Epidemiological, microbiological, and genomic risk factors for healthcare-associated Carbapenemase producing Enterobacterales (CPE) outbreaks: A systematic review

BackgroundHealthcare-associated carbapenemase-producing Enterobacterales (CPE) outbreaks are a major healthcare challenge. Epidemiological studies have identified patient-level risk factors for CPE transmission, and genomic studies have highlighted high-risk lineages or mobile genetic elements (MGEs); however, a unified dissemination risk-prediction framework is lacking. ObjectivesTo synthesise available data on epidemiological, microbiological and genomic risk factors to quantify healthcare-associated CPE outbreak potential. MethodsO_ST_ABSDataC_ST_ABSSix bibliographic databases and other sources were searched ( carbapenemase AND outbreak AND MGE; [≤]31/01/24). Data were extracted on primary (patients infected/colonised) and secondary (outbreak duration/resolution, mortality) outcomes, and risk/protective factors including epidemiological, microbiological/genomic and infection control measures. Study eligibilityStudies reporting healthcare-associated CPE outbreaks involving MGE-associated IMP/KPC/NDM/OXA-48-like/VIM carbapenemases confirmed by whole-genome sequencing. Study qualityReporting quality was assessed against the ORION checklist (random subset). Data synthesisAfter descriptive summaries, multivariable linear mixed effect modelling was used to estimate associations between risk/protective factors and outbreak size. Results179 records (272 outbreaks) were included from 3,188 screened (41 countries, 2004-2023), affecting median 10 patients (IQR=5-27, range=2-223), and lasting 12 months (IQR=5-30, range=1 day-16 years). Data on outbreak size (primary outcome) was 99.6% complete (271/272) but more limited for secondary outcomes (29-97% complete) and risk/protective factors (70/91 factors had [≥]10% missingness). 39% (107/272) of outbreaks involved MGE-mediated transmission, which is a potential underestimate as 66% (104/157) of reports used clonal outbreak definitions. The involvement of more institutions (adjusted relative outbreak size: 1.10 per institution [95% CI: 1.04-1.16];p=0.001), and more Enterobacterales sequence types (1.04 per sequence type [1.01-1.08];p=0.011), were associated with larger outbreaks. Reporting quality assessment (n=98 studies) revealed adequate reporting on median 11/19 relevant ORION items (IQR=8-13; range=1-18). ConclusionsHeterogenous/incomplete reporting of CPE outbreaks precludes integrated risk evaluation based on epidemiological, microbiological, and genomic factors. Systematic sampling, sequencing and epidemiological metadata reporting may strengthen data quality for quantifying healthcare-associated CPE dissemination risk.