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Antimicrobial Agents and Chemotherapy, November 2002, p. 3555-3560, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3555-3560.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Low-Virulence Citrobacter Species Encode Resistance to Multiple Antimicrobials

C. Pepperell,1 J. V. Kus,1 M. A. Gardam,2 A. Humar,2 and L. L. Burrows1,3*

The Centre for Infection and Biomaterials Research, Hospital for Sick Children Research Institute,1 Departments of Surgery,2 Medicine, University of Toronto, Toronto, Ontario, Canada3

Received 4 March 2002/ Returned for modification 19 July 2002/ Accepted 16 August 2002

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 ß-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 ß-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.

* Corresponding author. Mailing address: Centre for Infection and Biomaterials Research, Hospital for Sick Children, 7142A-555 University Ave., Toronto, ON M5G 1X8, Canada. Phone: (416) 813-6293. Fax: (416) 813-6461. E-mail: lori.burrows{at}sickkids.ca.

Antimicrobial Agents and Chemotherapy, November 2002, p. 3555-3560, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3555-3560.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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