We compared the activity of 8 novel β-lactam and tetracycline-derivative antibiotics against a cohort of clinical carbapenem-resistant Enterobacterales (CRE) isolates and investigated the incremental susceptibility benefit of the addition of an aminoglycoside, fluoroquinolone, or polymyxin to the β-lactam agents to assist with empiric antibiotic decision making.

A collection of consecutive CRE clinical isolates from unique patients at 3 US hospitals (2016–2021) was assembled. Broth microdilution was performed to obtain antimicrobial susceptibility testing results. Mechanisms of carbapenem resistance were investigated through short-read and long-read whole-genome sequencing.

Of the 603 CRE isolates, 276 (46%) were carbapenemase producing and 327 (54%) were non–carbapenemase producing, respectively. The organisms most frequently identified were Klebsiella pneumoniae (38%), Enterobacter cloacae complex (26%), and Escherichia coli (16%). We obtained the following percent susceptibility to novel β-lactam agents: ceftazidime-avibactam (95%), meropenem-vaborbactam (92%), imipenem-relebactam (84%), and cefiderocol (92%). Aminoglycosides and the polymyxins provided greater incremental coverage as second agents, compared to fluoroquinolones. Amikacin and plazomicin exhibited the greatest additive value. Ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol were active against 94% of the 220 KPC-producing isolates. Cefiderocol was active against 83% of the 29 NDM-producing isolates. Ceftazidime-avibactam had 100% activity against the 9 OXA-48-like–producing isolates. Tigecycline had the highest activity compared to other tetracyclines against KPC, NDM, or OXA-48-like–producing isolates.

Selection among novel agents requires a nuanced understanding of the molecular epidemiology of CRE. This work provides insights into the comparative activity of novel agents and the additive value of a second antibiotic for empiric antibiotic decision making.

Targeted screening for carbapenem-resistant organisms (CROs), including carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing organisms (CPOs), remains limited; recent data suggest that existing policies miss many carriers.

Our objective was to measure the prevalence of CRO and CPO perirectal colonization at hospital unit admission and to use machine learning methods to predict probability of CRO and/or CPO carriage.

We performed an observational cohort study of all patients admitted to the medical intensive care unit (MICU) or solid organ transplant (SOT) unit at The Johns Hopkins Hospital between July 1, 2016 and July 1, 2017. Admission perirectal swabs were screened for CROs and CPOs. More than 125 variables capturing preadmission clinical and demographic characteristics were collected from the electronic medical record (EMR) system. We developed models to predict colonization probabilities using decision tree learning.

Evaluating 2,878 admission swabs from 2,165 patients, we found that 7.5% and 1.3% of swabs were CRO and CPO positive, respectively. Organism and carbapenemase diversity among CPO isolates was high. Despite including many characteristics commonly associated with CRO/CPO carriage or infection, overall, decision tree models poorly predicted CRO and CPO colonization (C statistics, 0.57 and 0.58, respectively). In subgroup analyses, however, models did accurately identify patients with recent CRO-positive cultures who use proton-pump inhibitors as having a high likelihood of CRO colonization.

In this inpatient population, CRO carriage was infrequent but was higher than previously published estimates. Despite including many variables associated with CRO/CPO carriage, models poorly predicted colonization status, likely due to significant host and organism heterogeneity.

To determine the prevalence and acquisition of extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpCs (pAmpCs), and carbapenemases (“MDR Enterobacteriaceae”) colonizing children admitted to a pediatric intensive care unit (PICU).

Prospective study.

40-bed PICU.

Admission and weekly thereafter rectal surveillance swabs were collected on all pediatric patients during a 6-month study period. Routine phenotypic identification and antibiotic susceptibility testing were performed. Enterobacteriaceae displaying characteristic resistance profiles underwent further molecular characterization to identify genetic determinants of resistance likely to be transmitted on mobile genetic elements and to evaluate relatedness of strains including DNA microarray, multilocus sequence typing, repetitive sequence-based PCR, and hsp60 sequencing typing.

Evaluating 854 swabs from unique children, the overall prevalence of colonization with an MDR Enterobacteriaceae upon admission to the PICU based on β-lactamase gene identification was 4.3% (n=37), including 2.8% ESBLs (n=24), 1.3% pAmpCs (n=11), and 0.2% carbapenemases (n=2). Among 157 pediatric patients contributing 603 subsequent weekly swabs, 6 children (3.8%) acquired an incident MDR Enterobacteriaceae during their PICU stay. One child acquired a pAmpC (E. coli containing blaDHA) related to an isolate from another patient.

Approximately 4% of children admitted to a PICU were colonized with MDR Enterobacteriaceae (based on β-lactamase gene identification) and an additional 4% of children who remained in the PICU for at least 1 week acquired 1 of these organisms during their PICU stay. The acquired MDR Enterobacteriaceae were relatively heterogeneous, suggesting that a single source was not responsible for the introduction of these resistance mechanisms into the PICU setting.

Infect Control Hosp Epidemiol 2016;37:535–543