AmpC hyperproduction in a Cedecea davisae implant-associated bone infection during treatment – a case report and therapeutic implications

Notter, Julia, Seiffert, Salome N., Zimmermann-Kogadeeva, Maria, Bösch, Anja, Wenger, Robert, Strahm, Carol, Frischknecht, Manuel, Livermore, David M. ORCID: https://orcid.org/0000-0002-9856-3703 and Babouee Flury, Baharak (2022) AmpC hyperproduction in a Cedecea davisae implant-associated bone infection during treatment – a case report and therapeutic implications. BMC Infectious Diseases, 22. ISSN 1471-2334

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Abstract

Background: Data on antimicrobial resistance mechanisms are scanty for Cedecea spp., with very variable antibiotic resistance patterns documented. Here we report the first in vivo resistance evolution of a C. davisae clinical isolate in a patient with a complex hand trauma and provide insight in the resistance mechanism, leading to therapeutic implications for this pathogen. Case presentation: Cedecea davisae was isolated from a patient with hand trauma during a first surgical debridement. Six days after primary surgical treatment and under antimicrobial treatment with amoxicillin-clavulanic acid and later cefepime, follow up cultures yielded C. davisae which demonstrated a resistance development. The susceptible parental isolate and its resistant derivative were characterized by whole genome sequencing, ampC, ompC and ompF by RT- PCR. The resistant derivative demonstrated an A224G SNP in ampD, the transcriptional regulator of ampC, leading to a His75Arg change in the corresponding AmpD protein. AmpC transcription of the resistant derivative was 362-times higher than the susceptible isolate. Transcription levels of ompF and ompC were 8.5-fold and 1.3-fold lower, respectively, in the resistant derivative. Downregulation of OmpF putatively resulted from a mutation in the presumed promoter region upstream of the dusB-Fis operon, a proposed regulator for ompF. Conclusions: This case demonstrates the in vivo resistance development of C. davisae within 7 days similar to that of the members of the Enterobacter cloacae complex. Our findings add valuable information for future therapeutic management of these opportunistic pathogens as they warrant the same empirical treatment as AmpC producers.

Item Type: Article
Additional Information: Funding Information: This study was funded by a research grant of the Medical Research Centre of Kantonsspital St. Gallen, Switzerland. The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Uncontrolled Keywords: ampc,c. davisae implant-associated bone infection,case report,cedecea davisae,cefepime,hyperproducing,resistance evolution,infectious diseases ,/dk/atira/pure/subjectarea/asjc/2700/2725
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023)
Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health
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Depositing User: LivePure Connector
Date Deposited: 23 Dec 2021 16:30
Last Modified: 23 Oct 2022 03:26
URI: https://ueaeprints.uea.ac.uk/id/eprint/82821
DOI: 10.1186/s12879-021-07000-y

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