Changing Epidemiology and Decreased Mortality Associated With Carbapenem-resistant Gram-negative Bacteria, 2000-2017

Abstract

Background: Carbapenem-resistant gram-negative bacteria (CRGNB) continue to present a global healthcare crisis. We aimed to identify emerging trends of CRGNB over nearly 2 decades and describe the impact of CRGNB on patient outcomes.

Methods: Patients from whom CRGNB were isolated between 2000 and 2017 were included in the study. Carbapenem resistance was defined by the most recent breakpoints and applied across the study period. Patient demographics, clinical characteristics, and outcomes were retrieved from the electronic health record.

Results: A total of 94 888 isolates from 64 422 patients were identified; 9882 (10%) isolates from 4038 patients were carbapenem-resistant. Pseudomonas aeruginosa was the most common CRGNB each year. The second most common CRGNB emerged in waves over time. Carbapenem daily defined doses increased in parallel with CRGNB rates (R2 = 0.8131). The overall 30-day mortality rate was 19%, which decreased from 24% in 2000 to 17% in 2017 (P = .003; R2 = .4330). Among patients with CRGNB bloodstream infections (n = 319), overall 30- and 90-day mortality rates were 27% and 38%, respectively. Charlson score (adjusted odds ratio [aOR], 1.11 per point), intensive care unit residence (aOR, 7.32), and severe liver disease (aOR, 4.8.4) were independent predictors of 30-day mortality, while receipt of transplantation was associated with lower rates of death (aOR, 0.39). Among patients admitted between 2011 and 2017 (n = 2230), 17% died during hospitalization, 32% were transferred to long-term care facilities, and 38% were discharged home.

Conclusions: CRGNB emerged in waves over time, causing high rates of mortality. Despite increasing rates of CRGNB, overall patient outcomes have improved, suggesting that recognition and novel therapeutics have made a major impact.

Keywords: carbapenem resistance; epidemiology; mortality.

Figure 1.

Distribution of all gram-negative bacteria and carbapenem-related gram-negative bacteria, 2000–2017. A, All study organisms between 2000 and 2017 (n = 94 888). B, Total carbapenem-resistant gram-negative bacteria between 2000 and 2017 (n = 9882). Abbreviations: ACAT, Acinetobacter species; ECOL, Escherichia coli; E. coli, Escherichi coli; ENT, Enterobacter species; KLPN, Klebsiella pneumoniae; K. pneumonae, Klebsiella Pneumoniae; P. aeruginosa, Pseudomonas aeruginosa; PSAR, Pseudomonas aeruginosa; SERM, Serratia marcescensS. marcescens, Serratia marcescens; spp., species.

Figure 2.

A, Temporal changes in carbapenem resistance rates among unique patients with carbapenem-resistant gram-negative bacteria, 2000–2017 (n = 4038). B, Temporal changes in carbapenem resistance rates, 2000–2017. Abbreviations: ACAT, Acinetobacter species; ECOL, Escherichia coli; ENT, Enterobacter species; KLPN, Klebsiella pneumoniae; PSAR, Pseudomonas aeruginosa; SERM, Serratia marcescens.

Figure 3.

Temporal changes in carbapenem resistance rates among unique patients and antibiotic defined daily doses. Carbapenems: ertapenem, doripenem, imipenem, and meropenem. Cephalosporins: cefepime and ceftazidime. Fluoroquinolones: ciprofloxacin, levofloxacin, and moxifloxacin. Novel β-lactam/β-lactamase inhibitors: ceftazidime-avibactam and ceftolazane-tazobactam.

Figure 4.

Kaplan-Meier plots of 30-day survival of unique patients with carbapenem-resistant gram-negative bacteria (CRGNB), 2000–2017 (n = 4038), by organism (A), culture site (B), hospital location at time of carbapenem-resistant pathogen isolation (C), and lactose fermentation status of CRGNB (D). Abbreviations: ACAT, Acinetobacter species; ECOL, Escherichia coli; ENT, Enterobacter species; KLPN, Klebsiella pneumoniae; PSAR, Pseudomonas aeruginosa; SERM, Serratia marcescens.

Figure 5.

Rates of 30-day mortality over time for all carbapenem-resistant gram-negative bacteria, fermenters and nonfermenters, 2000–2017. Abbreviation: CRGNB, carbapenem-resistant gram-negative bacteria.