Impact of Immunosuppressed Status on Prognosis of Carbapenem-Resistant Organisms Bloodstream Infections

Patient CharacteristicsCharacteristics of All Patients

A total of 334 episodes of 317 patients were screened, and finally 279 patients were included in the study, among whom 88 (31.5%) were immunocompetent and 191 (68.5%) were immunosuppressed (Fig. 1). Patients were mostly male (63.4%), with a median age of 61 (IQR 49–70) years. Hospital- and ICU-acquired infections accounted for 90.7% and 45.5%, respectively. Carbapenem-resistant Acinetobacter baumannii (CRAB) accounted for the highest proportion of 42.7%, followed by Carbapenem-resistant Enterobacterales (CRE) (36.9%). More than half of patients (57.0%) were admitted to ICU on the day of bacteremia, and 60.9% experienced septic shock. The proportions of appropriate empirical therapy and early appropriate therapy were 37.6% and 51.3%, respectively. Most patients (62.0%) received appropriate antimicrobial therapy (Table 1). Regrading the antibiotic susceptibility results of CRO species, 93.1% of all isolates were sensitive to polymyxin, and 68.2% of non-Pseudomonas aeruginosa species were sensitive to tigecycline. Except for CRAB, 80.4% of isolates were sensitive to ceftazidime avibactam (Supplementary Material 1).

Fig. 1figure 1

Flowchart of participants through this study. CRO Carbapenem-resistant organisms

Table 1 Comparison of clinical characteristics between survivors and non-survivors in 30 days with CRO bloodstream infections

In terms of outcomes, 3-day, 7-day and 30-day mortality were 30.8%, 40.9% and 58.8%, respectively. The median length of stay after CRO-BSI onset was 29 (IQR 16–49) days.

Characteristics Between Immunocompetent and Immunosuppressed Patients

Compared with the immunocompetent patients, the immunosuppressed patients had higher CCI scores (6 vs. 4, P = 0.001) and higher proportions of ICU-acquired infections (49.2% vs. 37.5%, P = 0.090). There was no significant difference in types of bacteria, source of BSI or severity of disease between the two groups. As for laboratory results, patients in the immunosuppressed group had lower lymphocyte (0.35 vs. 0.54 × 109/l, P < 0.001) and platelet (65 vs. 120 × 109/l, P < 0.001) values compared with the immunocompetent group.

There was no significant difference in 7-day mortality (33.0% vs. 44.5%, P = 0.091) and length of stay (30 vs. 29 days, P = 0.524) between immunocompetent and immunosuppressed populations, but the 30-day mortality rate was significantly higher in the immunosuppressed group (46.6% vs. 64.4%, P = 0.007). According to the bacterial species, the 30-day mortality rate of CRAB BSI was the highest, reaching 70.6% (84/119), which was significantly higher in the immunosuppressed group (79.1% vs. 48.5%, P = 0.001). The proportion of patients receiving appropriate therapy was similar between the two groups (61.4% vs. 62.3%, P = 0.986). There was no significant difference in 30-day mortality between the immunosuppressed group and immunocompetent group in patients receiving either monotherapy (52.1% vs. 38.2%, P = 0.183) or combination therapy (54.3% vs. 30.0%, P = 0.069).

Immunosuppression Was Not an Independent Risk Factor for 30-Day MortalityUnivariate Analysis and Multivariate Logistic Regression Analysis

A comparison of the survival and non-survival group is shown in Table 1. The proportion of immunosuppressed population in the non-survival group was 75.0% (123/164), while it was only 59.1% (68/115) in the survival group (P = 0.007). The proportion of ICU-acquired infections in the non-survival group was statistically higher (55.5% vs. 31.3%, P < 0.001). For laboratory results, patients in the non-survival group had a higher proportion of lymphopenia (62.8% vs. 46.1%, P = 0.008) and thrombocytopenia (72.6% vs. 40.0%, P < 0.001) compared with the survival group. There was no significant difference in the proportion of appropriate empirical therapy between the survival and non-survival group, but the proportion of early appropriate therapy and appropriate therapy in the non-survival group was significantly lower.

There was no significant difference in 30-day mortality between monotherapy and combination therapy among patients receiving appropriate therapy (47.7% vs. 47.0%, P = 0.929). Active antibiotic treatments for patients with appropriate antimicrobial therapy are shown in Table 2.

Table 2 Active antibiotic treatments for patients with appropriate antimicrobial therapya

Multivariable logistic regression showed that the independent risk factors for 30-day mortality of CRO-BSI included CCI (OR 1.23, 95% CI 1.06–1.44), ICU-acquired infection (OR 2.59, 95% CI 1.12–6.13) and thrombocytopenia (OR 4.09, 95% CI 1.85–9.34), while appropriate therapy (OR 0.27, 95% CI 0.12–0.62) was associated with decreased mortality (Table 3). Immunosuppression was not an independent risk factor associated with 30-day mortality of CRO-BSI (OR 1.14, 95% CI 0.48–2.66).

Table 3 Multivariate logistic regression analysis for risk factors of 30-day mortality in patients with CRO bloodstream infectionsSensitivity Analysis

We conducted two additional sensitivity analyses to explore the impact of immunosuppression on the mortality of CRO-BSI and obtained consistent results. Immunosuppression was not an independent risk factor for 30-day mortality in either sensitivity analysis: one excluding patients with solid tumors featuring the lowest mortality rate (OR 2.21, 95% CI 0.84–5.91; P 0.109) and the other considering only patients with hematologic malignancies as the immunosuppressed population (OR 3.53, 95% CI 0.74–18.89; P 0.123).

Propensity Score Matching and Inverse Probability of Treatment Weighting

The PSM resulted in 58 immunosuppressed patients matched to 58 immunocompetent patients. More participants were immunosuppressed; thus, 133 immunosuppressed patients were unmatched in contrast to 30 immunocompetent patients. Then, IPTW assessed from patients with all covariate data was included in the propensity analysis (n = 279). The results showed that immunosuppression was not an independent risk factor associated with 30-day mortality in CRO-BSI in either the PSM cohort (OR 1.38, 95% CI 0.60–3.18; P 0.449) or IPTW cohort (OR 1.40, 95% CI 0.58–3.36; P 0.447).

Risk Factors for 30-Day Mortality in Immunosuppressed Patients

In immunosuppressed patients, the 30-day mortality was 64.4% (123/164). The CCI (6 vs. 5, P < 0.001) and Pitt bacteremia score (4 vs. 1, P < 0.001) were statistically higher, and the blood culture time to positivity was significantly lower in the non-survival group (12 vs. 13.5 h, P = 0.009). More patients in the survival group received appropriate therapy (82.4% vs. 51.2%, P < 0.001) (Supplementary Material 2).

Results of multivariable logistic regression analysis showed that the independent risk factors for mortality in CRO-BSI included CCI (OR 1.45, 95% CI 1.16–1.88), glucocorticoid use (OR 15.78, 95% CI 2.32–152.12), ICU-acquired infection (OR 7.15, 95% CI 1.96–31.15), thrombocytopenia (OR 4.33, 95% CI 1.18–17.32) and Pitt bacteremia score (OR 1.51, 95% CI 1.16–2.09), while appropriate therapy (OR 0.10, 95% CI 0.02–0.42) was associated with decreased mortality (Table 4).

Table 4 Multivariate logistic regression analysis for risk factors of 30-day mortality in immunosuppressed patients with CRO bloodstream infections

No specific type of immunosuppression was an independent risk factor for 30-day mortality among immunosuppressed patients.

Among patients receiving appropriate antimicrobial treatment, 30-day mortality between monotherapy and combination therapy did not show a significant difference (52.1% vs. 54.3%, P = 0.807).

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