Diverse carbapenem-resistance mechanisms in 16S rRNA methylase-producing Acinetobacter baumannii

摘要

Multidrug-resistant Acinetobacter baumannii has become a global problem. This study characterized amikacin-resistant A. baumannii isolated from eight patients during April 2010–March 2011 in our university hospital and examined the possible mechanisms in three cases in which carbapenem susceptibility changed to carbapenem resistance during treatment of the patients. The armA gene, which is one of the 16S rRNA methylase genes and is associated with high MICs of aminoglycosides, was positive in all isolates. The bla OXA-51 gene and ISAba1 and ISAba1-bla ADC were positive in all isolates, but ISAba1-bla OXA-51 was positive in only three isolates. The CarO outer-membrane protein was lost in one isolate. In the first case, both the susceptible and the resistant isolates were positive for ISAba1-bla OXA-51, but the expression of the bla ADC gene was increased 3.1-fold in the carbapenem-resistant isolate of the pair. In the second case, the carbapenem-resistant strain became positive for ISAba1-bla OXA-51, resulting in 21.5-fold increased expression of bla OXA-51, compared to the carbapenem-susceptible strain of the pair. In the third case, the carbapenemase genes remained negative despite the carbapenem resistance, but the expression of the adeB gene was increased 4.6-fold after acquisition of carbapenem resistance. Multilocus sequence typing analysis of two isolates showing representative pulsed-field gel electrophoresis patterns demonstrated that both isolates were classified to sequence type 2 (ST2). These results showed that the 16S rRNA methylase-producing A. baumannii, initially susceptible to carbapenem, acquired carbapenem resistance via diverse mechanisms.