Display options
Share it on

BMC Infect Dis. 2022 Jan 06;22(1):33. doi: 10.1186/s12879-021-07000-y.

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

BMC infectious diseases

Julia Notter, Salome N Seiffert, Maria Zimmermann-Kogadeeva, Anja Bösch, Robert Wenger, Carol Strahm, Manuel Frischknecht, David M Livermore, Baharak Babouee Flury

Affiliations

  1. Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland. [email protected].
  2. Division of Human Microbiology, Centre for Laboratory Medicine, St. Gallen, Switzerland.
  3. Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
  4. Medical Research Centre, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  5. Division of Hand, Plastic and Reconstructive Surgery, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  6. Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  7. Norwich Medical School, University of East Anglia, Norwich, UK.

PMID: 34991516 PMCID: PMC8734214 DOI: 10.1186/s12879-021-07000-y

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.

© 2021. The Author(s).

Keywords: AmpC; C. davisae implant-associated bone infection; Case report; Cedecea davisae; Cefepime; Hyperproducing; Resistance evolution

References

  1. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2383-90 - PubMed
  2. Antimicrob Agents Chemother. 2014 Nov;58(11):6942-5 - PubMed
  3. Am J Case Rep. 2013 Jun 24;14:216-8 - PubMed
  4. Methods. 2001 Dec;25(4):402-8 - PubMed
  5. Brief Bioinform. 2019 Jul 19;20(4):1160-1166 - PubMed
  6. Bioinformatics. 2014 Jul 15;30(14):2068-9 - PubMed
  7. Int J Infect Dis. 2020 Nov;100:461-469 - PubMed
  8. Clin Microbiol Rev. 2009 Jan;22(1):161-82, Table of Contents - PubMed
  9. Case Rep Infect Dis. 2018 Jul 11;2018:7520527 - PubMed
  10. Bioinformatics. 2009 May 1;25(9):1189-91 - PubMed
  11. J Bacteriol. 2011 Jan;193(2):429-40 - PubMed

Publication Types