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      Cure of recurring Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae septic shock episodes due to complicated soft tissue infection using a ceftazidime and avibactam-based regimen: a case report

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          Abstract

          Background

          Infections caused by multidrug-resistant Enterobacteriaceae are hard to treat and life-threatening due to reduced therapeutic options. Systemic infections caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae strains have increased in many European regions, becoming frequent in many clinical settings, and are associated with high mortality. The co-formulation of ceftazidime, a third-generation cephalosporin, with avibactam, a new suicide inhibitor beta-lactamase inhibitor able to block most Klebsiella pneumoniae carbapenemases, has been recently licensed, with promising results in patients with limited or absent therapeutic options. Little is known, however, as to the efficacy of such a combination in patients with soft tissue infections caused by multidrug-resistant Klebsiella pneumoniae carbapenemase-producing strains of Klebsiella pneumoniae.

          Case presentation

          A Caucasian 53-year-old man with paraplegia suffered multiple vertebral fractures due to a car crash. He was treated with external fixators that became infected early after insertion and were repeatedly and inefficiently treated with multiple antibiotics. He suffered repeated septic episodes caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae strains with a multidrug-resistant profile. Meropenem, tigecycline, and colistin combinations allowed only temporary improvements, but septic shock episodes recurred, in spite of removal of infected external fixators. After approval of pre-marketing prescription by our local Ethics Committee, full clinical resolution was obtained with a compassionate treatment using meropenem and ceftazidime/avibactam in combination for 16 days.

          Conclusions

          Our experience provides additional evidence that ceftazidime/avibactam, possibly in combination with meropenem rescued by avibactam, may be an efficacious treatment option also for complicated skin and soft tissue infections caused by multidrug-resistant strains of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae.

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          Most cited references8

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          Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia.

          There are no data comparing outcomes of patients treated with ceftazidime-avibactam versus comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, ceftazidime-avibactam treatment of carbapenem-resistant Klebsiella pneumoniae bacteremia was associated with higher rates of clinical success (P = 0.006) and survival (P = 0.01) than other regimens. Across treatment groups, there were no differences in underlying diseases, severity of illness, source of bacteremia, or strain characteristics (97% produced K. pneumoniae carbapenemase). Aminoglycoside- and colistin-containing regimens were associated with increased rates of nephrotoxicity (P = 0.002).
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            First Report of Ceftazidime-Avibactam Resistance in a KPC-3-Expressing Klebsiella pneumoniae Isolate.

            Ceftazidime-avibactam is the first antimicrobial approved by the U.S. FDA for the treatment of carbapenem-resistant Enterobacteriaceae. Avibactam, a non-β-lactam β-lactamase inhibitor, inactivates class A serine carbapenemases, including Klebsiella pneumoniae carbapenemase (KPC). We report a KPC-producing K. pneumoniae isolate resistant to ceftazidime-avibactam (MIC, 32/4 μg/ml) from a patient with no prior treatment with ceftazidime-avibactam.
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              Ceftazidime-Avibactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination for the Treatment of Resistant Gram-negative Organisms.

              Multidrug-resistant gram-negative bacterial infections have emerged as a major threat in hospitalized patients. Treatment options are often inadequate and, as a result, these infections are associated with high mortality. A cephalosporin and a novel synthetic non-β-lactam, β-lactamase inhibitor, ceftazidime-avibactam, is approved for the treatment of serious infections caused by resistant gram-negative bacteria. This article reviews the spectrum of activity, clinical pharmacology, pharmacodynamic and pharmacokinetic properties, clinical efficacy and tolerability, and dosing and administration of ceftazidime-avibactam.
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                Author and article information

                Contributors
                +390854252410 , parruti@tin.it
                antofrattari@gmail.com
                e.polilli@libero.it
                vincenzosavini@yahoo.it
                antonina.sciacca@ausl.pe.it
                augusta.consorte@gmail.com
                donatellacibelli@yahoo.it
                adriana.agostinone@ausl.pe.it
                francesco.dimasi@ausl.pe.it
                alessandro.pieri@ausl.pe.it
                pierluigi.cacciatore@ausl.pe.it
                giancarlo.diiorio@ausl.pe.it
                paolo.fazii@tin.it
                tullio.spina@ausl.pe.it
                Journal
                J Med Case Rep
                J Med Case Rep
                Journal of Medical Case Reports
                BioMed Central (London )
                1752-1947
                22 January 2019
                22 January 2019
                2019
                : 13
                : 20
                Affiliations
                [1 ]GRID grid.461844.b, Infectious Diseases Unit, , Pescara General Hospital, ; Via Fonte Romana 8, 65124 Pescara, Italy
                [2 ]GRID grid.461844.b, Anaesthesia and Intensive Care Unit, , Pescara General Hospital, ; Pescara, Italy
                [3 ]GRID grid.461844.b, Clinical Pathology Unit, , Pescara General Hospital, ; Pescara, Italy
                [4 ]GRID grid.461844.b, Microbiology and Virology Unit, , Pescara General Hospital, ; Pescara, Italy
                Article
                1934
                10.1186/s13256-018-1934-2
                6341597
                30665450
                04e344e7-b69b-41e1-aba6-baa4db369afd
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 January 2018
                : 25 November 2018
                Categories
                Case Report
                Custom metadata
                © The Author(s) 2019

                Medicine
                sepsis,klebsiella pneumoniae carbapenemase (kpc)-producing klebsiella pneumoniae,treatment

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