In vitro and in vivo Activity of Combinations of Polymyxin B with Other Antimicrobials Against Carbapenem-Resistant Acinetobacter baumannii

Hui Zhang,1 Yunzhu Zhu,1 Ning Yang,1 Qinxiang Kong,2 Yahong Zheng,1 Na Lv,1 Haoran Chen,1 Chengcheng Yue,1 Yanyan Liu,1,3,4 Jiabin Li,1– 4 Ying Ye1 1Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of I...

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Autores principales:	Zhang H, Zhu Y, Yang N, Kong Q, Zheng Y, Lv N, Chen H, Yue C, Liu Y, Li J, Ye Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	acinetobacter baumannii carbapenem-resistant pneumonia infection model polymyxin b combination treatment Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/9ffa1688c0ef4dab82f4c49656391800
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spelling	oai:doaj.org-article:9ffa1688c0ef4dab82f4c496563918002021-11-07T18:42:56ZIn vitro and in vivo Activity of Combinations of Polymyxin B with Other Antimicrobials Against Carbapenem-Resistant Acinetobacter baumannii1178-6973https://doaj.org/article/9ffa1688c0ef4dab82f4c496563918002021-11-01T00:00:00Zhttps://www.dovepress.com/in-vitro-and-in-vivo-activity-of-combinations-of-polymyxin-b-with-othe-peer-reviewed-fulltext-article-IDRhttps://doaj.org/toc/1178-6973Hui Zhang,1 Yunzhu Zhu,1 Ning Yang,1 Qinxiang Kong,2 Yahong Zheng,1 Na Lv,1 Haoran Chen,1 Chengcheng Yue,1 Yanyan Liu,1,3,4 Jiabin Li,1– 4 Ying Ye1 1Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Infectious Diseases, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, People’s Republic of China; 4Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Ying Ye; Jiabin LiDepartment of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Jixi Road no. 218, Hefei, Anhui, People’s Republic of ChinaTel +86-551-62922713Fax +86-551-62922281Email yeying2@139.com; lijiabin@ahmu.edu.cnPurpose: To study the in vitro and in vivo antibacterial activities of polymyxin B (PB) and other five antimicrobial agents, including imipenem (IMP), meropenem (MEM), tigecycline (TGC), sulbactam (SUL), and rifampicin (RIF), alone or in combination against carbapenem-resistant Acinetobacter baumannii (CRAB).Methods: Microbroth dilution method was used to determine the minimum inhibitory concentration (MIC) of ten strains of CRAB against six antibacterial drugs, and the checkerboard method was used to determine the fractional inhibitory concentration index (FICI). A mouse pneumonia model was established by intranasal instillation of Ab5075 to evaluate the antibacterial activity in vivo.Results: The resistance rate of ten CRAB strains to IMP, MEM, and SUL was 100%, that to PB and TGC was 0%, and that to RIF was 20%. When PB was used in combination with the other five antibiotics in vitro, it mainly showed synergistic and additive effects on CRAB. The synergistic effect of PB and RIF was maximal, followed by MEM and IMP but was weak with SUL and TGC. In vivo, compared to the model group (untreated with antibiotics), treatment group (six antibiotics alone and PB combined with the other five antibiotics) reduced the bacterial load in the lung tissue and the serum inflammatory factors (IL-1β, IL-6, and TNF-α). The bacterial load and the inflammatory factors of the combined group decreased significantly than that of the single group (P< 0.05). The IL-6 and TNF-α values of the PB combined with the RIF group were significantly lower than the two drugs used individually.Conclusion: The combination of PB and IMP, MEM, and RIF exerted robust in vitro synergistic effects on CRAB isolates. The combination of PB and the other five antimicrobial agents had a better effect in the mouse pneumonia model than single agent, while the combination of PB and RIF had the best effect.Keywords: Acinetobacter baumannii, carbapenem-resistant, pneumonia infection model, polymyxin B, combination treatmentZhang HZhu YYang NKong QZheng YLv NChen HYue CLiu YLi JYe YDove Medical Pressarticleacinetobacter baumanniicarbapenem-resistantpneumonia infection modelpolymyxin bcombination treatmentInfectious and parasitic diseasesRC109-216ENInfection and Drug Resistance, Vol Volume 14, Pp 4657-4666 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acinetobacter baumannii carbapenem-resistant pneumonia infection model polymyxin b combination treatment Infectious and parasitic diseases RC109-216
spellingShingle	acinetobacter baumannii carbapenem-resistant pneumonia infection model polymyxin b combination treatment Infectious and parasitic diseases RC109-216 Zhang H Zhu Y Yang N Kong Q Zheng Y Lv N Chen H Yue C Liu Y Li J Ye Y In vitro and in vivo Activity of Combinations of Polymyxin B with Other Antimicrobials Against Carbapenem-Resistant Acinetobacter baumannii
description	Hui Zhang,1 Yunzhu Zhu,1 Ning Yang,1 Qinxiang Kong,2 Yahong Zheng,1 Na Lv,1 Haoran Chen,1 Chengcheng Yue,1 Yanyan Liu,1,3,4 Jiabin Li,1– 4 Ying Ye1 1Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Infectious Diseases, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, People’s Republic of China; 4Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Ying Ye; Jiabin LiDepartment of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Jixi Road no. 218, Hefei, Anhui, People’s Republic of ChinaTel +86-551-62922713Fax +86-551-62922281Email yeying2@139.com; lijiabin@ahmu.edu.cnPurpose: To study the in vitro and in vivo antibacterial activities of polymyxin B (PB) and other five antimicrobial agents, including imipenem (IMP), meropenem (MEM), tigecycline (TGC), sulbactam (SUL), and rifampicin (RIF), alone or in combination against carbapenem-resistant Acinetobacter baumannii (CRAB).Methods: Microbroth dilution method was used to determine the minimum inhibitory concentration (MIC) of ten strains of CRAB against six antibacterial drugs, and the checkerboard method was used to determine the fractional inhibitory concentration index (FICI). A mouse pneumonia model was established by intranasal instillation of Ab5075 to evaluate the antibacterial activity in vivo.Results: The resistance rate of ten CRAB strains to IMP, MEM, and SUL was 100%, that to PB and TGC was 0%, and that to RIF was 20%. When PB was used in combination with the other five antibiotics in vitro, it mainly showed synergistic and additive effects on CRAB. The synergistic effect of PB and RIF was maximal, followed by MEM and IMP but was weak with SUL and TGC. In vivo, compared to the model group (untreated with antibiotics), treatment group (six antibiotics alone and PB combined with the other five antibiotics) reduced the bacterial load in the lung tissue and the serum inflammatory factors (IL-1β, IL-6, and TNF-α). The bacterial load and the inflammatory factors of the combined group decreased significantly than that of the single group (P< 0.05). The IL-6 and TNF-α values of the PB combined with the RIF group were significantly lower than the two drugs used individually.Conclusion: The combination of PB and IMP, MEM, and RIF exerted robust in vitro synergistic effects on CRAB isolates. The combination of PB and the other five antimicrobial agents had a better effect in the mouse pneumonia model than single agent, while the combination of PB and RIF had the best effect.Keywords: Acinetobacter baumannii, carbapenem-resistant, pneumonia infection model, polymyxin B, combination treatment
format	article
author	Zhang H Zhu Y Yang N Kong Q Zheng Y Lv N Chen H Yue C Liu Y Li J Ye Y
author_facet	Zhang H Zhu Y Yang N Kong Q Zheng Y Lv N Chen H Yue C Liu Y Li J Ye Y
author_sort	Zhang H
title	In vitro and in vivo Activity of Combinations of Polymyxin B with Other Antimicrobials Against Carbapenem-Resistant Acinetobacter baumannii
title_short	In vitro and in vivo Activity of Combinations of Polymyxin B with Other Antimicrobials Against Carbapenem-Resistant Acinetobacter baumannii
title_full	In vitro and in vivo Activity of Combinations of Polymyxin B with Other Antimicrobials Against Carbapenem-Resistant Acinetobacter baumannii
title_fullStr	In vitro and in vivo Activity of Combinations of Polymyxin B with Other Antimicrobials Against Carbapenem-Resistant Acinetobacter baumannii
title_full_unstemmed	In vitro and in vivo Activity of Combinations of Polymyxin B with Other Antimicrobials Against Carbapenem-Resistant Acinetobacter baumannii
title_sort	in vitro and in vivo activity of combinations of polymyxin b with other antimicrobials against carbapenem-resistant acinetobacter baumannii
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/9ffa1688c0ef4dab82f4c49656391800
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In vitro and in vivo Activity of Combinations of Polymyxin B with Other Antimicrobials Against Carbapenem-Resistant Acinetobacter baumannii

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