Whole-Genome Sequencing Identifies In Vivo Acquisition of a blaCTX-M-27-Carrying IncFII Transmissible Plasmid as the Cause of Ceftriaxone Treatment Failure for an Invasive Salmonella enterica Serovar Typhimurium Infection.
We report a case of ceftriaxone treatment failure for bacteremia caused by Salmonella enterica subsp. enterica serovar Typhimurium, due to the in vivo acquisition of a blaCTX-M-27-encoding IncFII group transmissible plasmid. The original β-lactamase-susceptible isolate ST882S was replaced by the resistant isolate ST931R during ceftriaxone treatment. After relapse, treatment was changed to ciprofloxacin, and the patient recovered. Isolate ST931R could transfer resistance to Escherichia coli at 37°C. We used whole-genome sequencing of ST882S and ST931R, the E. coli transconjugant, and isolated plasmid DNA to unequivocally show that ST882S and ST931R had identical chromosomes, both having 206 identical single-nucleotide polymorphisms (SNPs) versus S Typhimurium 14028s. We assembled a complete circular genome for ST931R, to which ST882S reads mapped with no SNPs. ST882S and ST931R were isogenic except for the presence of three additional plasmids in ST931R. ST931R and the E. coli transconjugant were ceftriaxone resistant due to the presence of a 60.5-kb IS26-flanked, blaCTX-M-27-encoding IncFII plasmid. Compared to 14082s, ST931R has almost identical Gifsy-1, Gifsy-2, and ST64B prophages, lacks Gifsy-3, and instead carries a unique Fels-2 prophage related to that found in LT2. ST882S and ST931R both had a 94-kb virulence plasmid showing >99% identity with pSLT14028s and a cryptic 3,904-bp replicon; ST931R also has cryptic 93-kb IncI1 and 62-kb IncI2 group plasmids. To the best of our knowledge, in vivo acquisition of extended-spectrum β-lactamase resistance by S Typhimurium and blaCTX-M-27genes in U.S. isolates of Salmonella have not previously been reported.
University of Colorado Anschutz Medical Campus, Division of Infectious Disease, Aurora, Colorado, USA.
Bruce
B
McCollister
University of Colorado Anschutz Medical Campus, Division of Infectious Disease, Aurora, Colorado, USA.
Cassandra V
CV
Kotter
University of Colorado Anschutz Medical Campus, Division of Infectious Disease, Aurora, Colorado, USA.
Daniel N
DN
Frank
University of Colorado Anschutz Medical Campus, Division of Infectious Disease, Aurora, Colorado, USA.
Taylor
T
Washburn
University of Colorado Anschutz Medical Campus, Department of Immunology and Microbiology, Aurora, Colorado, USA michael.jobling@ucdenver.edu.
Michael G
MG
Jobling
D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D002443:Ceftriaxone / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000627:therapeutic use; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics*; D005260:Female; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D039002:Prophages / Q000235:genetics; D012480:Salmonella Infections / Q000188:drug therapy* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics*; D017211:Treatment Failure; D001618:beta-Lactamases / Q000235:genetics*
D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D002939:Ciprofloxacin; D002443:Ceftriaxone; C477098:CTX-M-27, E coli; D001618:beta-Lactamases
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