Genotypic characterization and in vitro activities of tigecycline and polymyxin B for members of the Enterobacteriaceae with decreased susceptibility to carbapenems

Abstract

Carbapenem resistance in members of the Enterobacteriaceae is increasing. To evaluate the effects of tigecycline and polymyxin B against carbapenem-non-susceptible pathogens, 89 representative clinical carbapenem-non-susceptible Enterobacteriaceae isolates were recovered from seven hospitals from four cities in China during 2006-2009: 30 Serratia marcescens, 35 Klebsiella pneumoniae, seven Enterobacter cloacae, six Enterobacter aerogenes, five Escherichia coli, four Citrobacter freundii and two Klebsiella oxytoca isolates. Twenty-eight S. marcescens isolates were indistinguishable. The 35 K. pneumoniae isolates belonged to 12 clonal strains. Among the 89 Enterobacteriaceae isolates, 82 produced KPC-2, seven produced IMP (three produced KPC-2 simultaneously), three did not produce any carbapenemases and nine were deficient in porins. Polymyxin B was much more active than tigecycline against carbapenem-non-susceptible Enterobacteriaceae. The MIC(50) and MIC(90) of imipenem, meropenem, ertapenem, polymyxin B and tigecycline were 8 and 32 µg ml(-1), 8 and 32 µg ml(-1), 16 and 128 µg ml(-1), 0.5 and 16 µg ml(-1), and 4 and 16 µg ml(-1), respectively. Rates of susceptibility to imipenem, meropenem, ertapenem and polymyxin B were 30.0%, 27.5%, 2.5% and 89.2% by CLSI criteria. The rate of susceptibility to tigecycline was 40% and 17.5% by Food and Drug Administration (MIC ≤2 µg ml(-1)) and European Committee on Antimicrobial Susceptibility Testing (MIC ≤1 µg ml(-1)) criteria, respectively. KPC-2- or IMP-producing E. coli transconjugants exhibited reduced susceptibility to carbapenems but were susceptible to polymyxin B and tigecycline with an MIC range of 0.5-2 µg ml(-1), 0.25-2 µg ml(-1), 0.5-4 µg ml(-1), 0.5 µg ml(-1) and 0.5-1 µg ml(-1). In conclusion, carbapenem resistance in Enterobacteriaceae is mainly due to production of KPC-2, and polymyxin B is active for the carbapenem-resistant Enterobacteriaceae.