Of 384 Salmonella isolates collected from 1997 to 2000 in a university hospital in Taiwan, six ceftriaxone-resistant isolates of Salmonella enterica serovar Typhimurium were found in two patients in 2000. The resistance determinants were on conjugative plasmids that encoded a CMY-2-like cephalosporinase. During the study period, the proportion of CMY-2-like enzyme producers among Escherichia coli increased rapidly from 0.2% in early 1999 to >4.0% in late 2000. Klebsiella pneumoniae isolates producing a CMY-2-like beta-lactamase did not emerge until 2000. The presence of bla(CMY)-containing plasmids with an identical restriction pattern from Salmonella, E. coli, and K. pneumoniae isolates was found, which suggests interspecies spread and horizontal transfer of the resistance determinant. Various nosocomial and community-acquired infections were associated with the CMY-2-like enzyme producers. Our study suggests that the spread of plasmid-mediated CMY-2-like beta-lactamases is an emerging threat to hospitalized patients and the public in Taiwan.