Salmonellosis is one of the most common causes of
food-borne disease in the United States. Increasing antimicrobial resistance and corresponding increases in virulence present serious challenges. Currently, empirical
therapy for invasive Salmonella enterica
infection includes either
ceftriaxone or
ciprofloxacin (E. L. Hohmann, Clin. Infect. Dis. 32:263-269, 2001). The
bla(CMY-2) gene confers resistance to
ceftriaxone, the antimicrobial of choice for pediatric patients with invasive Salmonella enterica
infections, making these
infections especially dangerous (J. M. Whichard et al., Emerg. Infect. Dis. 11:1464-1466, 2005). We hypothesized that bla(CMY-2)-positive Salmonella enterica would exhibit increased MICs to multiple
antimicrobial agents and increased resistance gene expression following exposure to
ceftriaxone using a protocol that simulated a patient treatment in vitro. Seven Salmonella enterica strains survived a simulated patient treatment in vitro and, following treatment, exhibited a significantly increased
ceftriaxone MIC. Not only would these isolates be less responsive to further
ceftriaxone treatment, but because the
bla(CMY-2) genes are commonly located on large, multidrug-resistant plasmids, increased expression of the
bla(CMY-2) gene may be associated with increased expression of other drug resistance genes located on the plasmid (N. D. Hanson and C. C. Sanders, Curr. Pharm. Des. 5:881-894, 1999). The results of this study demonstrate that a simulated patient treatment with
ceftriaxone can alter the expression of antimicrobial resistance genes, including
bla(CMY-2) and floR in S. enterica serovar Typhimurium and S. enterica serovar Newport. Additionally, we have shown increased MICs following a simulated patient treatment with
ceftriaxone for
tetracycline,
amikacin,
ceftriaxone, and
cefepime, all of which have resistance genes commonly located on CMY-2 plasmids. The increases in resistance observed are significant and may have a negative impact on both public health and antimicrobial resistance of Salmonella enterica.