title: Low-virulence Citrobacter species encode resistance to multiple antimicrobials.
abstract: Citrobacter spp. are gram-negative commensal bacteria that infrequently cause serious nosocomial infections in compromised hosts. They are often resistant to cephalosporins due to overexpression of their chromosomal beta-lactamase. During a recent study of multidrug-resistant Enterobacteriaceae (MDRE) in solid-organ transplant patients, we found that almost half of patients colonized with MDRE carried one or more cefpodoxime-resistant Citrobacter freundii, Citrobacter braakii, or Citrobacter amalonaticus strains. Pulsed-field gel electrophoresis showed that 36 unique strains of Citrobacter were present among 32 patients. Genetic and phenotypic analysis of the resistance mechanisms of these bacteria showed that the extended-spectrum beta-lactamase (ESBL) SHV-5 or SHV-12 was encoded by 8 strains (26%) and expressed by 7 strains (19%). A number of strains were resistant to other drug classes, including aminoglycosides (28%), trimethoprim-sulfamethoxazole (31%), and fluoroquinolones (8%). PCR and DNA analysis of these multiresistant strains revealed the presence of class I integrons, including the first integrons reported for C. braakii and C. amalonaticus. The integrons encoded aminoglycoside resistance, trimethoprim resistance, or both. Despite the prevalence of MDR Citrobacter spp. in our solid-organ transplant patients, only a single infection with a colonizing strain was recorded over 18 months. Low-virulence Citrobacter spp., which can persist in the host for long periods, could influence pathogen evolution by accumulation of genes encoding resistance to multiple antimicrobial classes.
authors.affiliation: The Centre for Infection and Biomaterials Research, Hospital for Sick Children Research Institute. Departments of Surgery. Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Pepperell
authors.forename: J V
authors.initials: JV
authors.lastname: Kus
authors.forename: M A
authors.initials: MA
authors.lastname: Gardam
authors.forename: A
authors.initials: A
authors.lastname: Humar
authors.forename: L L
authors.initials: LL
authors.lastname: Burrows
mesh_terms: D002954:Citrobacter / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity*; D003001:Cloning, Molecular; D016172:DNA Fingerprinting; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000235:genetics; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D006801:Humans; D032023:Integrons / Q000235:genetics; D007525:Isoelectric Focusing; D008826:Microbial Sensitivity Tests; D016377:Organ Transplantation; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D004269:DNA, Bacterial; D001618:beta-Lactamases