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

Songzhe He,Hui He,Yi Chen,Wei Wang,Daojun Yu,Yueming Chen

doi:10.3389/fmicb.2015.00507

Abstract

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.

Highlights

Acinetobacter baumannii is a nonfermentative, gram-negative bacillus, whose natural reservoir still remains to be determined
In vitro Antibacterial Activity of Antimicrobial Agents Alone The 101 multi-resistant strains tested in this study were completely resistant to piperacillin/tazobactam sodium, ceftazidime, levofloxacin, amikacin, fosfomycin sodium, chloramphenicol (Resistance rate: 100%), and had high resistance to imipenem/cilastatin sodium, cefoperazone/sulbactam, erythromycin (Resistance rate: >79%)
In vitro Antibacterial Activity of Antimicrobial Agents in Combination Chloramphenicol had no additive effects in combination with other antimicrobial agents, with the exception of polymyxin B

Summary

Introduction

Acinetobacter baumannii is a nonfermentative, gram-negative bacillus, whose natural reservoir still remains to be determined. It can represent an opportunistic pathogen in humans, and Antibiotics against MDR A. baumannii often causes nosocomial infections in immunocompromised patients, such as pneumonia, urinary tract infection, and sepsis (Dettori et al, 2014). Most studies on A. baumannii have focused on antibiotic resistance, treatment and epidemiological analysis (Erac et al, 2014). With the large amount of clinical applications of antibiotics, the isolation rate of drug-resistant A. baumannii has been gradually rising, and the emergence of multi-drug resistant strains poses a big challenge for antibiotic treatment (Lee et al, 2011; Sievert et al, 2013).

Methods

Results

Conclusion