# Rising incidence of carbapenem-resistant Citrobacter spp. in a German tertiary-care hospital: epidemiology, clinical impact, and the role of the hospital wastewater system—findings from a six-year molecular study

## TL;DR

This study tracks a growing problem of antibiotic-resistant Citrobacter bacteria in a German hospital, linking their spread to the hospital's wastewater system.

## Contribution

The study reveals that carbapenem-resistant Citrobacter spp. are spreading through genetically diverse strains across multiple hospital departments, with wastewater playing a key role.

## Key findings

- CRC became the most common carbapenem-resistant Enterobacterales at the hospital, increasing from 9.2% to 37.8% of CRE isolates between 2019 and 2024.
- Hospital wastewater was found to contain CRC strains genetically matching patient isolates, indicating its role in dissemination.
- Most CRC cases involved colonization rather than severe infections, with no cases of bacteremia observed.

## Abstract

In recent years, a threatening rise in carbapenem-resistant Citrobacter spp. (CRC) has been observed in various global regions. Sewage systems have repeatedly been suggested as reservoirs. At our tertiary-care hospital in Germany, CRC have become the most frequently detected species among the carbapenem-resistant Enterobacterales (CRE) over the past six years. This study aimed to analyze CRC’s site-specific epidemiological development, assess their clinical significance, and elucidate the potential role of the hospital wastewater system in the observed increase in CRC. A retrospective epidemiological investigation was conducted using Poisson models. Clinical baseline data of affected patients were evaluated. Whole-genome sequencing and a subcluster analysis of 138 CRC patient isolates were performed. The wastewater systems of three clinical wards located in two separate hospital buildings were examined. The annual proportion of CRC in CRE increased from 9.2% in 2019 to 37.8% in 2024 (P < 0.001). 27.5% of isolates were detected in clinical specimens, most frequently in urine samples (52.6%). There were no cases of bacteremia. We identified 26 MLST types and 22 subclusters. Ninety-three percent of isolates had one (77.5%), two (14.7%), or three (0.8%) carbapenemases. Wastewater analysis identified 27 of 37 (73.0%) environmental CRC isolates as genetically consistent with patient-derived strains. Our findings reveal a newly emerging complexity, characterized by the spread of various genetically distinct CRC across several departments of our hospital. While CRC colonization increased, the frequency and severity of infections remained moderate. The hospital wastewater system represents a key factor in CRC’s dissemination.

In this study, we analyzed the significant increase in CRC strains at our tertiary-care hospital over the past six years. Our findings revealed that, unlike classical outbreak scenarios — typically characterized by the clonal expansion of one strain within a single ward or unit — the rising incidence of CRC was driven by the dissemination of numerous genetically diverse strains across multiple departments. The hospital sewage system was identified as a reservoir and plays an important role in the rapid proliferation and dissemination of CRC. The high complexity of the situation presents a new challenge, as transmission pathways are now difficult to trace, hindering effective prevention. Remarkably, the majority of patients affected by CRC were merely colonized, and severe infections were not observed. It remains to be determined whether this pattern reflects a site-specific phenomenon or indicates a broader trend on a European or even global scale.