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In vitro activity of imipenem-relebactam against non-MBL carbapenemase-producing Klebsiella pneumoniae isolated in Greek hospitals in 2015-2016.
Eur J Clin Microbiol Infect Dis. 2019 Jun; 38(6):1143-1150.EJ

Abstract

Relebactam is a β-lactamase inhibitor of class A and class C β-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 ≤ 2 mg/L (MIC50/90, 0.25/1 mg/L) and was considerably more active than imipenem (MIC50/90, 32/> 64 mg/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 0.25 mg/L, and from > 64 to 1 mg/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.

Authors+Show Affiliations

4th Department of Internal Medicine, Infectious Diseases Laboratory, Molecular Biology Section, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. egalani@med.uoa.gr. University General Hospital "ATTIKON", Rimini 1, 124 62, Chaidari, Greece. egalani@med.uoa.gr.4th Department of Internal Medicine, Infectious Diseases Laboratory, Molecular Biology Section, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.4th Department of Internal Medicine, Infectious Diseases Laboratory, Molecular Biology Section, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.4th Department of Internal Medicine, Infectious Diseases Laboratory, Molecular Biology Section, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.1st Internal Medicine & Infectious Diseases Clinic, Hygeia General Hospital, Marousi, Greece.1st Internal Medicine & Infectious Diseases Clinic, Hygeia General Hospital, Marousi, Greece.4th Department of Internal Medicine, Infectious Diseases Laboratory, Molecular Biology Section, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30825054

Citation

Galani, Irene, et al. "In Vitro Activity of Imipenem-relebactam Against non-MBL Carbapenemase-producing Klebsiella Pneumoniae Isolated in Greek Hospitals in 2015-2016." European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology, vol. 38, no. 6, 2019, pp. 1143-1150.
Galani I, Souli M, Nafplioti K, et al. In vitro activity of imipenem-relebactam against non-MBL carbapenemase-producing Klebsiella pneumoniae isolated in Greek hospitals in 2015-2016. Eur J Clin Microbiol Infect Dis. 2019;38(6):1143-1150.
Galani, I., Souli, M., Nafplioti, K., Adamou, P., Karaiskos, I., Giamarellou, H., & Antoniadou, A. (2019). In vitro activity of imipenem-relebactam against non-MBL carbapenemase-producing Klebsiella pneumoniae isolated in Greek hospitals in 2015-2016. European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology, 38(6), 1143-1150. https://doi.org/10.1007/s10096-019-03517-y
Galani I, et al. In Vitro Activity of Imipenem-relebactam Against non-MBL Carbapenemase-producing Klebsiella Pneumoniae Isolated in Greek Hospitals in 2015-2016. Eur J Clin Microbiol Infect Dis. 2019;38(6):1143-1150. PubMed PMID: 30825054.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro activity of imipenem-relebactam against non-MBL carbapenemase-producing Klebsiella pneumoniae isolated in Greek hospitals in 2015-2016. AU - Galani,Irene, AU - Souli,Maria, AU - Nafplioti,Konstantina, AU - Adamou,Panagiora, AU - Karaiskos,Ilias, AU - Giamarellou,Helen, AU - Antoniadou,Anastasia, AU - ,, Y1 - 2019/03/01/ PY - 2018/12/18/received PY - 2019/02/15/accepted PY - 2019/3/3/pubmed PY - 2019/9/7/medline PY - 2019/3/3/entrez KW - Carbapenemase KW - K. pneumoniae KW - KPC KW - OXA-48 KW - Relebactam SP - 1143 EP - 1150 JF - European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology JO - Eur. J. Clin. Microbiol. Infect. Dis. VL - 38 IS - 6 N2 - Relebactam is a β-lactamase inhibitor of class A and class C β-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 ≤ 2 mg/L (MIC50/90, 0.25/1 mg/L) and was considerably more active than imipenem (MIC50/90, 32/> 64 mg/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 0.25 mg/L, and from > 64 to 1 mg/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. SN - 1435-4373 UR - https://www.unboundmedicine.com/medline/citation/30825054/In_vitro_activity_of_imipenem_relebactam_against_non_MBL_carbapenemase_producing_Klebsiella_pneumoniae_isolated_in_Greek_hospitals_in_2015_2016_ L2 - https://dx.doi.org/10.1007/s10096-019-03517-y DB - PRIME DP - Unbound Medicine ER -