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The present study aimed to develop a rational therapy based on the genetic epidemiology, molecular mechanism evaluation and in vitro antibiotic combinations activity in multidrug-resistant Acinetobacter baumannii (MDRAB). MDRAB was screened by the Kirby-Bauer method. The random amplified polymorphic DNA technique was used to establish genetic fingerprinting, and a series of resistance genes were detected by polymerase chain reaction. Antimicrobial agents including amikacin (AK), cefoperazone/sulbactam (SCF I/II), meropenem (MEM), minocycline (MINO) and ciprofloxacin (CIP) were used to determine the minimum inhibitory concentrations (MICs) and interactions between antibiotics by the broth microdilution method and chequerboard assays. In total, 34 MDRAB strains were isolated and classified into 8 phenotypes A-H, according to their general drug susceptibilities. A total of 4 major genotypes (I-IV) were clustered at 60% a genotypic similarity threshold. High positive rates of β-lactamase TEM-1 , topoisomerase IV, oxacillinase ( OXA )-23, AdeB family multidrug efflux RND transporter adeB , β-lactamase AmpC , class 1 integrons ( Int-1 ), 16S rRNA methylase rmtA , phosphotransferase aph (3), 16S rRNA methyltransferase armA were presented to exceed 90%, acetylyltransferase aac(3)-I , aac(6'-I , ant(3″)-I , 16S rRNA methylase rmtB , oxacillinase OXA-24 and metallo-β-lactamase IMP-5 genes demonstrated positive rates of 29.4-85.29%, while adeRS two-component system was not observed in any strain. MEM+SCF I or SCF II primarily exhibited synergistic effects. AK+SCF I, AK+SCF II, MINO+SCF I, MINO+SCF II, MINO+CIP and MINO+MEM primarily presented additive effects. AK+CIP demonstrated 70.59% antagonism. The antibacterial activity of SCF I was superior compared with that of SCF II. The results indicated the polyclonal genetic epidemiological trend of MDRAB in the Second Xiangya Hospital, and verified the complexity of genetic resistance. In addition, combinations suggested to be efficacious were MEM+SCF I and MEM+SCF II, which were more effective compared with other combinations for the management of MDRAB infection.

oncology letters

Genetic characterization and inï¿½vitro activity of antimicrobial combinations of multidrug-resistant Acinetobacterï¿½baumannii from a general hospital in China