Identification of AbaR4 #Acinetobacter baumannii #resistance island in clinical isolates of blaOXA-23-positive #Proteus mirabilis (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Identification of AbaR4 Acinetobacter baumannii resistance island in clinical isolates of blaOXA-23-positive Proteus mirabilis

Sophie Octavia, Weizhen Xu, Oon Tek Ng, Kalisvar Marimuthu, Indumathi Venkatachalam, Bernadette Cheng, Raymond T P Lin, Jeanette W P Teo

Journal of Antimicrobial Chemotherapy, dkz472, https://doi.org/10.1093/jac/dkz472

Published: 14 November 2019

 

Abstract

Objectives

blaOXA-23 is a class D carbapenemase-encoding gene typical of the Acinetobacter genus. However, its occurrence in the Enterobacteriaceae is uncommon. Here we provide the genome characterization of blaOXA-23-positive Proteus mirabilis.

Methods

In Singapore, a national surveillance of carbapenem non-susceptible clinical Enterobacteriaceae has enabled the collection of OXA-23 bearing isolates. Three clinical P. mirabilis were whole-genome sequenced using Oxford Nanopore MinION and Illumina platforms. The sequence accuracy of MinION long-read contigs was enhanced by polishing with Illumina-derived short-read data.

Results

In two P. mirabilis genomes, blaOXA-23 was detected as two copies, present on the chromosome and on a 60 018 bp plasmid. blaOXA-23 was associated with the classic Acinetobacter composite transposon Tn2006, bounded by two copies of ISAba1 bracketing the carbapenemase gene. The Tn2006 itself was embedded within an Acinetobacter baumannii AbaR4 resistance island. In the chromosome, the AbaR4 was found integrated into the comM gene, which is also the preferred ‘hotspot’ in A. baumannii. In the plasmid, AbaR4 integrated into a putative colicin gene.

Conclusions

Our description of an A. baumannii AbaR4 encoding blaOXA-23 in P. mirabilis is to our knowledge the first description of an Acinetobacter resistance island in Proteus and suggests that P. mirabilis may be a reservoir for this class D carbapenemase gene.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Acinetobacter baumannii; Proteus mirabilis; Singapore.

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Characterization of #phenotypic and #genotypic traits of #carbapenem-resistant #Acinetobacter baumannii clinical isolates recovered from a tertiary care #hospital in #Taif, #Saudi Arabia (Infect Drug Resist., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Infect Drug Resist. 2019 Oct 3;12:3113-3124. doi: 10.2147/IDR.S206691. eCollection 2019.

Characterization of phenotypic and genotypic traits of carbapenem-resistant Acinetobacter baumannii clinical isolates recovered from a tertiary care hospital in Taif, Saudi Arabia.

El-Badawy MF1,2, Abdelwahab SF1,3, Alghamdi SA4, Shohayeb MM1,5.

Author information: 1 Division of Pharmaceutical Microbiology, Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, Taif 21974, Kingdom of Saudi Arabia. 2 Department of Microbiology and Immunology, Faculty of Pharmacy, Misr University for Science and Technology, 6th of October City 12568, Egypt. 3 Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia 61511, Egypt. 4 Medical Genetics, Clinical Laboratory Department, College of Applied Medical Sciences, Taif University, Taif 21974, Kingdom of Saudi Arabia. 5 Department of Microbiology and Biotechnology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 35712, Egypt.

 

Abstract

BACKGROUND AND OBJECTIVE:

Acinetobacter baumannii (A. baumannii) is a common nosocomial pathogen, which developed multi-drug-resistance to different classes of antibiotics including carbapenems. This study examined ten common carbapenemase genes among 32 carbapenem-resistant A. baumannii clinical isolates recovered from Taif, Saudi Arabia.

METHODS:

Isolates were phenotypically identified to the genus level by Vitek®2 and API 20NE®. The species level was confirmed by the amplification of bla OXA-51. The susceptibility for 21 different antibiotics was performed by Vitek 2 and modified Kirby-Bauer method. Isolates were genetically screened for 10 carbapenemases. Phylogenetic relatedness between isolates was determined by ERIC-PCR.

RESULTS:

Genotypically identified A. baumannii represented 100% of the total phenotypically identified Acinetobacter spp. All the carbapenem-resistant isolates were sensitive to polymyxin B and colistin. Among the other antibiotics, ampicillin/sulbactam and tigecycline were the most effective agents. 90.8% of the isolates were resistant to all ten investigated β-lactams. bla OXA-51, bla IPM, bla NDM and bla OXA-23 were detected in 100%, 87.5%, 62.5% and 59.4% of isolates, respectively. Also, bla VIM and bla OXA-40 were less prevalent and were detected in 9.3% and 3.1% of the isolates, respectively. In addition, bla KPC, bla OXA-48, bla OXA-58, bla OXA-181 were not detected in any isolate. The A. baumannii isolates were categorised into ten genotypes on the basis of the detected carbapenemase genes and ERIC-PCR revealed a remarkable clonal diversity among these isolates.

CONCLUSION:

Class A and class D carbapenemase genes were the most commonly detected among carbapenem resistant A. baumannii (CRAB) clinical isolates.

© 2019 El-Badawy et al.

KEYWORDS: A. baumannii; ERIC-PCR; blaOXA-51; carbapenemases; carbapenems

PMID: 31632100 PMCID: PMC6781848 DOI: 10.2147/IDR.S206691

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Acinetobacter baumannii; Nosocomial outbreaks; Saudi Arabia.

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A novel #plasmid-encoded #mcr-4.3 gene in a #colistin-resistant #Acinetobacter baumannii clinical strain (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

A novel plasmid-encoded mcr-4.3 gene in a colistin-resistant Acinetobacter baumannii clinical strain

Natacha Martins-Sorenson, Erik Snesrud, Danilo Elias Xavier, Luciana Camila Cacci, Anthony T Iavarone, Patrick McGann, Lee W Riley, Beatriz Meurer Moreira

Journal of Antimicrobial Chemotherapy, dkz413, https://doi.org/10.1093/jac/dkz413

Published: 03 October 2019

 

Abstract

Objectives

To identify the molecular mechanism of colistin resistance in an MDR Acinetobacter baumannii clinical strain isolated in 2008 from a meningitis case in Brazil.

Methods

Long- and short-read WGS was used to identify colistin resistance genes in A. baumannii strain 597A with a colistin MIC of 64 mg/L. MS was used to analyse lipid A content. mcr was cloned into pET-26b (+) and transformed into Escherichia coli BL21(λDE3)pLysS for analysis.

Results

A novel plasmid (pAb-MCR4.3) harbouring mcr-4.3 within a Tn3-like transposon was identified. The A. baumannii 597A lipid A MS spectra showed a main molecular ion peak at m/z = 2034, which indicated the addition of phosphoethanolamine to the lipid A structure. E. coli BL21 transformed with pET-26b-mcr-4.3 gained colistin resistance with a colistin MIC of 8 mg/L.

Conclusions

Colistin resistance in A. baumannii 597A was correlated with the presence of a novel plasmid-encoded mcr-4.3 gene.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; MCR4; Colistin; Acinetobacter baumannii; Brazil.

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#Control and #Elimination of #XDR #Acinetobacter baumanii in an #ICU (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 10—October 2019 / Dispatch

Control and Elimination of Extensively Drug-Resistant Acinetobacter baumanii in an Intensive Care Unit

Amanda Chamieh1, Tania Dagher Nawfal1, Tala Ballouz1, Claude Afif, George Juvelekian, Sani Hlais, Jean-Marc Rolain, and Eid Azar

Author affiliations: University of Balamand, Beirut, Lebanon (A. Chamieh, T. Ballouz, C. Afif, G. Juvelekian, E. Azar); Aix-Marseille University, Marseille, France (T.D. Nawfal, J.-M. Rolain); Saint Joseph University and American University of Beirut, Beirut (S. Hlais)

 

Abstract

We decreased antimicrobial drug consumption in an intensive care unit in Lebanon by changing to colistin monotherapy for extensively drug-resistant Acinetobacter baumanii infections. We saw a 78% decrease of A. baumanii in sputum and near-elimination of blaoxa-23-carrying sequence type 2 clone over the 1-year study. Non–A. baumanii multidrug-resistant infections remained stable.

Keywords: Antibiotics; Drugs Resistance; Colistin; Acinetobacter baumannii; Lebanon; ICU.

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In Vitro Activity of #Minocycline against #US Isolates of #Acinetobacter baumannii – Acinetobacter calcoaceticus species complex, …: Results from the SENTRY Antimicrobial Surveillance Program (2014-2018) (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

In Vitro Activity of Minocycline against U.S. Isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus species complex, Stenotrophomonas maltophilia, and Burkholderia cepacia complex: Results from the SENTRY Antimicrobial Surveillance Program (2014-2018)

Robert K. Flamm, Dee Shortridge, Mariana Castanheira, Helio S. Sader, Michael A. Pfaller

DOI: 10.1128/AAC.01154-19

 

ABSTRACT

We evaluated the activity of minocycline and comparator agents against a large number of Stenotrophomonas maltophilia (n = 1,289), Acinetobacter baumannii-Acinetobacter calcoaceticus species complex (n = 1,081), and Burkholderia cepacia complex (n = 101) collected during 2014 through 2018 from 87 U.S. medical centers spanning all nine census divisions. The isolates were collected primarily from hospitalized patients with pneumonia (1,632 isolates; 66.0% overall), skin and skin structure infections (354 isolates; 14.3% overall), bloodstream infections (266 isolates; 10.8% overall), urinary tract infections (126 isolates; 5.1% overall), intra-abdominal infections (61 isolates; 2.5% overall), and other infections (32 isolates; 1.3% overall). Against A. baumannii-A. calcoaceticus species complex, colistin was the most active agent exhibiting MIC50/90 values at ≤0.5/2 μg/ml and 92.4% susceptible. Minocycline ranked second in activity with MIC50/90 values at 0.25/8 μg/ml and susceptibility at 85.7%. Activity for these two agents was reduced against extensively drug-resistant and multidrug-resistant isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus species complex. Only two agents showed high levels of activity (susceptibility >90%) against S. maltophilia: minocycline (MIC50/90, 0.5/2 μg/ml; 99.5% susceptible) and trimethoprim-sulfamethoxazole (MIC50/90, ≤0.5/1 μg/ml; 94.6% susceptible). Minocycline was active against 92.8% (MIC90, 4 μg/ml) of trimethoprim-sulfamethoxazole-resistant S. maltophilia isolates. Various agents exhibited susceptibility rates of nearly 90% against B. cepacia complex: trimethoprim-sulfamethoxazole (MIC50/90, ≤0.5/2 μg/ml; 93.1% susceptible), ceftazidime (MIC50/90, 2/8 μg/ml; 91.0%), meropenem (MIC50/90, 2/8 μg/ml; 89.1%) and minocycline (MIC50/90, 2/8 μg/ml; 88.1% susceptible). These results indicate that minocycline is among the most active agents for these three problematic potential pathogen groups when tested against U.S. isolates.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Minocycline; Colistin; Acinetobacter baumannii; Burkholderia cepacia; USA.

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#Factors associated with #fatality due to #avian #influenza A(#H7N9) #infection in #China (Clin Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Clin Infect Dis. 2019 Aug 16. pii: ciz779. doi: 10.1093/cid/ciz779. [Epub ahead of print]

Factors associated with fatality due to avian influenza A(H7N9) infection in China.

Zheng S1,2,3, Zou Q2,3, Wang X2,3, Bao J2,3, Yu F2,3, Guo F4, Liu P5, Shen Y6, Wang Y7, Yang S1, Wu W1, Sheng J1, Vijaykrishna D8,9, Gao H1,4, Chen Y1,2,3.

Author information: 1 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P.R. China. 2 Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, P.R. China. 3 Center of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P.R. China. 4 Department of Infectious Diseases, Shulan (Hangzhou) Hospital, Hangzhou, P.R. China. 5 Department of Infectious Diseases, The second hospital of Ningbo, Ningbo, P.R. China. 6 Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, P.R. China. 7 Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, Beijing, P.R. China. 8 Department of Microbiology, Biomedicine Discovery Institute, Monash University, Victoria, Australia. 9 World Health Organization Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

 

Abstract

BACKGROUND:

The high case fatality rate of influenza A H7N9 infected patients has been a major clinical concern.

METHODS:

To identify the common causes of death due to H7N9 as well as identify risk factors associated with the high inpatient mortality, we retrospectively collected clinical treatment information from 350 hospitalized human cases of H7N9 virus in mainland China during 2013-2017, of which 109 (31.1%) had died, and systematically analysed the patient’s clinical characteristics and risk factors for death.

RESULTS:

The median age of infection was 57 years, whereas the median age of mortality was 61 years, significantly older than those survived. In contrast to previous studies, we found nosocomial infections, comprising Acinetobacter baumannii and Klebsiella most commonly associated with secondary bacterial infections, which was likely due to the high utilization of supportive therapies, including mechanical ventilation (52.6%), ECMO (14%), CRRT (19.1%), and artificial liver therapy (9.7%). Age, time from illness onset to antiviral therapy initiation and secondary bacterial infection were independent risk factors for death. Age >65, secondary bacterial infections, and initiation of neuraminidase inhibitors therapy after 5 days from symptom onset were associated with increased risk of death.

CONCLUSIONS:

Fatality among H7N9 virus infected patients occurred rapidly after hospital admission, especially among older patients, and was followed by severe hypoxemia and multisystem organ failure. Our results show that early neuraminidase-inhibitor therapy and reduction of secondary bacterial infections can help reduce mortality.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

KEYWORDS: H7N9; Influenza; Risk factors; zoonotic infection

PMID: 31418813 DOI: 10.1093/cid/ciz779

Keywords: Antivirals; Antibiotics; Avian Influenza; H7N9; Human; China; Klebsiella pneumoniae; Acinetobacter baumannii.

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#Therapeutic efficacy of LN-1-255 in combination with #imipenem in severe #infection caused by #carbapenem-resistant #Acinetobacter baumannii (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Therapeutic efficacy of LN-1-255 in combination with imipenem in severe infection caused by carbapenem-resistant Acinetobacter baumannii

Juan Carlos Vázquez-Ucha, Marta Martínez-Guitián, María Maneiro, Kelly Conde-Pérez, Laura Álvarez-Fraga, Gabriel Torrens, Antonio Oliver, John D. Buynak, Robert A. Bonomo,Germán Bou, Concepción González-Bello, Margarita Poza, Alejandro Beceiro

DOI: 10.1128/AAC.01092-19

 

ABSTRACT

OBJETIVES:

The Carbapenem-Hydrolyzing Class D β-Lactamases (CHDLs) are the main mechanism of carbapenem resistance in A. baumannii. CHDLs are not effectively inactivated by clinically available β-lactam-type inhibitors. We have previously described the in vitroefficacy of the inhibitor LN-1-255 in combination with carbapenems. The aim of this study was to compare the efficacy of LN-1-255 with that of imipenem in murine pneumonia using A. baumannii strains carrying their most extended carbapenemases: OXA-23 and OXA-24/40.

METHODS:

The blaOXA-23 and blaOXA-24/40 genes were cloned into carbapenem-susceptible A. baumannii ATCC 17978 strain. Clinical isolates AB1 and JC12/04, producing the enzymes OXA-23 and OXA-24/40, respectively, were used in the study. Pharmacokinetic parameters were determined. An experimental pneumonia model was used to evaluate the efficacy of the combined imipenem/LN-1-255 therapy.

RESULTS:

MICs of imipenem decreased between 32 and 128-fold in presence of LN-1-255. Intramuscular treatment with imipenem/LN-1-255 (30/50 mg/Kg) decreased the bacterial burden i) 4 and 1.7 log10 CFU/g lung in the infection with the ATCC 17978-OXA-23 and the AB1 strains, respectively and ii) 2.5 and 4.5 log10 CFU/g lung the infection produced by the ATCC 17978-OXA-24/40 and the JC12/04 strains, respectively. In all assays combined therapy offered higher protection against pneumonia than those treated with monoteraphy. No toxicity was observed in treated mice.

CONCLUSIONS:

Imipenem treatment combined with LN-1-255 reduced significantly the severity of infection by carbapenem-resistant A. baumannii strains carrying CHDLs. Preclinical assays demonstrated the potential of the therapy of LN-1-255 and imipenem as new antibacterial treatment.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Imipenem; Acinetobacter baumannii; Animal models.

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