Demographics and clinical characteristics
The median age was 68 years (IQR, 59-75 years), and 58.1% (68/117) of the patients were male. Mono-CA-BSI and mixed-CA/B-BSIs were responsible for 93/117 (79.5%) and 24/117 (20.5%) cases, respectively. The most common ward associated with CA-BSI occurrence was the ICU (66.7%), followed by the surgical ward (23.9%) and medical ward (9.4%). Solid tumors were the most common comorbidity (28.2%), followed by diabetes mellitus (23.9%). There were no significant differences in age, sex, immune status, or illness severity between the two groups. In the 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 CVC insertion (106/117, 90.6%), urethral catheter insertion (106/117, 90.6%), prior antibiotic exposure (93/117, 79.5%) and total parenteral nutrition (TPN) (85/117, 72.6%). Compared with the mono-CA-BSI group, the mixed-CA/B-BSIs group had a longer ICU stay before candidemia onset [12.0 (8.0,17.8) vs. 1.0 (0.0,11.0) days, p=0.001], longer hospital stay before candidemia onset [19.0 (12.0,30.8) vs. 12.0 (2.0,26.5) days, p=0.031], longer duration of mechanical ventilation before candidemia onset [11.0 (0.3,24.5) vs. 1.0 (0.0,10.0) days, p=0.013], and longer prior antibiotic exposure before candidemia onset [17.0 (10.3,28.8) vs. 8.0 (1.0,20.5) days, p=0.007]; additionally, they were more likely to have an indwelling hemodialysis catheter [41.7% vs. 18.3%, p=0.015] and presence of two or more central venous catheters [50.0% vs. 25.8%, p=0.022], and they had higher rates 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 significant differences in the proportions of surgical patients, blood transfusion, TPN, or hypoproteinemia. The main source of CA-BSI was CVCs (29.1%, 34/117), followed by intra-abdominal catheters (20.5%, 24/117). The main sources of mixed-CA/B-BSIs were CVCs (29.2%, 7/24) and primary sources (29.2%, 7/24). The main source of mono-CA-BSI was CVCs (29.0%, 27/93), followed by intra-abdominal catheters (19.4%, 18/93). Compared with the sources of Candida in mono-CA-BSI, the sources of Candida in mixed-CA/B-BSIs were not significantly different, as shown in Table 2. Regarding infection source control, the rate of CVC removal within 48 h after the first positive sample in the mixed CA/B-BSI group was higher than that in the mono-CA-BSI group (54.2% vs. 29.0%, p=0.021), but there was no significant difference in the rate of fungal collection from drainage fluid between the two groups (20.8% vs. 15.1%, p=0.708) (see Table 2).
A high rate of delay of initiation of empiric antifungal treatment (85.5%) was observed among all patients, and no difference was found between the mixed-CA/B-BSIs (75.0%) and mono-CA-BSI (88.2%) groups. In addition, the total rate of appropriate antifungal therapy was less than 50% (36.8%), and it was similar between patients with mixed-CA/B-BSIs (33.3%) and those 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 patients were 33% (8/24) and 70% (17/24), respectively.
Antifungal susceptibility
The isolated C. albicans in both groups exhibited 100% susceptibility to amphotericin B, voriconazole, and no resistance to fluconazole was observed. Notably, in the mono-CA-BSI and mixed CA/B-BSIs groups, 11 (24.4%) and 2 (13.3%) cases were completely resistant to ketoconazole, respectively. There was no significant difference between the two groups in the in-vitro antifungal susceptibility test results, as shown in Table 3. Because the drug sensitivity kit used in our current microbiology laboratory does not include echinocandins, the specific drug sensitivity of C. albicans to echinocandins was unclear.
Independent risk factors for mixed-CA/B-BSIs
Variables with p-value of <0.05, including a prior hospital stay>7 days, a prior ICU stay>2 days, prior antibiotic exposure>7 days, prior mechanical ventilation>2 days, an indwelled hemodialysis catheter and the presence of two or more CVCs at the time of onset of candidemia, were entered into the multivariable logistic regression model to identify factors associated with mixed-CA/B-BSIs. As shown in Table 4, the only independent risk factor for mixed-CA/B-BSIs was a prior ICU stay >2 days (adjusted odds ratio [OR], 7.445; 95% confidence interval [CI], 1.152-48.132).
Species distributions of concomitant bacteria isolated from the mixed-CA/B-BSIs
The most common copathogens were gram-positive bacteria (52.0%), followed by gram-negative bacteria (48.0%). In terms of the exact microorganisms, the most frequent pathogen was 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 is 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). Compared with patients with mono-CA-BSI, patients with mixed -CA/B-BSIs had a prolonged length of ICU stay [8.0 (0.0, 31.5) vs. 22.0 (14.3, 42.2) days, p=0.010] and longer mechanical ventilation time [3.0 (0.0, 24.5) vs. 17.5 (4.5, 34.8) days, p=0.019]. The incidence of septic shock, 28-day and 60-day mortality, and in-hospital mortality in patients with mixed-CA/B-BSIs were not different from those in patients with mono-CA-BSI (Table 5, Figure 3).