life-sustaining treatments such as invasive mechanical ventilation (81.8% vs. 54.7%, P =0.020) and continuous renal replacement therapy (CRRT) (41.7% vs. 21.5%, P =0.044). Nonetheless, there were no statistical differences in proportions of surgical patients, blood transfusion, total parenteral nutrition, hypoproteinemia. The source of total CA-BSI was mainly from the intra-abdominal (25.6%, 30/117), followed by lower respiratory tract infection (25.6%, 30/117) and. CVC-related infection (11.1%,13/117). In comparison with mono-CA-BSI, the source of Candida in mixed-CA/B-BSIs didn't display a significant difference, as shown in Table 2.
A high percentage of delay in initiation empiric antifungal treatment (85.5%) was observed among all patients, whereas no difference was found between groups of mixed-CA/B-BSIs (75.0%) and mono-CA-BSI (88.2%). Besides, the total proportion of appropriate antifungal therapy was lower than 50% (36.8%), and it was similar in patients with mixed-CA/B-BSIs (33.3%) to that with mono-CA-BSI (37.6%), as shown in Table 2. The proportions of empiric treatment and appropriate antibiotic therapy for bacteremia in mixed-CA/B-BSIs is 33% (8/24) and 70% (17/24), respectively.
Antifungal susceptibility
The C. albicans in both groups exhibited 100% susceptibility to amphotericin B, walconazole, and voriconazole, while no resistance to fluconazole was observed. Notably, in the group of mono-CA-BSI and mixed-CA/B-BSIs, 11 (24.4%) and 2 (13.3%) cases were completely resistant to ketoconazole, respectively. There was no significant difference between the two groups in vitro antifungal susceptibility test, as shown in Table 3. Because the drug sensitivity kit used in our current microbiology laboratory does not contain echinocandin, the specific drug sensitivity of C.albicans to echinocandin was not clear.
Independent risk factors for mixed-CA/B-BSIs
Variables with P values of <0.05 including prior hospital stay>7days, prior ICU stay>2days, prior antibiotic exposure>7days,prior mechanical ventilation>2days,CRRT before candidemia onset were entered into the multivariable logistic regression model to identify factors associated with mixed-CA/B-BSIs. As shown in Table 4, the independent risk factor of mixed-CA/B-BSIs was prior ICU stay>2days (adjusted odds ratio [OR], 7.808; 95% confidence interval [CI], 1.264-48.233).
Species distribution of the concomitant bacterial isolated from the mixed-CA/B-BSIs
The most common co-pathogen was Gram-positive bacteria (52.0%), followed by Gram-negative bacteria (48.0%). In terms of the exact microorganisms, the most frequent pathogen was Coagulase-negative Staphylococcus (CNS) (24.0%), followed by Klebsiella pneumoniae (k.pneumoniae) (20.0%) and Staphylococcus aureus(S.aureus) (16.0%). The detailed distribution of concomitant bacterial species in mixed-CA/B-BSIs was shown in Figure 2.
Outcomes
The median length of ICU stay was 14 days (IQR, 1.0-33.0), and the median length of hospital stay was 33 days (IQR, 18.0-56.0). In comparison with mono-CA-BSI, patients with mixed-CA/B-BSIs developed prolonged length of ICU stay [8.0(0.0, 31.5) vs. 22.0(14.3, 42.2), P =0.010] and longer mechanical ventilation time [3.0(0.0, 24.5) vs. 17.5(4.5, 34.8), P =0.019]. The incidence of septic shock, 28-day or 60-day mortality rates, or in-hospital mortality in patients with mixed-CA/B-BSIs were not different from those with mono-CA-BSI (Table 5, Figure 3).