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      High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial

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          Abstract

          Objectives

          To investigate the molecular epidemiology, antimicrobial susceptibility and carbapenem resistance determinants of Acinetobacter baumannii isolates from respiratory tract samples of patients diagnosed with ventilator-associated pneumonia (VAP) who were enrolled in the MagicBullet clinical trial.

          Methods

          A. baumannii isolates were prospectively cultured from respiratory tract samples from 65 patients from 15 hospitals in Greece, Italy and Spain. Susceptibility testing was performed by broth microdilution. Carbapenem resistance determinants were identified by PCR and sequencing. Molecular epidemiology was investigated using rep-PCR (DiversiLab) and international clones (IC) were identified using our in-house database.

          Results

          Of 65 isolates, all but two isolates (97%) were resistant to imipenem and these were always associated with an acquired carbapenemase, OXA-23 (80%), OXA-40 (4.6%), OXA-58 (1.5%) or OXA-23/58 (1.5%). Resistance to colistin was 47.7%. Twenty-two isolates were XDR, and 20 isolates were pandrug-resistant (PDR). The majority of isolates clustered with IC2 ( n = 54) with one major subtype comprising isolates from 12 hospitals in the three countries, which included 19 XDR and 16 PDR isolates.

          Conclusions

          Carbapenem resistance rates were very high in A. baumannii recovered from patients with VAP. Almost half of the isolates were colistin resistant, and 42 (64.6%) isolates were XDR or PDR. Rep-PCR confirmed IC2 is the predominant clonal lineage in Europe and suggests the presence of an epidemic XDR/PDR A. baumannii clone that has spread in Greece, Italy and Spain. These data highlight the difficulty in empirical treatment of patients with A. baumannii VAP in centres with a high prevalence of carbapenem-resistant A. baumannii.

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          Most cited references26

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          Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections.

          The emergence of multidrug-resistant gram-negative bacteria and the lack of new antibiotics to combat them have led to the revival of polymyxins, an old class of cationic, cyclic polypeptide antibiotics. Polymyxin B and polymyxin E (colistin) are the 2 polymyxins used in clinical practice. Most of the reintroduction of polymyxins during the last few years is related to colistin. The polymyxins are active against selected gram-negative bacteria, including Acinetobacter species, Pseudomonas aeruginosa, Klebsiella species, and Enterobacter species. These drugs have been used extensively worldwide for decades for local use. However, parenteral use of these drugs was abandoned approximately 20 years ago in most countries, except for treatment of patients with cystic fibrosis, because of reports of common and serious nephrotoxicity and neurotoxicity. Recent studies of patients who received intravenous polymyxins for the treatment of serious P. aeruginosa and Acinetobacter baumannii infections of various types, including pneumonia, bacteremia, and urinary tract infections, have led to the conclusion that these antibiotics have acceptable effectiveness and considerably less toxicity than was reported in old studies.
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            Global spread of carbapenem-resistant Acinetobacter baumannii.

            We have investigated the molecular epidemiology and distribution of carbapenemase genes in 492 imipenem-non-susceptible Acinetobacter baumannii worldwide isolates (North and Latin America, Europe, Asia, South Africa and Australia). MICs were determined by broth microdilution and Etest. The presence of carbapenemase-encoding genes was investigated by PCR. Molecular epidemiology was performed by repetitive sequence-based PCR (rep-PCR; DiversiLab), sequence-type multiplex PCR and PFGE. Imipenem non-susceptibility was associated with ISAba1 upstream of the intrinsic bla(OXA-51-like) or the acquired carbapenemase bla(OXA-23-like), bla(OXA-40-like) or bla(OXA-58-like). Isolates were grouped into eight distinct clusters including European clones I, II and III. European clone II was the largest (246 isolates) and most widespread group (USA, pan-Europe, Israel, Asia, Australia and South Africa). The global dissemination of eight carbapenem-resistant lineages illustrates the success this organism has had in epidemic spread. The acquired OXA enzymes are widely distributed but are not the sole carbapenem resistance determinant in A. baumannii.
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              Executive Summary: Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society.

              It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
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                Author and article information

                Journal
                J Antimicrob Chemother
                J. Antimicrob. Chemother
                jac
                Journal of Antimicrobial Chemotherapy
                Oxford University Press
                0305-7453
                1460-2091
                December 2017
                08 September 2017
                08 September 2017
                : 72
                : 12
                : 3277-3282
                Affiliations
                [1 ]Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstraße 19-21, 50935 Cologne, Germany
                [2 ]German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Germany
                [3 ]Department of Clinical Microbiology and ISGlobal, Barcelona Ctr. Int. Health Res. CRESIB, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
                [4 ]Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine Infectious Diseases Research Group, Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC/University Hospital Virgen del Rocío, Seville, Spain
                Author notes
                [* ]Corresponding author. Institute for Medical Microbiology, Immunology, and Hygiene, University of Cologne, Goldenfelsstraße 19-21, 50935 Cologne, Germany. Tel: +49-221-47832011; Fax: +49-221-47832002; E-mail: paul.higgins@ 123456uni-koeln.de
                [†]

                Other members of the MagicBullet Working Group WP4 are listed in the Acknowledgements section.

                Author information
                http://orcid.org/0000-0001-8677-9454
                Article
                dkx322
                10.1093/jac/dkx322
                5890771
                28961773
                f68f553f-7bc2-4db0-bd46-f6850c89ba6e
                © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 01 June 2017
                : 20 June 2017
                : 01 August 2017
                : 01 August 2017
                Page count
                Pages: 6
                Funding
                Funded by: European Union Directorate-General
                Award ID: 278232
                Award ID: FOR2251
                Funded by: German Research Council (DFG)
                Categories
                Original Research

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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