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Analysis of global prevalence of antibiotic resistance in Acinetobacter baumannii infections disclosed a faster increase in OECD countries.

ABSTRACT: Acinetobacter baumannii is one of the most challenging nosocomial pathogens due to the emergence and widespread of antibiotic resistance. We aimed to provide the first analysis of global prevalence of antibiotic resistance in A. baumannii infections, by synthesizing data and knowledge through a systematic review. We searched studies reporting antibiotic resistance in A. baumannii infections using the Medline, Embase, Web of Science, and Cochrane databases from January 2000 to December 2016. Studies were eligible if they investigated and reported antibiotic resistance in A. baumannii infections with inpatients or outpatients in hospital. Our investigation showed a high prevalence of resistance to the common prescribed antibiotics in A. baumannii infections in both OECD (Organization for Economic Co-operation and Development) and non-OECD countries. Strikingly, though OECD countries have substantially lower pooled prevalence of resistance compared to non-OECD countries based on the data during 2006-2016, a further investigation in a time scale disclosed a faster increase in OECD countries during the past 11 years, and currently both of them have a comparable prevalence of resistance (2011-2016). Tigecycline and colistin are still active but their resistances are expected to become common if the preventative measures are not taken. Antibiotic resistance in A. baumannii infection developed fast and is a crisis for both OECD and non-OECD countries. A "post-antibiotic era" for A. baumannii infection is expected in the next 10-20 years without immediate actions from pharmaceutical companies and governments.

SUBMITTER: Xie R

PROVIDER: S-EPMC5849731 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Analysis of global prevalence of antibiotic resistance in Acinetobacter baumannii infections disclosed a faster increase in OECD countries.

Xie Ruiqiang R Zhang Xiaohua Douglas XD Zhao Qi Q Peng Bo B Zheng Jun J

Emerging microbes & infections 20180314 1

Acinetobacter baumannii is one of the most challenging nosocomial pathogens due to the emergence and widespread of antibiotic resistance. We aimed to provide the first analysis of global prevalence of antibiotic resistance in A. baumannii infections, by synthesizing data and knowledge through a systematic review. We searched studies reporting antibiotic resistance in A. baumannii infections using the Medline, Embase, Web of Science, and Cochrane databases from January 2000 to December 2016. Stud ...[more]

PMID: 29535298

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Project description:Global challenges presented by multidrug-resistant Acinetobacter baumannii infections have stimulated the development of new treatment strategies. We reported that outer membrane protein W (OmpW) is a potential therapeutic target in A. baumannii. Here, a library of 11,648 natural compounds was subjected to a primary screening using quantitative structure-activity relationship (QSAR) models generated from a ChEMBL data set with >7,000 compounds with their reported minimal inhibitory concentration (MIC) values against A. baumannii followed by a structure-based virtual screening against OmpW. In silico pharmacokinetic evaluation was conducted to assess the drug-likeness of these compounds. The ten highest-ranking compounds were found to bind with an energy score ranging from -7.8 to -7.0 kcal/mol where most of them belonged to curcuminoids. To validate these findings, one lead compound exhibiting promising binding stability as well as favorable pharmacokinetics properties, namely demethoxycurcumin, was tested against a panel of A. baumannii strains to determine its antibacterial activity using microdilution and time-kill curve assays. To validate whether the compound binds to the selected target, an OmpW-deficient mutant was studied and compared with the wild type. Our results demonstrate that demethoxycurcumin in monotherapy and in combination with colistin is active against all A. baumannii strains. Finally, the compound was found to significantly reduce the A. baumannii interaction with host cells, suggesting its anti-virulence properties. Collectively, this study demonstrates machine learning as a promising strategy for the discovery of curcuminoids as antimicrobial agents for combating A. baumannii infections.ImportanceAcinetobacter baumannii presents a severe global health threat, with alarming levels of antimicrobial resistance rates resulting in significant morbidity and mortality in the USA, ranging from 26% to 68%, as reported by the Centers for Disease Control and Prevention (CDC). To address this threat, novel strategies beyond traditional antibiotics are imperative. Computational approaches, such as QSAR models leverage molecular structures to predict biological effects, expediting drug discovery. We identified OmpW as a potential therapeutic target in A. baumannii and screened 11,648 natural compounds. We employed QSAR models from a ChEMBL bioactivity data set and conducted structure-based virtual screening against OmpW. Demethoxycurcumin, a lead compound, exhibited promising antibacterial activity against A. baumannii, including multidrug-resistant strains. Additionally, demethoxycurcumin demonstrated anti-virulence properties by reducing A. baumannii interaction with host cells. The findings highlight the potential of artificial intelligence in discovering curcuminoids as effective antimicrobial agents against A. baumannii infections, offering a promising strategy to address antibiotic resistance.

Dataset Information

Analysis of global prevalence of antibiotic resistance in Acinetobacter baumannii infections disclosed a faster increase in OECD countries.

Publications

Analysis of global prevalence of antibiotic resistance in Acinetobacter baumannii infections disclosed a faster increase in OECD countries.

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