Patient characteristics
During the study period, a total of 570 cases of VAP caused by carbapenem-resistant gram-negative
bacteria were eligible for enrollment. A flow diagram showing the number of patients and reasons for exclusion is shown in Figure 1. Finally, 274 ICU-admitted patients with VAP caused by CRAB were included in the analysis. The baseline demographic characteristics and disease severities of the enrolled patients are presented in Table 1. Their mean age was 72.0 ± 14.8 years and 66.1% were men. More than one-third of them had a smoking history, and 64.2% were admitted to the medical ICU. Diabetes was the most common comorbidity (40.9%). The median APACHE II score on ICU admission was 23 (interquartile range [IQR] 17–28) and median SOFA score on the pneumonia index date was 7 (IQR 5–9), and 40.5% of the patients were using vasopressors when VAP was diagnosed. The median number of days on the ventilator before VAP occurrence was 8 (IQR 5–13), and the median number of days in the hospital before VAP occurrence was 10.5 (IQR 7–18).
Among the enrolled patients, 174 (63.5%) were under mechanical ventilation on day 21 after intubation and were categorized as ventilator-dependent patients. When compared with patients who were not ventilator dependent, patients with ventilator dependence were older (73.5 ± 14.2 years vs. 69.4 ± 15.6 years, P=0.037), had higher APACHE II score on ICU admission (24, IQR 19–28 vs. 21, IQR 15–25, P=0.002), had higher SOFA score on ICU admission (8, IQR 6–10 vs. 7, IQR 5–9, P=0.005), were more likely to use vasopressors (49.4% vs. 25.0%, P<0.001), have PF ratio <200 (36.2% vs. 22.0%, P=0.014), and undergo dialysis (30.5% vs. 17.0%, P=0.014). Moreover, before VAP, ventilator-dependent patients were on mechanical ventilation for a longer duration (10.0, IQR 6.0–14.0 vs. 6.0, IQR 4.0–8.0 days, P<0.001), had longer ICU stays (10.0, IQR 7.0–14.2 vs. 6.0, IQR 5.0–9.0 days, P<0.001), and longer hospital stays (12.0, IQR 8.0–19.0 vs. 8.0, IQR 5.0–15.0 days, P=0.001) than patients who were not ventilator dependent (Table 1)
Clinical outcomes of patients with and without ventilator dependence
We further compared the treatment outcomes of enrolled patients with and without ventilator dependence. As shown in Table 2, patients with ventilator dependence were under mechanical ventilation for longer time (41.0, IQR 29.0–58.2 vs. 12.0, IQR 9.0–17.0 days, P<0.001), spent longer time in the hospital (56.0, IQR 43.7–84.0 vs. 36.0, IQR 27.0–56.7 days, P<0.001) and ICU (28.5, IQR 21.0–43.0 vs. 16.0, IQR 12.0–21.0 days, P<0.001); they also exhibited higher all-cause mortality rate on day 28 (17.2% vs. 5.0%, P=0.003) and higher hospital mortality rate (38.5% vs. 12.0%, P<0.001). Kaplan–Meier analysis demonstrated that patients with ventilator dependence had significantly higher mortality rates than those without it (Figure 2). The curves separated early after day 21 of intubation.
Independent factor associated with ventilator dependence
Univariate and multivariate logistic regression analyses were performed to identify clinical factors associated with ventilator dependence in VAP patients. In univariate analysis as shown in Table 3, clinical factors associated with ventilator dependence included advanced age, higher APACHE II score on ICU admission, PF ratio <200, dialysis requirement, albumin ≤3 mg/dL, intravenous colistin administration, and late onset VAP. In multivariate analysis, independent clinical factors associated with ventilator dependence included advanced age (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00–1.04), higher APACHE II score on ICU admission (aOR, 1.04; 95% CI, 1.00–1.08; P=0.017), PF ratio <200 (aOR, 2.19; 95% CI, 1.20–3.99; P=0.010), and late onset VAP (6–10 days: aOR, 2.28, 95% CI, 1.04–4.99; P=0.039, >10 days: aOR, 3.92, 95% CI, 1.86–8.29; P<0.001).
Impact of VAP-onset times on ventilator dependence and treatment outcomes
To explore the impact of VAP-onset times on treatment outcomes, we categorized the patients into subgroups according to the hospital days before VAP occurrence (2–5 days, 6–10 days, >10 days). The demographic characteristics of patients with various VAP-onset times are shown in Supplementary Table 1.
As shown in Figure 3A, the day 21 ventilator-weaning rates in patients with VAP-onset times of 2–5 days, 6–10 days, and >10 days were 58.7%, 43.8%, and 28.8% respectively; the overall ventilator-weaning rate upon discharge was 73.9%, 73.0%, and 61.9% respectively. The day 21 ventilator-weaning rate was significantly higher in patients with shorter VAP-onset times. The day 28 mortality rates were 4.3%, 9.0%, and 18.0% in patients with ventilator-onset times of 2–5 days, 6–10 days, and >10 days, respectively, while the hospital- mortality rates were 23.9%, 19.1%, and 36.7% in patients with ventilator-onset times of 2–5 days, 6–10 days, and >10 days, respectively (Figure 3B). Patients with longer VAP-onset times had significantly higher mortality. The Kaplan–Meier analysis demonstrated that patients with longer VAP-onset times had significantly higher mortality rates (P=0.023) (Figure 4A). The curves separated early after day 21 of intubation. The Kaplan–Meier analysis also suggested that patients with longer VAP-onset times had significantly lower ventilator-weaning rates (P=0.013) (Figure 4B).