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 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.

In silico Functional Annotation and Characterization of Hypothetical Proteins in Cedecea neteri SSMD04: Insights into Pathogenicity and Antibiotic Resistance

“…Clinical strains of Cedecea species exhibit natural resistance to various antimicrobial agents such β-lactams and colistin, which tend to confer the behavior of an emerging opportunistic human pathogen (Thompson and Sharkady 2021). Studies have reported that Cedecea encodes genes for antimicrobial resistance, but the exact proteins encoding such genes are not known (Thompson and Sharkady 2021;Notter et al 2022;Ginn et al 2018) In 2015, a previously undiscovered species from the genus Cedecea, specifically identified as Cedecea neteri SSMD04, was first isolated from pickled mackerel sashimi (Tan et al 2015). C. neteri SSMD04 is a gram-negative, bacillus that is found relatively rare in nature, but was recently identified as the infectious agent of a urinary tract infection in a pregnant female with polyhydramnios (Ahmad et al 2021).…”