In vitro activity of imipenem-relebactam against non-MBL carbapenemase-producing Klebsiella pneumoniae isolated in Greek hospitals in 2015-2016

被引：44

作者：

Galani, Irene ^{[1
,2
]}

Souli, Maria ^{[1
]}

Nafplioti, Konstantina ^{[1
]}

Adamou, Panagiora ^{[1
]}

Karaiskos, Ilias ^{[3
]}

Giamarellou, Helen ^{[3
]}

Antoniadou, Anastasia ^{[1
]}

Maraki, Sofia ^{[4
]}

Mavromanolaki, Viktoria Eirini ^{[4
]}

Papaioannou, Vassiliki ^{[5
]}

Tsiplakou, Sofia ^{[5
]}

Kazila, Polizo ^{[6
]}

Diamanti, Ioanna ^{[6
]}

Tsorlini, Helen ^{[7
]}

Katsifa, Helen ^{[7
]}

Charalampaki, Nikoletta ^{[8
]}

Giannopoulou, Panagiota ^{[8
]}

Trikka-Graphakos, Eleftheria ^{[8
]}

Toutouza, Marina ^{[9
]}

Vagiakou, Helen ^{[10
]}

Pappas, Konstantinos ^{[11
]}

Kyratsa, Anna ^{[12
]}

Paschali, Angeliki ^{[12
]}

Kontopoulou, Konstantina ^{[13
]}

Legga, Olga ^{[14
]}

Petinaki, Efthymia ^{[15
]}

Papadogeorgaki, Helen ^{[16
]}

Papoutsaki, Vassiliki ^{[16
]}

Chinou, Efrosini ^{[17
]}

Moraitou, Eleni ^{[18
]}

Vogiatzakis, Evangellos ^{[18
]}

Chra, Paraskevi ^{[19
]}

Baka, Vassiliki ^{[19
]}

Damala, Maria ^{[20
]}

Prifti, Eleni ^{[20
]}

机构：

[1] Natl & Kapodistrian Univ Athens, Sch Med, Mol Biol Sect, Dept Internal Med 4,Infect Dis Lab, Athens, Greece

[2] Univ Gen Hosp ATTIKON, Rimini 1, Chaidari 12462, Greece

[3] Hygeia Gen Hosp, Internal Med & Infect Dis Clin 1, Maroussi, Greece

[4] Univ Hosp Heraklion, Iraklion, Greece

[5] KAT Hosp, Athens, Greece

[6] Canc Hosp Thessaloniki THEAGENEIO, Thessaloniki, Greece

[7] G Papanikolaou Gen Hosp Thessaloniki, Thessaloniki, Greece

[8] THRIASSIO Gen Hosp, Athens, Greece

[9] Hippokrat Athens Gen Hosp, Athens, Greece

[10] Gen Hosp Athens G Gennimatas, Athens, Greece

[11] Athens Naval Hosp, Athens, Greece

[12] Gen Hosp Corfu, Corfu, Greece

[13] Gen Hosp Thessaloniki G Gennimatas, Thessaloniki, Greece

[14] Gen Hosp Lamia, Lamia, Greece

[15] Univ Hosp Larissa, Larisa, Greece

[16] Hygeia Gen Hosp, Athens, Greece

[17] St Savvas Canc Hosp, Athens, Greece

[18] Sotiria Gen & Chest Dis Hosp, Athens, Greece

[19] Korgialenio Benakio Hellen Red Cross Hosp, Athens, Greece

[20] Alexandra Gen Hosp Athens, Athens, Greece

来源：

EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES | 2019年 / 38卷 / 06期

关键词：

Relebactam; Carbapenemase; KPC; OXA-48; K; pneumoniae; CEFTAZIDIME-AVIBACTAM RESISTANCE; ENTEROBACTERIACEAE; ERTAPENEM; PORINS;

D O I：

10.1007/s10096-019-03517-y

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Relebactam is a -lactamase inhibitor of class A and class C -lactamases, including carbapenemases. We evaluated the ability of relebactam to restore imipenem susceptibility against a collection of Klebsiella pneumoniae isolates from Greek hospitals. We tested 314 non-MBL carbapenemase-producing K. pneumoniae consecutive clinical strains isolated from unique patients at 18 hospitals in Greece, between November 2014 and December 2016. Susceptibility testing of imipenem, imipenem-relebactam, meropenem, doripenem, gentamicin, and colistin was performed using broth microdilution. Additionally, MICs of ceftazidime-avibactam, fosfomycin, and tigecycline were determined by MIC Test Strips. MICs were interpreted per EUCAST breakpoints. Imipenem-relebactam MICs were interpreted using the breakpoints proposed for imipenem. Carbapenemase genes were detected using PCR. Whole genome sequencing was performed for selected isolates. Imipenem-relebactam inhibited 98.0% of the KPC-producing isolates at 2mg/L (MIC50/(90), 0.25/1mg/L) and was considerably more active than imipenem (MIC50/(90), 32/>64mg/L). Reduced activity of imipenem-relebactam was rarely detected (2%) and was associated with chromosomal factors (ompK35 disruption and/or mutated ompK36). Only ceftazidime-avibactam showed in vitro activity comparable to imipenem-relebactam (99.6% susceptible). Relebactam provided only weak potentiation of imipenem activity against K. pneumoniae with class D OXA-48-like enzymes. Relebactam exhibited strong potential for restoring the in vitro activity of imipenem against KPC-producing K. pneumoniae, lowering the imipenem MIC50 and MIC90 from 32 to 0.25mg/L, and from >64 to 1mg/L, respectively. Production of KPC carbapenemase represents the main cause of carbapenem resistance among K. pneumoniae in Greek hospitals (66.5%), and this carbapenemase appears to be very well inhibited by relebactam.

引用

页码：1143 / 1150

页数：8

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