# A New Challenge of Antibiotic-Resistant Bacteria: Carbapenem-Resistant Enterobacter cloacae Complex in a One Health Perspective

## TL;DR

This paper reviews the growing threat of carbapenem-resistant Enterobacter cloacae complex and its spread across human, animal, and environmental settings.

## Contribution

The paper provides a One Health perspective on CRECC, emphasizing its epidemiology and resistance mechanisms across interconnected ecosystems.

## Key findings

- CRECC is increasingly detected in hospitals and is associated with various infections.
- Carbapenem resistance is primarily due to genes like blaNDM, blaKPC, and blaOXA-48-like on conjugative plasmids.
- CRECC and resistance genes are found in animals, food, and environments, suggesting interconnected spread.

## Abstract

Carbapenem-resistant Enterobacter cloacae Complex (CRECC) has emerged as an important multidrug-resistant pathogen in healthcare settings, although it has historically received less attention than carbapenem-resistant Klebsiella pneumoniae and other major carbapenem-resistant Enterobacterales (CRE). Recent epidemiological reports from several regions indicate increasing detection rates of CRECC in tertiary hospitals, where it is associated with bloodstream infections, pneumonia, urinary tract infections, and prolonged hospitalization. The dissemination of carbapenemase genes, particularly blaNDM, blaKPC, and blaOXA-48-like, carried predominantly on conjugative plasmids (e.g., IncFII, IncX3, IncL), represents the primary resistance mechanism, often accompanied by porin loss and efflux pump overexpression. High-risk clones such as ST171 and ST78 contribute to nosocomial persistence and outbreak potential. Beyond clinical settings, CRECC and related resistance determinants have been reported in companion animals, livestock, food products, wastewater systems, and natural aquatic environments. Although most available studies examine these sectors separately, the recurring detection of genetically related resistance genes and plasmid types suggests potential epidemiological links that warrant integrated surveillance. Environmental reservoirs, particularly hospital effluents and wastewater treatment systems, may facilitate the maintenance and dissemination of resistance genes. This review synthesizes current evidence on the epidemiology, resistance mechanisms, and evolutionary dynamics of CRECC in human, animal, and environmental contexts under a One Health framework. A better understanding of its ecological distribution and genetic plasticity is essential to inform coordinated surveillance strategies and mitigate the public health risks associated with the continued spread of carbapenem resistance.