AmpC hyperproduction in a Cedecea davisae implant-associated bone infection during treatment: a case report and therapeutic implications
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 insigh...
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12879-021-07000-y |
| _version_ | 1818963979988369408 |
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| author | Julia Notter Salome N. Seiffert Maria Zimmermann-Kogadeeva Anja Bösch Robert Wenger Carol Strahm Manuel Frischknecht David M. Livermore Baharak Babouee Flury |
| author_facet | Julia Notter Salome N. Seiffert Maria Zimmermann-Kogadeeva Anja Bösch Robert Wenger Carol Strahm Manuel Frischknecht David M. Livermore Baharak Babouee Flury |
| author_sort | Julia Notter |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T12:53:50Z |
| format | Article |
| id | doaj.art-6f533dfcffe34b95b6dc490e2147bef1 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-20T12:53:50Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-6f533dfcffe34b95b6dc490e2147bef12022-12-21T19:40:06ZengBMCBMC Infectious Diseases1471-23342022-01-012211710.1186/s12879-021-07000-yAmpC hyperproduction in a Cedecea davisae implant-associated bone infection during treatment: a case report and therapeutic implicationsJulia Notter0Salome N. Seiffert1Maria Zimmermann-Kogadeeva2Anja Bösch3Robert Wenger4Carol Strahm5Manuel Frischknecht6David M. Livermore7Baharak Babouee Flury8Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. GallenDivision of Human Microbiology, Centre for Laboratory MedicineGenome Biology Unit, European Molecular Biology Laboratory (EMBL)Medical Research Centre, Kantonsspital St. GallenDivision of Hand, Plastic and Reconstructive Surgery, Kantonsspital St. GallenDivision of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. GallenDivision of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. GallenNorwich Medical School, University of East AngliaDivision of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. GallenAbstract 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.https://doi.org/10.1186/s12879-021-07000-yCedecea davisaeAmpCHyperproducingCefepimeResistance evolutionCase report |
| spellingShingle | Julia Notter Salome N. Seiffert Maria Zimmermann-Kogadeeva Anja Bösch Robert Wenger Carol Strahm Manuel Frischknecht David M. Livermore Baharak Babouee Flury AmpC hyperproduction in a Cedecea davisae implant-associated bone infection during treatment: a case report and therapeutic implications BMC Infectious Diseases Cedecea davisae AmpC Hyperproducing Cefepime Resistance evolution Case report |
| title | AmpC hyperproduction in a Cedecea davisae implant-associated bone infection during treatment: a case report and therapeutic implications |
| title_full | AmpC hyperproduction in a Cedecea davisae implant-associated bone infection during treatment: a case report and therapeutic implications |
| title_fullStr | AmpC hyperproduction in a Cedecea davisae implant-associated bone infection during treatment: a case report and therapeutic implications |
| title_full_unstemmed | AmpC hyperproduction in a Cedecea davisae implant-associated bone infection during treatment: a case report and therapeutic implications |
| title_short | AmpC hyperproduction in a Cedecea davisae implant-associated bone infection during treatment: a case report and therapeutic implications |
| title_sort | ampc hyperproduction in a cedecea davisae implant associated bone infection during treatment a case report and therapeutic implications |
| topic | Cedecea davisae AmpC Hyperproducing Cefepime Resistance evolution Case report |
| url | https://doi.org/10.1186/s12879-021-07000-y |
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