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Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains

The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1–11, was evaluat... Full description

Journal Title: European journal of clinical microbiology & infectious diseases 2017-05-03, Vol.36 (10), p.1739-1748
Main Author: Morici, P
Other Authors: Florio, W , Rizzato, C , Ghelardi, E , Tavanti, A , Rossolini, G. M , Lupetti, A
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0934-9723
Link: https://www.ncbi.nlm.nih.gov/pubmed/28470337
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recordid: cdi_proquest_miscellaneous_1895278306
title: Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains
format: Article
creator:
  • Morici, P
  • Florio, W
  • Rizzato, C
  • Ghelardi, E
  • Tavanti, A
  • Rossolini, G. M
  • Lupetti, A
subjects:
  • Aminoglycosides
  • Anti-Bacterial Agents - pharmacology
  • Antibacterial activity
  • Antibacterial agents
  • Antibiotics
  • Antimicrobial agents
  • Bacteria
  • Bacterial pneumonia
  • Bacterial Proteins - genetics
  • Bactericidal activity
  • Beta lactamases
  • beta-Lactamases - genetics
  • Biomedical and Life Sciences
  • Biomedicine
  • Carbapenem-Resistant Enterobacteriaceae - drug effects
  • Carbapenem-Resistant Enterobacteriaceae - enzymology
  • Carbapenem-Resistant Enterobacteriaceae - genetics
  • Carbapenemase
  • Clarithromycin
  • Clindamycin
  • Colistin
  • Drug resistance
  • Drug resistance in microorganisms
  • Drug Synergism
  • Gentamicin
  • Gram-negative bacteria
  • Health aspects
  • Humans
  • Hydrophobicity
  • Internal Medicine
  • Klebsiella
  • Klebsiella pneumoniae - drug effects
  • Klebsiella pneumoniae - enzymology
  • Klebsiella pneumoniae - genetics
  • Lactoferrin
  • Lactoferrin - genetics
  • Lactoferrin - pharmacology
  • Lactoferrins
  • Medical Microbiology
  • Microbial Sensitivity Tests
  • Multidrug resistance
  • Original Article
  • Peptides
  • Peptides - genetics
  • Peptides - pharmacology
  • Pneumonia
  • Rifampin
  • Sensitizing
  • Strains (organisms)
  • Synergistic effect
  • Tigecycline
  • Titration
ispartof: European journal of clinical microbiology & infectious diseases, 2017-05-03, Vol.36 (10), p.1739-1748
description: The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1–11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1–11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1–11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1–11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1–11 and colistin are not strictly associated, and suggest an hLF1–11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1–11 in combination with antibiotics is a promising candidate to treat infections caused by MDR- K. pneumoniae strains.
language: eng
source:
identifier: ISSN: 0934-9723
fulltext: no_fulltext
issn:
  • 0934-9723
  • 1435-4373
url: Link


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titleSynergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains
creatorMorici, P ; Florio, W ; Rizzato, C ; Ghelardi, E ; Tavanti, A ; Rossolini, G. M ; Lupetti, A
creatorcontribMorici, P ; Florio, W ; Rizzato, C ; Ghelardi, E ; Tavanti, A ; Rossolini, G. M ; Lupetti, A
descriptionThe spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1–11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1–11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1–11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1–11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1–11 and colistin are not strictly associated, and suggest an hLF1–11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1–11 in combination with antibiotics is a promising candidate to treat infections caused by MDR- K. pneumoniae strains.
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1EISSN: 1435-4373
2DOI: 10.1007/s10096-017-2987-7
3PMID: 28470337
languageeng
publisherBerlin/Heidelberg: Springer Berlin Heidelberg
subjectAminoglycosides ; Anti-Bacterial Agents - pharmacology ; Antibacterial activity ; Antibacterial agents ; Antibiotics ; Antimicrobial agents ; Bacteria ; Bacterial pneumonia ; Bacterial Proteins - genetics ; Bactericidal activity ; Beta lactamases ; beta-Lactamases - genetics ; Biomedical and Life Sciences ; Biomedicine ; Carbapenem-Resistant Enterobacteriaceae - drug effects ; Carbapenem-Resistant Enterobacteriaceae - enzymology ; Carbapenem-Resistant Enterobacteriaceae - genetics ; Carbapenemase ; Clarithromycin ; Clindamycin ; Colistin ; Drug resistance ; Drug resistance in microorganisms ; Drug Synergism ; Gentamicin ; Gram-negative bacteria ; Health aspects ; Humans ; Hydrophobicity ; Internal Medicine ; Klebsiella ; Klebsiella pneumoniae - drug effects ; Klebsiella pneumoniae - enzymology ; Klebsiella pneumoniae - genetics ; Lactoferrin ; Lactoferrin - genetics ; Lactoferrin - pharmacology ; Lactoferrins ; Medical Microbiology ; Microbial Sensitivity Tests ; Multidrug resistance ; Original Article ; Peptides ; Peptides - genetics ; Peptides - pharmacology ; Pneumonia ; Rifampin ; Sensitizing ; Strains (organisms) ; Synergistic effect ; Tigecycline ; Titration
ispartofEuropean journal of clinical microbiology & infectious diseases, 2017-05-03, Vol.36 (10), p.1739-1748
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0Springer-Verlag Berlin Heidelberg 2017
1COPYRIGHT 2017 Springer
2European Journal of Clinical Microbiology & Infectious Diseases is a copyright of Springer, 2017.
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3Ghelardi, E
4Tavanti, A
5Rossolini, G. M
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0Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains
1European journal of clinical microbiology & infectious diseases
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descriptionThe spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1–11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1–11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1–11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1–11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1–11 and colistin are not strictly associated, and suggest an hLF1–11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1–11 in combination with antibiotics is a promising candidate to treat infections caused by MDR- K. pneumoniae strains.
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0Aminoglycosides
1Anti-Bacterial Agents - pharmacology
2Antibacterial activity
3Antibacterial agents
4Antibiotics
5Antimicrobial agents
6Bacteria
7Bacterial pneumonia
8Bacterial Proteins - genetics
9Bactericidal activity
10Beta lactamases
11beta-Lactamases - genetics
12Biomedical and Life Sciences
13Biomedicine
14Carbapenem-Resistant Enterobacteriaceae - drug effects
15Carbapenem-Resistant Enterobacteriaceae - enzymology
16Carbapenem-Resistant Enterobacteriaceae - genetics
17Carbapenemase
18Clarithromycin
19Clindamycin
20Colistin
21Drug resistance
22Drug resistance in microorganisms
23Drug Synergism
24Gentamicin
25Gram-negative bacteria
26Health aspects
27Humans
28Hydrophobicity
29Internal Medicine
30Klebsiella
31Klebsiella pneumoniae - drug effects
32Klebsiella pneumoniae - enzymology
33Klebsiella pneumoniae - genetics
34Lactoferrin
35Lactoferrin - genetics
36Lactoferrin - pharmacology
37Lactoferrins
38Medical Microbiology
39Microbial Sensitivity Tests
40Multidrug resistance
41Original Article
42Peptides
43Peptides - genetics
44Peptides - pharmacology
45Pneumonia
46Rifampin
47Sensitizing
48Strains (organisms)
49Synergistic effect
50Tigecycline
51Titration
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titleSynergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains
authorMorici, P ; Florio, W ; Rizzato, C ; Ghelardi, E ; Tavanti, A ; Rossolini, G. M ; Lupetti, A
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0Aminoglycosides
1Anti-Bacterial Agents - pharmacology
2Antibacterial activity
3Antibacterial agents
4Antibiotics
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6Bacteria
7Bacterial pneumonia
8Bacterial Proteins - genetics
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10Beta lactamases
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46Rifampin
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abstractThe spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1–11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1–11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1–11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1–11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1–11 and colistin are not strictly associated, and suggest an hLF1–11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1–11 in combination with antibiotics is a promising candidate to treat infections caused by MDR- K. pneumoniae strains.
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pubSpringer Berlin Heidelberg
pmid28470337
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