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Objective:  To investigate the  in vitro  and  in vivo  antibacterial activities of tigecycline and other 13 common antimicrobial agents, alone or in combination, against multi-drug resistant  Acinetobacter baumannii .   Methods:  An  in vitro  susceptibility test of 101  A. baumannii  was used to detect minimal inhibitory concentrations (MICs). A mouse lung infection model of multi-drug resistant  A. baumannii , established by the ultrasonic atomization method, was used to define  in vivo  antimicrobial activities.   Results:  Multi-drug resistant  A. baumannii  showed high sensitivity to tigecycline (98% inhibition), polymyxin B (78.2% inhibition), and minocycline (74.2% inhibition). However, the use of these antimicrobial agents in combination with other antimicrobial agents produced synergistic or additive effects.  In vivo  data showed that white blood cell (WBC) counts in drug combination groups C (minocycline + amikacin) and D (minocycline + rifampicin) were significantly higher than in groups A (tigecycline) and B (polymyxin B) ( P  < 0.05), after administration of the drugs 24 h post-infection. Lung tissue inflammation gradually increased in the model group during the first 24 h after ultrasonic atomization infection; vasodilation, congestion with hemorrhage were observed 48 h post infection. After 3 days of anti-infective therapy in groups A, B, C, and D, lung tissue inflammation in each group gradually recovered with clear structures. The mortality rates in drug combination groups(groups C and D) were much lower than in groups A and B.   Conclusion:  The combination of minocycline with either rifampicin or amikacin is more effective against multi-drug resistant  A. baumannii  than single-agent tigecycline or polymyxin B. In addition, the mouse lung infection by ultrasonic atomization is a suitable model for drug screening and analysis of infection mechanism.

In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii