title: In vitro activity of MSI-78 alone and in combination with antibiotics against bacteria responsible for bloodstream infections in neutropenic patients.
abstract: MSI-78 is a 22 amino acid amphipathic peptide with potent antimicrobial activity against Gram-positive and Gram-negative organisms, including antibiotic-resistant strains. In this study, we assessed the in vitro activity of MSI-78 alone and in combination with eight clinically used antimicrobial agents against several strains of Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli isolated from blood of neutropenic febrile patients. Antimicrobial activity of MSI-78 was measured by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill studies and checkerboard titration method. The Gram-negative isolates were susceptible to the peptide at concentrations in the range 0.50-16 mg/L, while staphylococci showed lower susceptibility. MSI-78 demonstrated a higher antimicrobial activity than colistin against Gram-negative organisms. The checkerboard titration method demonstrated synergy when the peptide was combined with beta-lactams. These results provide evidence for the potential use of MSI-78 in the management of severe infections in neutropenic patients.
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy. anconacmi@interfree.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.forename: Giuseppina
authors.initials: G
authors.lastname: D'Amato
authors.forename: Carmela
authors.initials: C
authors.lastname: Silvestri
authors.forename: Alberto
authors.initials: A
authors.lastname: Licci
authors.forename: Piotr
authors.initials: P
authors.lastname: Nadolski
authors.forename: Alessandra
authors.initials: A
authors.lastname: Riva
authors.forename: Jerzy
authors.initials: J
authors.lastname: Lukasiak
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scalise
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology*; D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D003091:Colistin / Q000494:pharmacology; D015169:Colony Count, Microbial; D004359:Drug Therapy, Combination; D004926:Escherichia coli / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000150:complications; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000302:isolation & purification; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D047090:beta-Lactams; C093828:pexiganan; D003091:Colistin