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European Journal of Clinical Microbiology & Infectious Diseases

Published in:

01-10-2017 | Original Article

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

Authors: P. Morici, W. Florio, C. Rizzato, E. Ghelardi, A. Tavanti, G. M. Rossolini, A. Lupetti

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 10/2017

Abstract

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.

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Title: Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains
Authors: P. Morici
W. Florio
C. Rizzato
E. Ghelardi
A. Tavanti
G. M. Rossolini
A. Lupetti
Publication date: 01-10-2017
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Clinical Microbiology & Infectious Diseases / Issue 10/2017
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI: https://doi.org/10.1007/s10096-017-2987-7

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