Emergence of ceftazidime-avibactam resistance through distinct genomic adaptations in KPC-2-producing Klebsiella pneumon
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BRIEF REPORT
Emergence of ceftazidime-avibactam resistance through distinct genomic adaptations in KPC-2-producing Klebsiella pneumoniae of sequence type 39 during treatment Irene Galani 1,2 & Ilias Karaiskos 3 & Evdokia Angelidis 1 & Vassiliki Papoutsaki 3 & Lamprini Galani 3 Anastasia Antoniadou 1 & Helen Giamarellou 3
& Maria Souli
4
&
Received: 26 May 2020 / Accepted: 27 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Three ceftazidime-avibactam-resistant KPC-2-producing Klebsiella pneumoniae strains of ST39 were isolated in Greece, from rectal swabs of three patients after 10–15 days of treatment. The patients were treated with ceftazidime-avibactam as monotherapy or in combination with colistin. Two of these strains harbored a D179Y or a D179V substitution in the Ω loop of KPC-2, corresponding to KPC-33, or to the novel KPC-57, respectively. The third strain had a 15 amino acid insertion after position 259 in the KPC-2, corresponding to KPC-44. Keywords Ceftazidime-avibactam . K. pneumoniae . KPC-2 . KPC-33 . KPC-44 . KPC-57 (D179V)
In Greece, carbapenem resistance in Enterobacterales has largely been due to the plasmid-mediated Klebsiella pneumoniae carbapenemase (KPC) [1]. Ceftazidimeavibactam demonstrates activity against KPC- and OXA-48producing K. pneumoniae, but reports of ceftazidimeavibactam-resistant strains developing resistance during treatment were published soon after the launch of ceftazidimeavibactam [2]. According to the risk assessment published by the European Centre for Disease Prevention and Control (ECDC) in June 2018, the emergence of ceftazidimeElectronic supplementary material The online version of this article (https://doi.org/10.1007/s10096-020-04000-9) contains supplementary material, which is available to authorized users. * Irene Galani [email protected] 1
4th Department of Internal Medicine, Infectious Diseases Laboratory,Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece
2
University General Hospital “ATTIKON”, Rimini 1, 124 62 Chaidari, Greece
3
1st Internal Medicine & Infectious Diseases Department, Hygeia Hospital, Marousi, Greece
4
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
avibactam resistance in Europe was a very rare phenomenon but an important cross-border threat that should be monitored carefully [3]. The aim of this study was to elucidate the mechanism of ceftazidime-avibactam resistance in three KPC-producing K. pneumoniae strains isolated from surveillance cultures of three patients hospitalized in intensive care units (ICU) of a tertiary-care hospital in Athens, previously treated with ceftazidime-avibactam. Clinical data, including timeline of infection and treatment of three cases of ceftazidime-avibactam-resistant K. pneumoniae isolates emergence, are given in Online Resource 1. In all cases, patients were treated with ceftazidime-avibactam as monotherapy or in combination with colistin for a KPC-K. pneumoniae infection. Susceptibility testi
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