Induction of plasmid-mediated AmpC β-lactamase DHA-1 by piperacillin/tazobactam and other β-lactams in Enterobacteriaceae

Chromosomal AmpC β-lactamase induction by several types of β-lactams has been reported, but not enough data are available on DHA-1 β-lactamase, a plasmid-mediated AmpC β-lactamase. Therefore, we evaluated the DHA-1 β-lactamase induction by various antibiotics including piperacillin/tazobactam (PIP/TZB) in this study. Six strains (Enterobacter cloacae 2 strains, Citrobacter freundii 1 strain, Serratia marcescens 2 strain, and Morganella morganii 1 strain) possessing chromosomal inducible AmpC β-lactamase were used as controls. Four strains (Escherichia coli 2 strains, Klebsiella pneumoniae 1 strain, and C. koseri 1 strain) possessing DHA-1 β-lactamase were used. The β-lactamase activities were determined by a spectrophotometer using nitrocefin. β-lactamase induction by PIP, PIP/TZB was not observed in any strains and β-lactamase induction by third- and fourth-generation cephems was not observed in most strains. The induction ratios of the chromosomal AmpC β-lactamase in the reference group by PIP/TZB were <1.51, and those of the DHA-1 β-lactamase were <1.36, except for K. pneumoniae Rkp2004 (2.22). The β-lactamase induction by first- and second-generation cephems, flomoxef, and carbapenem differed in each strain. Cefmetazole (CMZ) strongly induced β-lactamase. This study demonstrated that the induction of DHA-1 β-lactamase was similar to that of chromosomal AmpC using various Enterobacteriaceae, although the induction of β-lactamase in both groups by PIP/TZB was low. We also reported that the induction of PIP/TZB, a β-lactamase inhibitor combination antibiotic, against various AmpC-producing Enterobacteriaceae, including DHA-1 producers, was low.