Inactivation of mgrB gene regulator and resistance to colistin is becoming endemic in carbapenem-resistant Klebsiella pneumoniae in Greece: A nationwide study from 2014 to 2017

Mouna Hamel (1, 2) , Stylianos Chatzipanagiotou (3) , Linda Hadjadj (1, 2) , Efthimia Petinaki (4) , Sophia Papagianni , Nikoletta Charalampaki , Sophia Tsiplakou , Vassiliki Papaioannou , Nikoletta Skarmoutsou , Iris Spiliopoulou , Myrto Christofidou , Nikolaos Papamichalopoulos (3) , Tilemachos Skalidis (5) , Nicholaos Legakis (5) , Kimon Fountoulis (5) , Efstathia Perivolioti (6) , Heleni Kraniotaki (6) , Maria Bournia (6) , Anastasios Ioannidis (3) , Alexandra Baron Sophie (1, 2) , Jean-Marc Rolain (1, 2)

1 MEPHI - Microbes évolution phylogénie et infections
2 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
3 NKUA - National and Kapodistrian University of Athens
4 University Hospital of Larissa
5 "IASO" General Hospital of Athens
6 Evangelismos Athens General Hospital

Introduction: In Greece, the spread of carbapenem-resistant Enterobacteriaceae in humans has led to the reintroduction of colistin as a therapeutic agent. Unfortunately, colistin resistance with different mechanisms has emerged. The present work aims to determine the prevalence of carbapenem and colistin resistance and the corresponding mechanisms in Klebsiella pneumoniae clinical isolates from Greece. Methods: From 2014 to 2017, 288 carbapenem-resistant K. pneumoniae clinical strains were gathered from a collection of 973 isolates from eight different hospitals in Greece. Antibiotic susceptibility testing was performed using three different methods. Screening of carbapenem and colistin resistance genes was conducted using polymerase chain reaction (PCR) amplification and sequencing. Results: Among the 288 (29.6 %) carbapenem-resistant isolates, 213 (73.9%) were colistin-resistant (minimum inhibitory concentration [MIC] >2 mg/L). The KPC type was the most common carbapenemase gene (116; 40.3%), followed by VIM (41; 14.2%), NDM (33; 11.5%) and OXA-48 (22; 7.6%). Moreover, 44 (15.3%) strains co-produced two types of carbapenemases. No mcr genes were detected for colistin resistance but mutations in chromosomal genes were found. These included inactivation of the mgrB gene for 148 (69.5%) strains, including insertion sequences for 94 (44.1%), nonsense mutations for 4 (1.9%) and missense mutations for 24 (11.3%). Moreover, PCR amplification of mgrB gene was negative for 26 (12.2%) strains. Finally, 65 (30.5%) colistin-resistant strains exhibited a wild-type mgrB, the mechanisms of which remain to be elucidated. Conclusion: This study shows that K. pneumoniae clinical strains in Greece are resistant to both carbapenems and colistin and this is endemic and is likely chromosomally encoded. (C) 2020 Published by Elsevier B.V.

Domaines: Sciences du Vivant [q-bio]

Mouna Hamel, Stylianos Chatzipanagiotou, Linda Hadjadj, Efthimia Petinaki, Sophia Papagianni, et al.. Inactivation of mgrB gene regulator and resistance to colistin is becoming endemic in carbapenem-resistant Klebsiella pneumoniae in Greece: A nationwide study from 2014 to 2017. International Journal of Antimicrobial Agents, 2020, 55 (4), ⟨10.1016/j.ijantimicag.2020.105930⟩. ⟨hal-03150172⟩