Comparing mortality in patients with carbapenemase-producing carbapenem resistant Enterobacterales and non-carbapenemase-producing carbapenem resistant Enterobacterales bacteremia.

Carbapenem-resistant Enterobacterales (CRE) are classified as either carbapenemase-producing CRE (CP-CRE) or non-carbapenemase-producing CRE (non-CP-CRE) based on their mechanism of carbapenem resistance. Few studies have compared outcomes associated with each type of infection. We attempted to determine if either CRE subset is associated with increased mortality. We performed a retrospective observational study to collect demographic, clinical and outcomes data to compare patients with CP-CRE and non-CP-CRE bacteremia. Of 146 cases analyzed, 88/146 (60%) were CP-CRE and 58/146 (40%) were non-CP-CRE. Patients with CP-CRE bacteremia were less likely to receive active empiric or targeted antibiotic therapy. Non-CP-CRE bacteremia was associated with a 2.4 times higher hazard of death at 30 days after bacteremia onset compared to CP-CRE (HR, 2.4; 95% CI, 1.2, 4.6). Patients with non-CP-CRE bacteremia had a higher hazard of death at 30 days after bacteremia onset compared to those with CP-CRE bacteremia.

Hovan MR ，Narayanan N ，Cedarbaum V ，Bhowmick T ，Kirn TJ ... -  《-》

Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia.

Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative. We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia. Clinical data were collected on all patients. A comprehensive DNA microarray-based assay was performed on all isolates to identify β-lactamase-encoding genes. There were 83 unique episodes of monomicrobial CRE bacteremia during the study period: 37 (45%) CP-CRE and 46 (55%) non-CP-CRE. The majority of CP-CRE isolates were bla KPC (92%), followed by bla NDM (5%) and bla OXA-48-type (3%). CP-CRE isolates were more likely to have meropenem minimum inhibitory concentrations (MICs) ≥16 µg/mL, while non-CP-CRE isolates were more likely to have meropenem MICs ≤1 µg/mL (P value < .001). A total of 18 (22%) patients died within 14 days, including 12 (32%) in the CP-CRE group and 6 (13%) in the non-CP-CRE group. Adjusting for severity of illness on day 1 of bacteremia, underlying medical conditions, and differences in antibiotic treatment administered, the odds of dying within 14 days were more than 4 times greater for CP-CRE compared with non-CP-CRE bacteremic patients (adjusted odds ratio, 4.92; 95% confidence interval, 1.01-24.81). Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.

Tamma PD ，Goodman KE ，Harris AD ，Tekle T ，Roberts A ，Taiwo A ，Simner PJ ... -  《-》

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bacteremia.

The aims of this study were to identify whether the site of acquisition or the underlying carbapenem-resistant Enterobacteriaceae (CRE) resistance mechanism was associated with clinical outcomes, and to evaluate risk factors for 14-day mortality in patients with CRE bacteremia. A retrospective cohort study was conducted at a 2700-bed tertiary center. All adult patients with monomicrobial carbapenem-resistant Escherichia coli or Klebsiella pneumoniae bacteremia from 2011 to 2018 were included. All blood isolates collected were tested with a modified carbapenem inactivation method for phenotypic detection of carbapenemase. Of 133 patients with monomicrobial CRE bacteremia, 63 (47.4%) were infected with carbapenemase-producing CRE (CP-CRE), and 70 (52.6%) with non-CP-CRE. Patients with community-onset infection (COI) were more likely to present with biliary or urinary tract infections, less likely to have ineradicable or non-eradicated foci and to receive appropriate empirical therapy, and marginally more likely to have CP-CRE compared with those with hospital-acquired infection (HAI). However, 14-day mortality was significantly lower in COI than HAI (7% vs 29%, P = 0.01). Patients who died were more likely to have had a higher APACHE II score, ineradicable or non-eradicated foci, and a lower chance of having received appropriate antibiotic treatment. Multivariate analysis revealed that HAI, high APACHE II score, and inappropriate antibiotic treatment were independent risk factors for mortality. Carbapenemase production did not affect mortality. The results of this study indicate that timely, appropriate treatment is essential for managing CRE bacteremia, regardless of carbapenemase production, particularly in critically ill patients with hospital-acquired bacteremia.

Seo H ，Lee SC ，Chung H ，Ra SH ，Sung H ，Kim MN ，Jung J ，Kim MJ ，Kim SH ，Lee SO ，Choi SH ，Kim YS ，Woo JH ，Chong YP ... -  《-》

Clinical and molecular characteristics and risk factors for patients acquiring carbapenemase-producing and non-carbapenemase-producing carbapenem-nonsusceptible-Enterobacterales bacteremia.

Carbapenem-nonsusceptible Enterobacterales (CNSE) are a growing global threat. Carbapenemases are often produced by plasmids, which allow rapid transmission. This study aimed to investigate (1) the bacterial type (2) resistant genes (3) antimicrobial susceptibility and (4) risk factors for acquisition of carbapenemase-producing carbapenem-nonsusceptible Enterobacterales (CP-CNSE) and non-carbapenemase-producing carbapenem-nonsusceptible Enterobacterales (non-CP-CNSE) bacteremia. There were a total of 113 isolates of Enterobacterales from 2013 to 2018. After excluding nonblood isolates and including only one sample from each patient, 99 isolates were analyzed and the medical charts of these patients were reviewed. Carbapenemase genes, β-lactamase genes and antimicrobial susceptibility of the isolates were determined. Multilocus sequence typing (MLST) was performed on CP-CNSE isolates. CP-CNSE carried more blaSHV (P = 0.004) and were more resistant to imipenem than non-CP-CNSE (P < 0.001). In the univariate analyses, we found that CP-CNSE bloodstream infection was associated with patient <65 years of age (odds ratio, 3.90; 95% confidence interval [CI], 1.16 to 13.10; P = 0.027), mechanical ventilation at the time of bloodstream infection (BSI) (odds ratio, 3.85; 95% CI, 1.16-12.78; P = 0.028) and exposure to piperacillin/tazobactam (odds ratio, 3.96; 95% CI, 1.09-14.38; P = 0.037). However, on multivariate analyses, no independent predictor for CP-CNSE was identified in this study. CP-CNSE carried more blaSHV and were more resistant to imipenem when compared to non-CP-CNSE. No independent predictor for CP-CNSE was identified after multivariate analysis. This is the first study conducted in Taiwan comparing risk factors between CP-CNSE and non-CP-CNSE from both clinical and molecular aspects.

Wu AY ，Chang H ，Wang NY ，Sun FJ ，Liu CP ... -  《-》

Role of Double-Carbapenem Regimen in the Treatment of Infections due to Carbapenemase Producing Carbapenem-Resistant Enterobacteriaceae: A Single-Center, Observational Study.

Cancelli F ，Oliva A ，De Angelis M ，Mascellino MT ，Mastroianni CM ，Vullo V ... -  《-》