Efficacy of pexiganan combination with tigecycline in a mouse model of Pseudomonas aeruginosa sepsis

Oscar Cirioni , Oriana Simonetti , Gianluca Morroni , Lucia Brescini , Wojciech Kamysz , Elżbieta Kamysz , Fiorenza Orlando , Elisa Pierpaoli , Miriam Caffarini , Monia Orciani , Claudio Agostinelli , Annamaria Offidani , Mauro Provinciali , Andrea Giacometti

Abstract

Background: Pseudomonas aeruginosa is a gram-negative pathogen, related with a severe mortality rate. It is also difficult to treat due to numerous resistance mechanisms to a wide range of antibiotics. Objective: Evaluate the activity of pexiganan, an antimicrobial peptide, in combination with two clinical antibiotics (azithromycin and tigecycline) that are not active against P. aeruginosa. Method: Ten clinical P. aeruginosa were isolated from urinary tract infections, blood culture, skin infections and respiratory tract infections. Minimum inhibitory concentrations (MICs) and synergies were evaluated by broth microdilution, checkerboard assays and time-kill studies. In vitro synergy was confirmed with an in vivo experiment using a murine model of sepsis. Results: Pexiganan MICs were included between 2 and 16 mg/L. Tigecycline and azithromycin MICs were high as expected (4-64 mg/L and 32-256 mg/L, respectively). Pexiganan and azithromycin combination resulted to be additive or indifferent while tigecycline and pexiganan combination were synergic against seven out of ten P. aeruginosa and additive against the other strains. In vivo experiment confirmed the in vitro synergy, denoting a significative reduction of bacteria in mice treated with pexiganan and tigecycline combination. Conclusions: Antimicrobial peptides are molecules that could be useful in the fight against infections and pexiganan seems to be one of the most promising. Our results demonstrated that, in association with tigecycline, pexiganan administration could overcome antibiotic resistance and increase the effectiveness of treatment against P. aeruginosa sepsis.
Author Oscar Cirioni
Oscar Cirioni,,
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, Oriana Simonetti
Oriana Simonetti,,
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, Gianluca Morroni
Gianluca Morroni,,
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, Lucia Brescini
Lucia Brescini,,
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, Wojciech Kamysz
Wojciech Kamysz,,
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, Elżbieta Kamysz (FCh / DMBt / LChBM)
Elżbieta Kamysz,,
- Laboratory of Chemistry of Biological Macromolecules
, Fiorenza Orlando
Fiorenza Orlando,,
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, Elisa Pierpaoli
Elisa Pierpaoli,,
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, Miriam Caffarini
Miriam Caffarini,,
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, Monia Orciani
Monia Orciani,,
-
et al.`
Journal seriesCurrent Topics in Medicinal Chemistry, ISSN 1568-0266, e-ISSN 1873-4294, (A 40 pkt)
Issue year2018
Vol18
No24
Pages2127-2132
Publication size in sheets0.5
Keywords in EnglishPseudomonas aeruginosa, pexiganan, tigecycline, azithromycin, antibiotic combinations, murine sepsis model
ASJC Classification2700 General Medicine; 3002 Drug Discovery
DOIDOI:10.2174/1568026619666181219123431
Languageen angielski
Score (nominal)40
Score sourcejournalList
ScoreMinisterial score = 40.0, 04-04-2020, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 0.866; WoS Impact Factor: 2018 = 3.442 (2) - 2018=3.144 (5)
Citation count*1 (2020-05-21)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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