Risk factors correlated with antibiotic-induced carbapenem resistant in Gram-negative bacilli in China: a retrospective cohort study

Abstract Background: Increasing resistance to carbapenem, particularly common in Gram-negative bacilli (GNB), has become a growing public health concern around the world. The objective of this study was to investigate risk factors associated with antibiotic-induced carbapenem resistant in Gram-negative bacilli (CR-GNB) among inpatients. Methods: A retrospective cohort study was conducted in one of the largest tertiary A-level hospitals including patients with GNB cultured from any of the clinical specimens who had been admitted for more than 2 calendar days from January 2017 to June 2019. Kaplan-Meier analysis and Cox proportional hazard model were used to estimate the hazard of CR-GNB induction by antibiotics. Results: 2490 patients including 7 cohorts were included. After cox proportional risk model analysis, carbapenems, β-lactamase inhibitors, and cephalosporins had significantly higher hazards than other types of antimicrobial (P<0.001). But even without using any antimicrobials, the hazard would increase with the length of hospital stay. On multivariate analysis, carbapenem was the most principal hazard factor for antibiotic-induced CR-GNB (hazard ratio [HR], 2.968; 95% confidence interval [CI], 1.706～5.162), followed by ICU admission (HR, 1.815; 95% CI, 1.507～2.186), cephalosporin (HR, 1.605; 95% CI, 1.288～1.999), tracheotomy (HR, 1.563; 95% CI, 1.251～1.952) and β-lactamase inhibitor (HR, 1.542; 95% CI, 1.237～1.921). However, quinolone effects on antibiotic-induced CR-GNB were not statistically significant. Conclusions: Prior carbapenem was a strong risk factor for antibiotic-induced CR-GNB, but quinolone was not associated with that. Rational use of carbapenems should be implemented and antimicrobial stewardship policies should be adjusted according to the characteristics of each hospital.