Mortality associated with third generation cephalosporin-resistance in Enterobacteriaceae infections: a multicenter cohort study in Southern China

Background: Emerging third-generation cephalosporin-resistant Enterobacteriaceae (3GCR-EB) pose global healthcare concern. This study assessed the in-hospital mortality attributed to 3GCR-EB. Methods: The study cohort comprised inpatients with community-onset or healthcare-associated infection caused by Enterobacteriaceae in three tertiary-care public hospitals in 2017. In-hospital mortality was compared between 3GCR-EB infected patients and third-generation cephalosporin-susceptible Enterobacteriaceae (3GCS-EB) infected patients using competing risk survival models. Results: Of 2,343 study patients (median age 60 years; 45.2% male), 1,481 (63.2%) had 3GCS-EB and 862 (36.8%) 3GCR-EB infection. 494 (57.0%) 3GCR-EB isolates were co-resistant to fluoroquinolones and 15 (1.7%) to carbapenems. In-hospital mortality was similar in 3GCS-EB and 3GCR-EB infections (2.4% vs. 2.8%; p = 0.601). No increase in the hazard of in-hospital mortality was detected for 3GCR-EB compared to 3GCS-EB infection (sub-distribution hazard ratio [HR] 0.80; 95%CI, 0.41-1.55) adjusting for patient age, sex, intensive care admission, origin of infection and site of infection. Analysis of cause-specific hazards showed that 3GCR-EB infections significantly decreased the daily rate of hospital discharge (cause-specific HR = 0.84; 95%CI, 0.76-0.92) leading to lengthier hospitalizations. Conclusion: 3GCR-EB infection per se was not associated with increased in-hospital mortality in this study, but placed significant healthcare burden by increasing the length of hospitalization.