A total of 769 adult patients received ECMO for cardiogenic shock or respiratory failure between January 2015 and May 2021. Of them, 289 patients were excluded from the analysis. A total of 480 patients were included in the final analysis, of whom 368 and 112 comprised the non-BSI and BSI groups, respectively. The total duration of ECMO use was 5604.8 ECMO-days, and the BSI incidence was 20.0 episodes per 1,000 ECMO-days. Approximately 20.2% (97/480) and 5.4% (26/480) of the patients developed bacteremia and candidemia, respectively; meanwhile, both bacteremia and candidemia occurred sequentially or simultaneously in 2.3% (11/480) of the patients (Figure 1).
Table 1 displays the baseline characteristics of patients in the non-BSI and BSI groups, while Table 2 shows a comparison of the non-BSI group and the bacteremia or candidemia group. As indicated in Table 1, the mean age of the participants was 56.3±14.5 years, and 65.4% of them were men. Patients in the BSI group were older than those in the non-BSI group (58.8 vs. 55.5, p=0.024). The BSI group had a lower proportion of patients with congestive heart failure (CHF) (42.9% vs. 53.5% vs. p=0.048); moreover, the candidemia group had a lower proportion of patients with CHF than in the non-BSI group (30.8% vs. 53.5% p=0.026). The number of patients requiring hemodialysis, including intermittent or continuous, was higher in the BSI group (59.8% vs. 41.1%, p=0.001), especially in the bacteremia group. The median length of pre-ECMO hospital stay was significantly longer in the bacteremia (23.0 days) and candidemia (25.5 days) groups than in the non-BSI group (13.0 days). Over 70% of the patients were already receiving antibiotics, and more than 60% were using antibiotics with Pseudomonas coverage. The rate of antibiotic use before ECMO did not differ between the non-BSI and BSI groups.
Association of BSI with the reason for ECMO and mode of ECMO
Of the 480 patients, 267 received ECMO for cardiogenic support, and 213 received ECMO for respiratory support. The BSI group had a higher proportion of patients who received ECMO for respiratory support (53.6% vs. 41.6%, p=0.027) compared with that of the non-BSI group, indicating that patients requiring ECMO for respiratory support had a higher risk of developing BSI (Tables 1 and 2). The VA, VV, and VAV ECMO modes were used in 244, 130, and 106 patients, respectively. The frequent reasons for receiving VA support were sudden cardiac arrest, acute myocardial infarction, acute decompensated heart failure, and refractory arrhythmia. For VV support, bridge-to-lung transplantation and acute respiratory distress syndrome were the most common clinical conditions that require ECMO. When the mode of ECMO support was compared, higher portion of patients in VAV mode developed BSI. The rate of BSI in VAV mode was 34.9% (37/106 cases), VA was 25.4% (33/130 cases), and VV was 17.2% (42/244 cases).
Duration of ECMO and risk of BSI
The total duration of ECMO support in median days was higher in the bacteremia and candidemia groups (13.0 and 17.2 days) compared with that in the non-BSI group (6.11 days) (p=0.003 and 0.001, respectively). The in-hospital mortality rate was also higher in the bacteremia and candidemia groups (57.7% and 69.2%, respectively) compared with that in the non-BSI group (43.6%) (P=0.013 and 0.012, respectively). The Kaplan-Meier curves in Figure 2a and b show that the mortality curve rapidly dropped in both the bacteremia and candidemia groups compared with that in the non-BSI group.
Figure 3 shows the number of BSI cases at different periods after ECMO cannulation. The number of BSI cases increased as ECMO cannulation time increased. Approximately 71.1% of patients developed BSI after more than 6 days of ECMO cannulation. The median onset time of BSI was 8.0 days (range: 5.0–16.0 8.0): 8.0 (5.0–13.5) for bacteremia and 11.0 (6.0–20.0) for candidemia, respectively. According to ECMO mode, the median numbers of days of BSI onset was 7.0 (6.0–20.0) in patients who used the VA mode, 9.0 days (2.5–20.0) in patients who used the VV mode, and 13.5 median days (8.75-22.5) in patients who used the VAV mode.
Risk factor associated with BSI in ECMO
The risk factors associated with bacteremia and candidemia during ECMO were analyzed using univariable and multivariable logistic regression analyses (Table 3). In univariable analysis, age, hemodialysis, respiratory support, VAV mode, ECMO system with PLS, cannulation procedure performed in the intervention room, pre-ECMO hospital days, and total duration of ECMO were the risk factors of bacteremia. In the multivariable analysis, only hemodialysis (OR=2.647, 95% CI=1.547–4.528, p<0.001), VAV mode (OR=1.911, 95% CI=1.065–3.429, p=0.030), and total duration of ECMO (OR=1.030, 95% CI=1.008–1.053, p=0.007) were the significant clinical factors associated with an increased risk of bacteremia. Moreover, only the total duration of ECMO (OR=1.035, 95% CI=1.008–1.061, p=0.010) was associated with the risk of candidemia.
Major causal pathogens of BSI during ECMO
Table 4 lists the frequently isolated causal pathogens of bacteremia or candidemia during ECMO along with the first isolated time of each organism (in median days). Among the gram-negative organisms, Acinetobacter baumannii and Klebsiella pneumoniae were the most commonly detected pathogens of BSI during ECMO. Both organisms displayed multidrug resistance to antibiotics. All isolated Escherichia coli was either extended-spectrum beta-lactamase-producing (5 out of 6) or multidrug-resistant organism (1 out of 6). Coagulase-negative staphylococcus (methicillin resistant) and enterococcus (vancomycin resistant) were common pathogens in gram-positive organisms. Candida tropicalis was the most common Candida species, followed by Candida parasilosis and Candida albicans.
Figure 4 shows the microorganisms isolated on the first median days, in chronological order, to visualize the pathogens responsible for developing BSI in the early or later phase of ECMO. Bacteremia due to Enterobacter cloacae and Escherichia coli occurs in the earlier phase (less than 7 days) after ECMO cannulation. By contrast, vancomycin-resistant enterococcus, Candida glabrata, Candida parasilosis, and Morganella morganii were causal pathogens of BSI during ECMO, which developed in the later phase (after 15 days) of ECMO cannulation.
Table 5 shows the cases in which the causal pathogens were isolated from other sources before causing BSI. Furthermore, the causative microorganisms in BSI 37 out of 98 (37.8%) patients in the bacteremia group and 9 out of 26 (34.6%) patients in the candidemia group were previously isolated from other sources, such as sputum, urine, bronchial alveolar lavage, pleural drainage catheter, swab culture, endotracheal tube, or stool. Approximately 25.5% and 23.1% of bacteremia and candidemia pathogens, respectively, were isolated after ECMO cannulation. The most commonly isolated sources were sputum and bronchial alveolar lavage for bacteremia and sputum and urine for candidemia.