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This study investigates cefiderocol-resistant bacteria in wastewater from six German tertiary care hospitals. A total of 36 samples were analysed using a culture-dependent approach involving cefiderocol pre-enrichment, yielding 97 cefiderocol-resistant isolates\u2014primarily <jats:italic>Enterobacter roggenkampii<\/jats:italic>, <jats:italic>Klebsiella oxytoca<\/jats:italic>, <jats:italic>Serratia marcescens<\/jats:italic>, and <jats:italic>Citrobacter farmeri<\/jats:italic>. Most isolates exhibited high minimum inhibitory concentrations against cefiderocol and resistance to multiple antibiotics. Resistance rates were lower for meropenem-vaborbactam (10.3%) and imipenem-relebactam (33.0%), while all isolates remained susceptible to aztreonam-avibactam. Whole-genome sequencing of 79 isolates revealed a diverse resistome, with 78.5% (62\/79) carrying carbapenemase genes. Some isolates harbored up to six distinct \u03b2-lactamase genes, including combinations of extended-spectrum \u03b2-lactamases (ESBLs), AmpC \u03b2-lactamases, and one or multiple carbapenemases\u2014such as as <jats:italic>bla<\/jats:italic>\n            <jats:sub>OXA\u221248<\/jats:sub> co-occurring with <jats:italic>bla<\/jats:italic>\n            <jats:sub>NDM\u22121<\/jats:sub> or <jats:italic>bla<\/jats:italic>\n            <jats:sub>VIM\u22121<\/jats:sub>. In addition, biocide and heavy metal resistance genes were prevalent, highlighting bacterial adaptation to harsh environments. Plasmid profiling showed significant interspecies variation, with <jats:italic>C. farmeri<\/jats:italic> and <jats:italic>K. oxytoca<\/jats:italic> displaying the highest plasmid loads. Across all isolates, 38 unique plasmid incompatibility types were detected, 18 of which were species-specific. These findings highlight the multidrug-resistant nature of wastewater-derived pathogens and the importance of monitoring resistance dissemination in healthcare environments.<\/jats:p>","DOI":"10.1038\/s41598-025-17379-2","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T17:23:00Z","timestamp":1756315380000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cefiderocol-resistant pathogens in German hospital wastewater: a reservoir for multidrug resistance"],"prefix":"10.1038","volume":"15","author":[{"given":"Tim","family":"Erler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Carlsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Dengler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Andre","family":"Hammerl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas J.","family":"Stroehlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes K.","family":"Knobloch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"L\u00fcbbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cihan","family":"Papan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Schwanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Zweigner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurag Kumar","family":"Bari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil Britto","family":"Xavier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W. 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