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

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.MethodsAn in vitro susceptibility test of 101 Acinetobacter baumannii was used to detect m...

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Main Authors: Songzhe eHE, Hui eHE, Yi eCHEN, Yueming eCHEN, Wei eWANG, Daojun eYU
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-05-01
Series:Frontiers in Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00507/full
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author Songzhe eHE
Hui eHE
Yi eCHEN
Yueming eCHEN
Wei eWANG
Daojun eYU
author_facet Songzhe eHE
Hui eHE
Yi eCHEN
Yueming eCHEN
Wei eWANG
Daojun eYU
author_sort Songzhe eHE
collection DOAJ
description 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.MethodsAn in vitro susceptibility test of 101 Acinetobacter baumannii was used to detect minimal inhibitory concentrations (MICs). A mouse lung infection model of multi-drug resistant Acinetobacter baumannii,established by the ultrasonic atomization method, was used to define in vivo antimicrobial activities.Results Multi-drug resistant Acinetobacter 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 24h post-infection. Lung tissue inflammation gradually increased in the model group during the first 24h after ultrasonic atomization infection; vasodilation, congestion with hemorrhage were observed 48h post infection. After three 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.ConclusionThe combination of minocycline with either rifampicin or amikacin is more effective against multidrug-resistant Acinetobacter 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.
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spelling doaj.art-173e023d35dd4ff881159d32f62801852022-12-22T01:38:38ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2015-05-01610.3389/fmicb.2015.00507136839In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumanniiSongzhe eHE0Hui eHE1Yi eCHEN2Yueming eCHEN3Wei eWANG4Daojun eYU51.The Affiliated First Hospital of Hangzhou, Zhejiang Chinese Medical University;2.Hangzhou First People’s Hospital1.The Affiliated First Hospital of Hangzhou, Zhejiang Chinese Medical University;2.Hangzhou First People’s Hospital1.The Affiliated First Hospital of Hangzhou, Zhejiang Chinese Medical University;2.Hangzhou First People’s Hospital1.The Affiliated First Hospital of Hangzhou, Zhejiang Chinese Medical University;2.Hangzhou First People’s HospitalHangzhou First People’s Hospital1.The Affiliated First Hospital of Hangzhou, Zhejiang Chinese Medical University;2.Hangzhou First People’s HospitalObjective 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.MethodsAn in vitro susceptibility test of 101 Acinetobacter baumannii was used to detect minimal inhibitory concentrations (MICs). A mouse lung infection model of multi-drug resistant Acinetobacter baumannii,established by the ultrasonic atomization method, was used to define in vivo antimicrobial activities.Results Multi-drug resistant Acinetobacter 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 24h post-infection. Lung tissue inflammation gradually increased in the model group during the first 24h after ultrasonic atomization infection; vasodilation, congestion with hemorrhage were observed 48h post infection. After three 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.ConclusionThe combination of minocycline with either rifampicin or amikacin is more effective against multidrug-resistant Acinetobacter 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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00507/fullAcinetobacter baumanniicombination treatmentUltrasonic atomizationmulti-drug resistantPneumonia infection model
spellingShingle Songzhe eHE
Hui eHE
Yi eCHEN
Yueming eCHEN
Wei eWANG
Daojun eYU
In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii
Frontiers in Microbiology
Acinetobacter baumannii
combination treatment
Ultrasonic atomization
multi-drug resistant
Pneumonia infection model
title In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii
title_full In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii
title_fullStr In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii
title_full_unstemmed In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii
title_short In vitro and in vivo analysis of antimicrobial agents alone and in combination against multi-drug resistant Acinetobacter baumannii
title_sort in vitro and in vivo analysis of antimicrobial agents alone and in combination against multi drug resistant acinetobacter baumannii
topic Acinetobacter baumannii
combination treatment
Ultrasonic atomization
multi-drug resistant
Pneumonia infection model
url http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00507/full
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