Dorottya Nagy | Risk factors for plasmid-mediated hospital outbreaks of CPE

Background
Carbapenemase-producing Enterobacterales (CPE) are critical priority pathogens, epitomising the antimicrobial resistance (AMR) pandemic. Epidemiological studies have evaluated individual-level risk factors contributing to CPE transmission and genomic studies have implicated certain ‘high-risk’ lineages or mobile genetic elements (MGEs) such as plasmids, but a joint epidemiological, microbiological and genomic framework for quantifying the risk of dissemination for any emerging CPE-associated lineage or plasmid is lacking. This systematic review will synthesise epidemiological, microbiological and genomic risk factors for healthcare-associated CPE outbreaks from publicly-available studies to develop such a framework.

Methods
Electronic literature searches (27/11/23-31/01/24) of bibliographic databases, surveillance reports and conference abstracts (search concepts: carbapenemase AND outbreak AND mobile genetic element) are being undertaken. Risk factors will be summarised under three categories: epidemiological (temporal, patient, and hospital characteristics), microbiological (number and identity of carbapenemase-carrying species, lineages, plasmids, transposons, other MGEs, and associated AMR genes) and containment measures (patient screening and isolation, ward cleaning and closure, education and antimicrobial-use change). The main outbreak outcome recorded will be final size, duration, mortality rates (continuous) and success of elimination (binary). Linear and logistic regressions will be performed for continuous and binary outcomes, respectively, to obtain correlation coefficients and odds ratios with 95% CIs for each risk factor-outcome combination. Risk of bias will be assessed using STROBE and ORION guidelines.

Results
969 publications were retrieved from MEDLINE. This list is being supplemented with search results from other information sources before double-screening of abstracts and full-texts. Pilot analyses suggest more recent reports provide more detailed genomic information, although few report comprehensively on all three risk factor categories, and reporting of outbreak outcomes is poorly unified.

Discussion
This systematic review of publicly available CPE outbreak data will evaluate whether commonly reported epidemiological, microbiological and genomic markers can predict outbreak severity. This information can be leveraged to optimise future sampling and genomic analysis as part of future CPE outbreak response.