Molecular Epidemiology and Mechanism of Sulbactam Resistance in Acinetobacter baumannii Isolates with Diverse Genetic Backgrounds in China

Abstract

Sulbactam is a plausible option for treating <i>Acinetobacter</i> infections because of its intrinsic antibacterial activity against the members of the <i>Acinetobacter</i> genus, but the mechanisms of sulbactam resistance have not been fully studied in <i>Acinetobacter baumannii</i> In this study, a total of 2,197 clinical <i>A. baumannii</i> isolates were collected from 27 provinces in China. Eighty-eight isolates with various MICs for sulbactam were selected on the basis of their diverse clonality and underwent multilocus sequence typing (MLST), antimicrobial susceptibility testing, and resistance gene screening. The copy number and relative expression of <i>bla</i>_TEM-1D and <i>ampC</i> were measured via quantitative PCR and quantitative reverse transcription-PCR, respectively. The genetic structure of multicopy <i>bla</i>_TEM-1D was determined using the whole-genome sequencing technology. The cefoperazone-sulbactam resistance rate of the 2,197 isolates was 39.7%. The rate of positivity for <i>bla</i>_TEM-1D or IS<i>Aba1-ampC</i> in the sulbactam-nonsusceptible group (64.91% and 78.95%, respectively) was significantly higher than that in the sulbactam-susceptible group (0% and 0%, respectively; <i>P</i> < 0.001). The MIC of sulbactam (<i>P</i> < 0.001) varied considerably between the groups expressing <i>ampC</i> with or without upstream IS<i>Aba1</i> Notably, the genetic structure of the multicopy <i>bla</i>_TEM-1D gene in strain ZS3 revealed that <i>bla</i>_TEM-1D was embedded within four tandem copies of the cassette IS<i>26-bla</i>_TEM-1D-Tn<i>3</i>-IS<i>26</i> Therefore, <i>bla</i>_TEM-1D and IS<i>Aba1-ampC</i> represent the prevalent mechanism underlying sulbactam resistance in clinical <i>A. baumannii</i> isolates in China. The structure of the four tandem copies of <i>bla</i>_TEM-1D first identified may increase sulbactam resistance.