Elias Eger (Greifswald / DE), Michael Schwabe (Greifswald / DE), Timo Homeier-Bachmann (Greifswald / DE), Augustina A. Sylverken (Kumasi / GH), Karsten Becker (Greifswald / DE), Helmut Fickenscher (Kiel / DE), Andi Krumbholz (Kiel / DE), Dennis Nurjadi (Lübeck / DE), Stefan E. Heiden (Greifswald / DE), Katharina Schaufler (Greifswald / DE)
Enterobacterales, e.g., Escherichia coli (EC) and Klebsiella pneumoniae (KP), stand out for their ability to evolve and acquire resistance to last-line antibiotics such as carbapenems, contributing to difficult-to-treat infections. Cefiderocol (FDC) was developed to combat such multidrug-resistant (MDR) strains by using a mechanism that bypasses common resistance mechanisms. Unfortunately, as with most new drugs, resistance to FDC has been reported with increasing frequency, always associated with hospitalization and antibiotic therapy. However, little is known about the prevalence of FDC-resistant EC and KP beyond the hospital walls. Our studies aimed to fill this gap by investigating the presence of these pathogens in a One Health context.
We sampled surface water from different sites in a Western European (Germany) and a Sub-Saharan African (Ghana) setting. Bacteria were initially selected for their MDR phenotype, whole genome sequenced and subsequently tested for FDC resistance. In addition, strains from various human, animal, and environmental sources from our strain collection were systematically tested for FDC resistance.
We collected a total of 116 MDR EC and 28 MDR KP. EC strains with phenotypic resistance to FDC were present in both sets of water samples. Interestingly, typical mutations described in the literature as resistance markers (e.g., ompC) were not confirmed by genomic analysis. Knock-in and knock-out studies are ongoing. In addition, we identified FDC-resistant, convergent KP strains of sequence type 307 in our strain collection that were isolated during a clonal outbreak in Germany that preceded the clinical use of FDC. Of note, the underlying mutation type in the cirA gene has not yet been described in this context.
Our research has revealed the emergence of FDC-resistant strains in surface waters in Germany and Ghana. More importantly, FDC resistance is not a recent phenomenon and may have predated the clinical use. These findings highlight the need for comprehensive One Health studies that integrate genomic and epidemiologic data to effectivly monitor and manage antimicrobial resistance at the human-animal-environmental interface.