Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.

Risk factors and outcomes of patients colonized with carbapenemase-producing and non–carbapenemase-producing carbapenem-resistant Enterobacteriaceae

“…On univariate analysis, as in previous studies, [9][10][11]17,[21][22][23] we found that risk factors for both CP-CRE colonization and non-CP-CRE colonization included nursing home residency before hospital admission, antibiotic treatment 3 months before admission, urinary catheter, decubitus ulcer, and mechanical ventilation. We did not find men to be at an increased risk for CP-CRE or non-CP-CRE colonization in comparison to other studies, 9,10 which may have been due to an older patient population in our study and the longer life expectancy of women in Israel.…”

“…CRE resistance can be divided into 2 major groups: CP-CRE and non-CP-CRE. Previous studies [9][10][11][12][17][18][19][20][21][22][23][24] have addressed the issue of risk factors for CRE colonization/infection as a whole (ie, 1 group), showing that the following factors were associated with CRE acquisition: male sex, nursing home residency before hospital admission, history of admission within 1 year, poor functional status, Charlson index score ≥3, urinary catheter, decubitus ulcer, mechanical ventilation, intensive care unit stay, undergoing an invasive procedure with a scope device, and prior antibiotic exposure including penicillins, cephalosporins, carbapenems, vancomycin and fluoroquinolones.…”

“…common carbapenemase genes in the Unites States and in Israel are bla KPC ; however, other carbapenemase genes, including bla NDM , bla VIM , bla IMP , and bla OXA , have been increasingly observed. [9][10][11] These resistance patterns have important infection control implications. CP-CRE seems to be primarily responsible for the increasing spread of CRE in the United States and therefore has been targeted for aggressive prevention.…”

The Clinical and Molecular Epidemiology of Noncarbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae: A Case-Case-Control Matched Analysis

“…Even the 2015 guidelines by the Centers for Disease Control and Prevention do not differentiate between the 2 entities in terms of infection control-suggested measures (although it does acknowledge the issue) [ 10 ]. As depicted in this study and by others [ 15 , 16 , 20 , 21 ], the epidemiology of non-CP-CRE differ considerably from that of CPE, and therefore measures should be tailored based of controlled analyses.…”

“…In addition, clinical epidemiological analyses of this clinical and microbiological entity are lacking: however, although the mode of acquisition and the transmission dynamics of CPE clearly demonstrated “patient-to-patient” horizontal spread [ 9 , 15 ], the mode of acquisition for non-CP-CRE is still undetermined [ 15 ]. In a recent multicenter, retrospective, noncontrolled analysis from Singapore, recent carbapenem exposure was 3 times more common among patients with new acquisitions of non-CP-CRE compared with patients who acquired CPE [ 16 ]. Moreover, a small report suggested that non-CP-CRE new isolations are not commonly clustered in time nor space [ 17 ], and these 2 findings suggest that non-CP-CRE acquisition stems from endogenous emergence of carbapenem resistance among susceptible strains rather than “patient-to-patient transmission” [ 15 ], but controlled data are lacking.…”