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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.

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          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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          Author and article information

          Journal
          Eur. J. Clin. Microbiol. Infect. Dis.
          European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
          Springer Nature
          1435-4373
          0934-9723
          May 03 2017
          Affiliations
          [1 ] Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, Via San Zeno 37, 56127, Pisa, Italy.
          [2 ] NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, Pisa, Italy.
          [3 ] Department of Biology, University of Pisa, Via San Zeno 37, 56127, Pisa, Italy.
          [4 ] Department of Medical Biotechnologies, University of Siena, Siena, Italy.
          [5 ] Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy.
          [6 ] Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
          [7 ] Don Carlo Gnocchi Foundation, Florence, Italy.
          [8 ] Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, Via San Zeno 37, 56127, Pisa, Italy. antonella.lupetti@med.unipi.it.
          Article
          10.1007/s10096-017-2987-7
          10.1007/s10096-017-2987-7
          28470337
          d6d22674-90d4-46b1-ad03-44d976e4251f
          History

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