Characterization of a Novel AmpC β-Lactamase Produced by a Carbapenem-Resistant Cedecea davisae Clinical Isolate

Abstract

A Cedecea davisae isolate, which was intermediate or resistant to third-generation cephalosporins and carbapenems, was recovered from a urine sample. Susceptibility testing, isoelectric focusing, and analysis of outer membrane proteins showed that AmpC ␤-lactamase expression combined with porin deficiency accounted for the carbapenem resistance. A cloning experiment followed by phenotypic and enzymatic characterization identified a novel class C enzyme that was phylogenetically and biochemically close to the chromosome-borne ␤-lactamases of the genera Enterobacter and Citrobacter. C edecea davisae is an enterobacterium that can be responsible for human infections (1-4). Cephalothin resistance has been already reported in this species, but the mechanism has not been yet elucidated (5).The aim of this work was to identify the mechanisms of resistance of a C. davisae clinical isolate that was resistant to almost all ␤-lactams. It was recovered from a 77-year-old woman who was hospitalized in an intensive care unit of the teaching hospital of Amiens. Eighteen days after a cardiac valve replacement, the patient had a hemorrhagic shock due to retroperitoneal bleeding. The urine sample recovered after nephrostomy was sent to the Laboratory of Bacteriology. It grew a Gram-negative rod (10 7 CFU/ml) that was identified as C. davisae FUR by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (Shimadzu, Marne la Vallée, France) and 16S rRNA sequencing. The patient was started successfully on intravenous ciprofloxacin for 7 days.

Characterization of a Novel Chromosomal Class C β-Lactamase, YOC-1, and Comparative Genomics Analysis of a Multidrug Resistance Plasmid in Yokenella regensburgei W13

“…This discrepancy between phenotypic and biochemical approaches could also result from the low but not zero deacylation rate of AmpC β-lactamases with those compounds. A similar phenomenon was observed for CDA-1, whose host showed resistance to ertapenem, but the β-lactamase did not have hydrolytic activity against ertapenem (Ammenouche et al, 2014).…”

Altered Outer Membrane Transcriptome Balance with AmpC Overexpression in Carbapenem-Resistant Enterobacter cloacae

“…The authors indicated comorbidity of OM permeability disorders with the presence of AmpC and/or extended-spectrum β-lactamases (Hasdemir et al, 2004; Drew et al, 2013; Ammenouche et al, 2014). Acquired carbapenemase participation in the development of resistance to carbapenems among Enterobacteriaceae was estimated in a report published by Robert et al (2014).…”

Molecular Characterization of Carbapenem-Nonsusceptible Enterobacterial Isolates Collected during a Prospective Interregional Survey in France and Susceptibility to the Novel Ceftazidime-Avibactam and Aztreonam-Avibactam Combinations

“…AmpC enzymes appeared to contribute greatly to carbapenem resistance in our collection. The carbapenem-hydrolyzing activity of class C ␤-lactamases has been reported previously (1,7). This activity could be attributable, at least in part, to the asparagine residue at position 346, which plays a role in placing the acyl enzyme intermediate of extended-spectrum cephalosporins (ESCs) in a position that is more competent for hydrolytic attack (1,21).…”

“…However, few data describe the in vitro activity of this combination against porin-deficient enterobacterial isolates. To the best of our knowledge, only two articles showed the in vitro efficiency of this combination against well-characterized porin-deficient enterobacterial clinical isolates, namely, Cedecea davisae FUR and K. pneumoniae C2/pMG247 (7,39). Livermore et al also reported the activity of the ceftazidime-avibactam combination against a few ertapenem-resistant enterobacterial isolates, but these isolates were not characterized on the molecular level (40).…”