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      The Acinetobacter baumannii Oxymoron: Commensal Hospital Dweller Turned Pan-Drug-Resistant Menace

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          Abstract

          During the past few decades Acinetobacter baumannii has evolved from being a commensal dweller of health-care facilities to constitute one of the most annoying pathogens responsible for hospitalary outbreaks and it is currently considered one of the most important nosocomial pathogens. In a prevalence study of infections in intensive care units conducted among 75 countries of the five continents, this microorganism was found to be the fifth most common pathogen. Two main features contribute to the success of A. baumannii: (i) A. baumannii exhibits an outstanding ability to accumulate a great variety of resistance mechanisms acquired by different mechanisms, either mutations or acquisition of genetic elements such as plasmids, integrons, transposons, or resistant islands, making this microorganism multi- or pan-drug-resistant and (ii) The ability to survive in the environment during prolonged periods of time which, combined with its innate resistance to desiccation and disinfectants, makes A. baumannii almost impossible to eradicate from the clinical setting. In addition, its ability to produce biofilm greatly contributes to both persistence and resistance. In this review, the pathogenesis of the infections caused by this microorganism as well as the molecular bases of antibacterial resistance and clinical aspects such as treatment and potential future therapeutic strategies are discussed in depth.

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          Carbapenemases: the versatile beta-lactamases.

          Carbapenemases are beta-lactamases with versatile hydrolytic capacities. They have the ability to hydrolyze penicillins, cephalosporins, monobactams, and carbapenems. Bacteria producing these beta-lactamases may cause serious infections in which the carbapenemase activity renders many beta-lactams ineffective. Carbapenemases are members of the molecular class A, B, and D beta-lactamases. Class A and D enzymes have a serine-based hydrolytic mechanism, while class B enzymes are metallo-beta-lactamases that contain zinc in the active site. The class A carbapenemase group includes members of the SME, IMI, NMC, GES, and KPC families. Of these, the KPC carbapenemases are the most prevalent, found mostly on plasmids in Klebsiella pneumoniae. The class D carbapenemases consist of OXA-type beta-lactamases frequently detected in Acinetobacter baumannii. The metallo-beta-lactamases belong to the IMP, VIM, SPM, GIM, and SIM families and have been detected primarily in Pseudomonas aeruginosa; however, there are increasing numbers of reports worldwide of this group of beta-lactamases in the Enterobacteriaceae. This review updates the characteristics, epidemiology, and detection of the carbapenemases found in pathogenic bacteria.
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            Drugs for bad bugs: confronting the challenges of antibacterial discovery.

            The sequencing of the first complete bacterial genome in 1995 heralded a new era of hope for antibacterial drug discoverers, who now had the tools to search entire genomes for new antibacterial targets. Several companies, including GlaxoSmithKline, moved back into the antibacterials area and embraced a genomics-derived, target-based approach to screen for new classes of drugs with novel modes of action. Here, we share our experience of evaluating more than 300 genes and 70 high-throughput screening campaigns over a period of 7 years, and look at what we learned and how that has influenced GlaxoSmithKline's antibacterials strategy going forward.
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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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                Author and article information

                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbio.
                Frontiers in Microbiology
                Frontiers Research Foundation
                1664-302X
                29 January 2012
                23 April 2012
                2012
                : 3
                : 148
                Affiliations
                [1] 1simpleDepartment of Clinical Microbiology, School of Medicine, IDIBAPS and Barcelona Centre for International Health Research, Hospital Clínic-Universitat de Barcelona Barcelona, Spain
                Author notes

                Edited by: Stefania Stefani, University of Catania, Italy

                Reviewed by: Ilda Santos Sanches, Universidade nova de Lisboa, Portugal; Paolo Visca, University Roma Tre, Italy

                *Correspondence: Jordi Vila, Department of Clinical Microbiology, Hospital Clinic of Barcelona, Villarroel, 170, 08036 Barcelona, Spain. e-mail: jvila@ 123456ub.edu

                This article was submitted to Frontiers in Antimicrobials, Resistance and Chemotherapy, a specialty of Frontiers in Microbiology.

                Article
                10.3389/fmicb.2012.00148
                3333477
                22536199
                fea88a16-d645-4b19-99d1-54e826482d11
                Copyright © 2012 Roca, Espinal, Vila-Farrés and Vila.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

                History
                : 11 November 2011
                : 28 March 2012
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 356, Pages: 30, Words: 30692
                Categories
                Microbiology
                Review Article

                Microbiology & Virology
                acinetobacter baumannii,biofilm,antimicrobial resistance,pathogenesis,antimicrobial peptides

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