title: In vitro activity and in vivo animal model efficacy of IB-367 alone and in combination with imipenem and colistin against Gram-negative bacteria.
abstract: The aim of our study was to evaluate the in vitro activity of IB-367 and its bactericidal effect for Pseudomonas aeruginosa and Escherichia coli, associated to a synergic study to test the antibiotic combinations between the peptide and colistin or imipenem. Minimum inhibitory concentrations (MICs), the minimum bactericidal concentrations (MBCs), the synergy test and killing study were carried out to evaluate the IB-367 activity. In the in vivo model, a wound was incised through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 107 colony-forming units of P. aeruginosa and E. coli. For each strain, the study included an infected or not infected group that did not receive any treatment, and five contaminated groups treated with local IB- 367, intraperitoneal imipenem, intraperitoneal colistin, topical IB-367 local plus intraperitoneal imipenem or intraperitoneal colistin. All isolates were inhibited by IB-367 at concentrations of 4-64 mg/l. Killing by IB-367 was shown to be very rapid: its activity on all Gram-negative bacteria was completed within a 40 min exposure period at a concentration of 2 × MIC/l. Synergy was demonstrated when IB-367 was combined with colistin or imipenem. In in vivo studies, the groups treated with topical IB-367 and intraperitoneal colistin showed the best results in terms of bacterial load inhibition either for Pseudomonas or for E. coli. The good in vitro activity and in vivo efficacy, as well as, the synergic interactions with antibiotics suggest that IB-367 is a promising candidate for potential application in the treatment of wound Gram-negative infections.
authors: Clinic of Dermatology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy. Electronic address: o.simonetti@univpm.it.
authors: Oriana
authors: O
authors: Simonetti
authors: Clinic of Infectious Diseases, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors: Oscar
authors: O
authors: Cirioni
authors: General Surgery and Surgery Methodology Clinic, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors: Roberto
authors: R
authors: Ghiselli
authors: Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy.
authors: Fiorenza
authors: F
authors: Orlando
authors: Clinic of Infectious Diseases, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors: Carmela
authors: C
authors: Silvestri
authors: Clinic of Infectious Diseases, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors: Susanna
authors: S
authors: Mazzocato
authors: Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland.
authors: Wojciech
authors: W
authors: Kamysz
authors: Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors: Elzbieta
authors: E
authors: Kamysz
authors: Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy.
authors: Mauro
authors: M
authors: Provinciali
authors: Clinic of Infectious Diseases, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors: Andrea
authors: A
authors: Giacometti
authors: General Surgery and Surgery Methodology Clinic, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors: Mario
authors: M
authors: Guerrieri
authors: Clinic of Dermatology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors: Annamaria
authors: A
authors: Offidani
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage*; D003091:Colistin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004926:Escherichia coli / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D015378:Imipenem; C119872:antimicrobial peptide IB-367; D003091:Colistin
keywords: Animal model; Escherichia coli; IB-367; Pseudomonas aeruginosa; Wound infection