Appropriate Therapy and Survival in Carbapenem-Resistant Enterobacterales Bacteremia: A Multicenter Cohort Study on Epidemiology and Risk Factors.

BACKGROUND

Carbapenem-resistant Enterobacterales (CRE) bloodstream infections are associated with high mortality and limited treatment options. This study aimed to characterize CRE epidemiology, identify risk factors for 30-day mortality, and evaluate the impact of appropriate combination therapy on mortality in patients with CRE bacteremia using treatment regimens prior to the adoption of novel β-lactam/β-lactamase inhibitors.

METHODS

This multicenter retrospective cohort study was conducted across 13 teaching hospitals in Korea. All notified CRE-positive cases (n=8,687) were analyzed descriptively, while all clinical outcome analyses were confined to patients with monomicrobial CRE bacteremia (n=358). Antibiotic appropriateness was independently evaluated by infectious disease specialists, and inverse probability of treatment weighting (IPTW) was applied to adjust for confounding between treatment groups.

RESULTS

Blood-positive specimens accounted for 12.4% of all CRE-positive cases, a proportion that has increased over time. Among the bacteremia cohort, the 30-day mortality was 34.1%. Independent predictors of 30-day mortality included higher qSOFA score (Odds Ratio [OR]=1.57; 95% Confidence Interval [CI] 1.22-2.01; P<0.001) and septic shock (OR=5.17; 95% CI 3.03-8.81; P<0.001). Combination therapy showed no overall survival advantage after IPTW adjustment. However, a significant mortality benefit was observed with definitive colistin-based combination therapy (adjusted OR=0.42; 95% CI 0.18-0.98; P=0.044) and in those with a high comorbidity burden (CCI ≥6; adjusted OR=0.34; 95% CI 0.12-0.98; P=0.046), though not in KPC-producing K. pneumoniae subgroup. Among KPC-producing K. pneumoniae isolates, amikacin and colistin retained high in vitro activity.

CONCLUSIONS

In CRE bacteremia, combination therapy did not confer a uniform survival advantage, but was associated with lower mortality in patients receiving colistin-based regimens and those with high comorbidity burden. Sustained antimicrobial stewardship and continuous susceptibility surveillance of blood isolates remain essential for optimizing patient outcomes in settings where novel agents are limited.