Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance

Abstract Background To evaluate the in vitro activities of plazomicin and comparator aminoglycosides and elucidate the underlying aminoglycoside resistance mechanisms among carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals. Methods Thr...

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Main Authors: Irene Galani, Konstantina Nafplioti, Panagiota Adamou, Ilias Karaiskos, Helen Giamarellou, Maria Souli, Study Collaborators
Format: Article
Language:English
Published: BMC 2019-02-01
Series:BMC Infectious Diseases
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12879-019-3801-1
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author Irene Galani
Konstantina Nafplioti
Panagiota Adamou
Ilias Karaiskos
Helen Giamarellou
Maria Souli
Study Collaborators
author_facet Irene Galani
Konstantina Nafplioti
Panagiota Adamou
Ilias Karaiskos
Helen Giamarellou
Maria Souli
Study Collaborators
author_sort Irene Galani
collection DOAJ
description Abstract Background To evaluate the in vitro activities of plazomicin and comparator aminoglycosides and elucidate the underlying aminoglycoside resistance mechanisms among carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals. Methods Three hundred single-patient carbapenemase-producing K. pneumoniae isolates were studied, including 200 KPC-, 50 NDM-, 21 VIM-, 14 KPC & VIM-, 12 OXA-48-, two NDM & OXA- and one KPC & OXA-producing isolates. Susceptibility testing was performed by broth microdilution, and minimum inhibitory concentrations (MICs) interpreted per EUCAST breakpoints. Carbapenemase-, aminoglycoside modifying enzyme- and 16S rRNA methylase- encoding genes were detected by PCR. Results Of 300 isolates tested, 5.7% were pandrug resistant and 29.3% extensively drug resistant. Plazomicin inhibited 87.0% of the isolates at ≤2 mg/L, with MIC50/MIC90 of 0.5/4 mg/L. Apramycin (a veterinary aminoglycoside) inhibited 86.7% of the isolates at ≤8 mg/L and was the second most active drug after plazomicin, followed by gentamicin (S, 43%; MIC50/MIC90, 4/> 256) and amikacin (S, 18.0%; MIC50/MIC90, 32/128). Twenty-three (7.7%) isolates (16 KPC-, 6 VIM- and one KPC & OXA-48-producers) exhibited MICs ≥64 mg/L for plazomicin, and harbored rmtB (n = 22) or armA (n = 1). AAC(6′)-Іb was the most common aminoglycoside modifying enzyme (84.7%), followed by AAC(3΄)-IIa (25.3%), while those two enzymes were co-produced by 21.4% of the isolates. Conclusions Plazomicin retains activity against most carbapenemase-producing K. pneumoniae isolated from Greek hospitals, with MICs consistently lower than those of the other aminoglycosides, even in the presence of aminoglycoside modifying enzymes. Dissemination of 16S- rRNA methylases in 8% of the isolates is an unwelcome event that needs strict infection control measures and rigorous stewardship interventions.
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spelling doaj.art-ea643aabb3024c80a2e8a2860dee1d832022-12-21T19:30:27ZengBMCBMC Infectious Diseases1471-23342019-02-0119111210.1186/s12879-019-3801-1Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistanceIrene Galani0Konstantina Nafplioti1Panagiota Adamou2Ilias Karaiskos3Helen Giamarellou4Maria Souli5Study CollaboratorsInfectious Diseases Laboratory, 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Faculty of MedicineInfectious Diseases Laboratory, 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Faculty of MedicineInfectious Diseases Laboratory, 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Faculty of Medicine6th Department of Internal Medicine, Hygeia Hospital6th Department of Internal Medicine, Hygeia HospitalInfectious Diseases Laboratory, 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Faculty of MedicineAbstract Background To evaluate the in vitro activities of plazomicin and comparator aminoglycosides and elucidate the underlying aminoglycoside resistance mechanisms among carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals. Methods Three hundred single-patient carbapenemase-producing K. pneumoniae isolates were studied, including 200 KPC-, 50 NDM-, 21 VIM-, 14 KPC & VIM-, 12 OXA-48-, two NDM & OXA- and one KPC & OXA-producing isolates. Susceptibility testing was performed by broth microdilution, and minimum inhibitory concentrations (MICs) interpreted per EUCAST breakpoints. Carbapenemase-, aminoglycoside modifying enzyme- and 16S rRNA methylase- encoding genes were detected by PCR. Results Of 300 isolates tested, 5.7% were pandrug resistant and 29.3% extensively drug resistant. Plazomicin inhibited 87.0% of the isolates at ≤2 mg/L, with MIC50/MIC90 of 0.5/4 mg/L. Apramycin (a veterinary aminoglycoside) inhibited 86.7% of the isolates at ≤8 mg/L and was the second most active drug after plazomicin, followed by gentamicin (S, 43%; MIC50/MIC90, 4/> 256) and amikacin (S, 18.0%; MIC50/MIC90, 32/128). Twenty-three (7.7%) isolates (16 KPC-, 6 VIM- and one KPC & OXA-48-producers) exhibited MICs ≥64 mg/L for plazomicin, and harbored rmtB (n = 22) or armA (n = 1). AAC(6′)-Іb was the most common aminoglycoside modifying enzyme (84.7%), followed by AAC(3΄)-IIa (25.3%), while those two enzymes were co-produced by 21.4% of the isolates. Conclusions Plazomicin retains activity against most carbapenemase-producing K. pneumoniae isolated from Greek hospitals, with MICs consistently lower than those of the other aminoglycosides, even in the presence of aminoglycoside modifying enzymes. Dissemination of 16S- rRNA methylases in 8% of the isolates is an unwelcome event that needs strict infection control measures and rigorous stewardship interventions.http://link.springer.com/article/10.1186/s12879-019-3801-1PlazomicinK. pneumoniaeCarbapenemaseGreece
spellingShingle Irene Galani
Konstantina Nafplioti
Panagiota Adamou
Ilias Karaiskos
Helen Giamarellou
Maria Souli
Study Collaborators
Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance
BMC Infectious Diseases
Plazomicin
K. pneumoniae
Carbapenemase
Greece
title Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance
title_full Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance
title_fullStr Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance
title_full_unstemmed Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance
title_short Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance
title_sort nationwide epidemiology of carbapenem resistant klebsiella pneumoniae isolates from greek hospitals with regards to plazomicin and aminoglycoside resistance
topic Plazomicin
K. pneumoniae
Carbapenemase
Greece
url http://link.springer.com/article/10.1186/s12879-019-3801-1
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