Emerging Waves of Carbapenem Resistance among Gram-negative Pathogens at a Tertiary Center

Background: The emergence of carbapenem-resistant Enterobacteriaceae (CRE), Acinetobacter (Ab), and Pseudomonas (Ps) have created a healthcare crisis. The purpose of this study was to evaluate the epidemiology and factors associated with CR at our center.

Methods: Microbiology records were extracted from 2000-2015 for common Gram-negative rods (GNRs): E. coli (Ec), Klebsiella pneumoniae (Kp), Ps, Enterobacter (En), Serratia (Sm) and Ab. 2016 CLSI breakpoints were applied to define CR.

Results: 85,619 isolates from 52,054 unique pts were identified. Ec was most common (34%), followed by Ps (27%), Kp (19%), En (11%), Sm (5%) and Ab (4%). Ec and Kp isolates rose over the study period (P=0.001 and 0.006, respectively); all other GNRs remained stable. 8,910 (10%) isolates from 5,162 (10%) pts were CR. 56% of pts were men, mean age (std dev) was 57.8 (15.9) years, and 18% were transplant recipients. 40% of pts resided in the ICU. 56% of isolates were from the respiratory tract, 18% urine, 16% wound, and 10% blood. Standardized by pt, overall CR rates increased from 4% in 2000 to 9% in 2016 (P<0.0001, R²=0.90); the incidence rose from 0.85 to 2.25 CR isolates/1000 pt days (P<0.0001). 55% of CR isolates were Ps, followed by Kp (15%), Ab (12%), En (10%), Ec (6%), and Sm (3%). Ps accounted for 87% of CR in 2000, but only 48% in 2016 (P<0.0001). On the other hand, CR Ab, Kp, and En increased from 4%, 1%, and 1% of CR isolates to 9%, 19%, and 15%, respectively (P<0.0001 for each). Rates increased dramatically for Ab (4 to 72%; P<0.0001), Kp (1 to 13%; P=0.0002), and En (1 to 14%; P=0.001). By time-series linear regression, rates of CR increased for all 6 GNRs (P<0.05). Ps was the most common CR pathogen each year; however, other CR GNR emerged in waves as second most common over time (CR Ab (2010), CR Kp (2012), and CR En (2014)). Carbapenem daily defined doses (DDDs) increased from 4.96 to 46.1 DDD/1000 pt days (P<0.001) and correlated with CR overall (P<0.001; R²=0.93). Among pts with CR En, CR Ps, CR Kp, CR Ab, or CR Ec bacteremia, 30d mortality rates were 22% (11/51), 32% (21/65), 37% (44/119), 50% (21/42), and 73% (8/11), respectively.

Conclusion: CR has emerged in waves at our center, and cause disproportionately high rates of death. Increasing rates of CR were driven by dramatic increases in CR Ab, Kp, and En in sequential 2 year periods. Previously susceptible organisms like CR Ec also emerged over the study period, and even at low rates of CR, may impact large numbers of pts.