TY - JOUR
T1 - IB-367 pre-treatment improves the in vivo efficacy of teicoplanin and daptomycin in an animal model of wounds infected with meticillin-resistant Staphylococcus aureus
AU - Cirioni, Oscar
AU - Silvestri, Carmela
AU - Pierpaoli, Elisa
AU - Barucca, Alessandra
AU - Kamysz, Wojciech
AU - Ghiselli, Roberto
AU - Scalise, Alessandro
AU - Brescini, Lucia
AU - Castelli, Pamela
AU - Orlando, Fiorenza
AU - Kamysz, Elzbieta
AU - Guerrieri, Mario
AU - Giacometti, Andrea
AU - Provinciali, Mauro
PY - 2013
Y1 - 2013
N2 - Antimicrobial peptides are known as immunomodulators and antibiotic enhancers. We report that administration of an antimicrobial peptide, IB-367, was efficacious in increasing the antimicrobial activity of daptomycin and teicoplanin in a mouse model of wound infection caused by meticillinresistant Staphylococcus aureus (MRSA). Mice were assigned to seven groups: an IB-367 pretreated group with no antibiotics given after challenge, two IB-367 pre-treated groups plus daptomycin or teicoplanin given after challenge, two groups treated with daptomycin or teicoplanin only after challenge, and two control groups without infection or that did not receive any treatment. The main outcome measures were quantitative bacterial culture and analysis of natural killer (NK) cytotoxicity and leukocyte phenotype. The wound, established through the panniculus carnosus muscle of mice, was infected by MRSA. Bacterial cultures of mice receiving antibiotics alone showed a "2 log decrease, whilst those for IB-367 plus daptomycin or teicoplanin showed a "4 log decrease. IB-367 plus daptomycin showed the highest efficacy. The higher antimicrobial effect exerted by IB-367 was associated with increased levels of NK cytotoxicity but not of NK cell number. IB-367 increased the number of both CD11b and Gr-1 cells 3 days after MRSA challenge, whereas both of these leukocyte populations were reduced at 10 days after challenge. Our data suggest that a combination of IB-367 with antibiotic exerts a therapeutic effect and may be useful for the management of staphylococcal wounds.
AB - Antimicrobial peptides are known as immunomodulators and antibiotic enhancers. We report that administration of an antimicrobial peptide, IB-367, was efficacious in increasing the antimicrobial activity of daptomycin and teicoplanin in a mouse model of wound infection caused by meticillinresistant Staphylococcus aureus (MRSA). Mice were assigned to seven groups: an IB-367 pretreated group with no antibiotics given after challenge, two IB-367 pre-treated groups plus daptomycin or teicoplanin given after challenge, two groups treated with daptomycin or teicoplanin only after challenge, and two control groups without infection or that did not receive any treatment. The main outcome measures were quantitative bacterial culture and analysis of natural killer (NK) cytotoxicity and leukocyte phenotype. The wound, established through the panniculus carnosus muscle of mice, was infected by MRSA. Bacterial cultures of mice receiving antibiotics alone showed a "2 log decrease, whilst those for IB-367 plus daptomycin or teicoplanin showed a "4 log decrease. IB-367 plus daptomycin showed the highest efficacy. The higher antimicrobial effect exerted by IB-367 was associated with increased levels of NK cytotoxicity but not of NK cell number. IB-367 increased the number of both CD11b and Gr-1 cells 3 days after MRSA challenge, whereas both of these leukocyte populations were reduced at 10 days after challenge. Our data suggest that a combination of IB-367 with antibiotic exerts a therapeutic effect and may be useful for the management of staphylococcal wounds.
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U2 - 10.1099/jmm.0.057414-0
DO - 10.1099/jmm.0.057414-0
M3 - Article
C2 - 23813277
AN - SCOPUS:84884496607
VL - 62
SP - 1552
EP - 1558
JO - Journal of Medical Microbiology
JF - Journal of Medical Microbiology
SN - 0022-2615
IS - PART10
ER -