252 hospitalized pediatric patients were diagnosed with laboratory-confirmed BSI Between 2016 and 2018 at the West China Second Hospital, Sichuan University. Twenty-four patients were not included according to the exclusion criteria (Fig 1); Ultimately, we identified 228 patients in this study. 174 of the 228 patients(76.0%) had ESKAPEEc BSI. 6 of the 174 (3%) patients lacked resistance data; 124 (74%) were MDR ESKAPEEc and 44 (26%) were non-MDR ESKAPEEc.
Microbiology
As Table 1 showed, the two leading ESKAPEEc pathogens were Escherichia coli (26.8%,61/228), Klebsiella pneumoniae (20.2%,46/228), followed by Enterococcus faecium (12.7%, 29/228), Staphylococcus aureus (12.7%, 29/228), Acinetobacter baumannii (2.6%, 6/228), Pseudomonas aeruginosa (1.3%, 3/228) and Enterobacter spp (0). Of the 124 MDR ESKAPEEc strains, Escherichia coli and Klebsiella pneumoniae accounted for nearly 65.3%. 42 (33.9%) were ESBL-producing bacteria, including Escherichia coli (28,22.6%) and Klebsiella pneumoniae (14,11.3%). 20 (16.1%) were carbapenem non-susceptibility bacteria, including Klebsiella pneumoniae (15,12.1%), Escherichia coli (3,2.4%) and Acinetobacter baumannii (2,1.6%). In addition, there were 1 vancomycin-resistant Enterococcus faecium and 8 methicillin-resistant Staphylococcus aureus.
Comparison of ESKAPEEc and non-ESKAPEEc BSI
The main characteristics of patients with ESKAPEEc and non-ESKAPEEc BSI were summarized in Table 2. Less than half of the patients were males (42.1%, 96/228) and the median age was 4.4 (range:0.7-35.7) months. The median age between the two groups (median month, 2.5 [0.5-12.3] vs 32.7[8.0-100.4], P<0.001) showed statistically significant difference. Regarding underlying disease, a greater proportion of premature and/or low birth weight (31.6% vs 9.3%, P=0.001), tumor diseases (16.7% vs 0%, P < 0.001) was presented in patients with ESKAPEEc BSI. Compared with non-ESKAPEEc BSI, patients with BSI caused by ESKAPEEc had increased percentages of previous surgery and/ or trauma(13.8% vs 3.7%, P=0.042), nosocomial infection (32.2% vs 7.5%, P<0.001), more source of urinary tract infection (14.9% vs 1.9%, P=0.009), but lower rate of previous antibiotic use (25.9% vs 50.0%, P=0.001), less source of lung infection(17.8% vs 42.6%, P<0.001), intracranial infection(1.1% vs 16.7%, P<0.001) and lower levels of platelet count (median, 209 [111-323] vs 341 [168-439], P<0.001) , C-reactive protein (median mg/dL,15.0 [3.0-85.3] vs 26.5 [10.0-116.6], p=0.017). After applying the multivariate analysis, premature and/or low birth weight (odds ratio [OR]=2.981, P=0.036), previous surgery and/or trauma (OR=5.71, P=0.029) and source of urinary tract infection (OR=10.6, P=0.004) were independent risk factors for ESKAPEEc BSI. Source of intracranial infection was a protective factor for ESKAPEEc BSI(OR=0.198, P=0.037).
In terms of empiric antimicrobial treatment and outcomes of all cases, we found that 50 of the 228 patients (21.9%) were treated inappropriately:46 (27.4%, 46/174) were in ESKAPEEc BSI patient group and 4 (7.5%,4/54) were in non-ESKAPEEc BSI group. Patients with ESKAPEEc BSI had received inappropriate empiric antibiotics treatment significantly more often (27.4% vs 7.5%, p=0.003)(Table 2). Although no significant differences in the MODS, septic shock, mechanical ventilation, PICU admission and mortality between ESKAPEEc and non-ESKAPEEc BSI groups were found (all p>0.05). Patients with BSI due to ESKAPEEc had longer hospital stay (median days, 20.5[10.0–31.0] vs 14.0[8.8–23.0], p=0.023) compared with those with non-ESKAPEEc BSI.
Comparison of MDR ESKAPEEc and non-MDR ESKAPEEc BSI
The 168 patients with resistance data were divided into MDR ESKAPEEc and non-MDR ESKAPEEc BSI groups. The differences of the main characteristics between the 2 groups were showed in Table 3. MDR ESKAPEEc patients with BSI had more nosocomial infections (41.1% vs 11.4%, P<0.001) and the presence of underlying disease (72.6% vs 43.2%, P < 0.001) was also higher, whereas the age and sex between the 2 groups were not statistically different. Compared with non-MDR ESKAPEEc BSI, patients with MDR-ESKAPEEc BSI were less likely to have a history of antibiotic use within 1 month (21.8% vs 43.2%, P= 0.006), source of skin or soft tissue infection (6.5% vs 27.3%, P<0.001). Furthermore, the median level of platelet count was significantly lower in MDR-ESKAPEEc group with BSI than that in non-MDR ESKAPEEc group (median,188[100-302] vs 271[173-413], P=0.004). In multivariate analysis, the independent risk factor for MRD-ESKAPEEc BSI was nosocomial infection (OR=3.314, P=0.037), while the skin or soft tissue infection (OR=0.245, P=0.011) was a protective predictor of MRD ESKAPEEc BSI.
Regarding empiric antimicrobial treatment and outcomes for MRD ESKAPEEc BSI, 42 of the 124 MDR-ESKAPEEc patients with BSI (33.9%) were treated inappropriately in comparison with the 4 of the 44 non-MDR ESKAPEEc patients with BSI (9.1%) (P=0.002) (Table 3). Hospital stay in MDR-ESKAPEEc BSI group was longer than that in non-MDR ESKAPEEc BSI group (median days, 24.0 [13.0-36.0] vs 14.5 [9.0-27.3], P=0.006) (Table 3).Whereas, no significant differences were ascertained in MODS, septic shock, mechanical ventilation, PICU admission, mortality between MDR and non-MDR ESKAPEEc BSI groups (all p>0.05).
Predictors for mortality among hospitalized children with ESKAPEEc BSI.
A total of 174 hospitalized children with ESKAPEEc BSI were identified in our study. The overall mortality rate of these patients was 14.0% (25/174 ), and no significant difference was ascertained regarding mortality between MRD-ESKAPEEc and non-MRD ESKAPEEc BSI groups (13.7% vs. 11.4%, P=0.692) (Table 3). In the univariate analysis (Table 4), previous surgery and/or trauma, previous antibiotic use, neutrophil percentage, hemoglobin, platelet count, MODS, blood products transfusion, mechanical ventilation, PICU admission were statistically differences between survivor and non-survivor groups (all p<0.05). A multivariate analysis demonstrated that previous surgery and/or trauma (OR=7.006, P=0.006), mechanical ventilation (OR=7.997, P= 0.004) appeared to be effective predictors for death. Previous antibiotic use (OR=0.132, P=0.034), normal platelet count(OR=0.996, P= 0.037) were protective factors for death caused by ESKAPEEc BSI.