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

Background Healthcare-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.

Objectives To synthesise available data on epidemiological, microbiological and genomic risk factors to quantify healthcare-associated CPE outbreak potential.

Data Six 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 eligibility Studies reporting healthcare-associated CPE outbreaks involving MGE-associated IMP/KPC/NDM/OXA-48-like/VIM carbapenemases confirmed by whole-genome sequencing.

Study quality Reporting quality was assessed against the ORION checklist (random subset).

Data synthesis After descriptive summaries, multivariable linear mixed effect modelling was used to estimate associations between risk/protective factors and outbreak size.

Results 179 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).

Conclusions Heterogenous/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.