Intermediate resistance development in Acinetobacter baumannii in vitro and analysis of bacterial respiratory

Abstract:

[Background] Acinetobacter baumannii is an important pathogen of nosocomial infection, which has attracted much attention due to its high drug resistance rate and difficulty in treatment. However, the cross-resistance and the factors related to drug resistance of this bacterium have not been fully elucidated. [Objective] In order to study the cross-resistance and the differences of respiratory oxygen consumption between Acinetobacter baumannii resistant to meropenem or tigecycline and Acinetobacter baumannii sensitive to them, Acinetobacter baumannii was intermediated in vitro with meropenem or tigecycline. [Methods] Meropenem and tigecycline susceptible Acinetobacter baumannii ATCC19606 was induced resistance in vitro, and sequenced PCR products of 16S rRNA of strains before and after drug induction. The minimal inhibitory concentrations (MIC) of meropenem, imipenem, tigecycline, amikacin, cefepime and levofloxacin were determined by a broth microdilution method. Bacterial respiration before and after drug induction, expressed as oxygen consumption rate, was quantified using Seahorse XFe96 extracellular flux analyzer. [Results] Through a 88 d in vitro induction experiment, strain of Acinetobacter baumannii ATCC19606 resistant to meropenem or tigecycline was obtained, respectively. Meropenem-resistant Acinetobacter baumannii ATCC19606 was still sensitive to tigecycline, imipenem, amikacin and levofloxacin, but was cross-resistant to cefepime. Tigecycline-resistant Acinetobacter baumannii ATCC19606 was still sensitive to all antimicrobial agents tested. After Acinetobacter baumannii ATCC19606 was induced by meropenem or tigecycline respectively, the oxygen consumption rate decreased, and the difference was statistically significant. [Conclusion] The use of meropenem may not only induce resistance to meropenem in Acinetobacter baumannii ATCC19606, but also may cause cross-resistance of the bacterium to one or more other antimicrobial agents. The oxygen consumption rate of Acinetobacter baumannii ATCC19606 decreased after its resistance to meropenem or tigecycline, suggesting that the decrease in oxygen consumption rate may be one of the factors contributing to the resistance of this bacterium.

Key words:Acinetobacter baumannii, Bacterial respiration, Tigecycline, Meropenem, Resistance