title: Vitamin E improves the in vivo efficacy of tigecycline and daptomycin in an animal model of wounds infected with meticillin-resistant Staphylococcus aureus.
abstract: A relevant bacterial load in cutaneous wounds significantly interferes with the normal process of healing. Vitamin E (VE) is a known immunomodulator and immune enhancer. Here, it was shown that administration of VE before infection was effective at increasing the antimicrobial activity of daptomycin (DAP) or tigecycline (TIG) in a mouse model of wound infection caused by meticillin-resistant Staphylococcus aureus (MRSA). A wound was established through the panniculus carnosus of mice and inoculated with MRSA. Mice were assigned to six groups: a VE pre-treated group with no antibiotics given after MRSA challenge; two VE pre-treated groups with DAP or TIG given after MRSA challenge; two groups treated with DAP or TIG only after MRSA challenge; and a control group that did not receive any treatment. Mice receiving each antibiotic alone showed a 3 log decrease in the number of c.f.u. recovered compared with the control group, mice treated with VE plus TIG had a 4 log decrease, whilst mice treated with VE plus DAP had the largest decrease in c.f.u. recovered (5 logs). The increased antimicrobial effect seen from treatment with VE plus antibiotics was associated with increased levels of natural killer cell cytotoxicity, with a more pronounced increase in leukocyte populations in mice treated with VE plus DAP. These data suggest that treatment with VE prior to infection and subsequent antibiotic treatment act in synergy.
authors.affiliation: Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA-IRCCS, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Provinciali
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.affiliation: Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA-IRCCS, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.affiliation: Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA-IRCCS, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pierpaoli
authors.affiliation: Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA-IRCCS, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Barucca
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Silvestri
authors.affiliation: General Surgery and Surgery Methodology Clinic, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ghiselli
authors.affiliation: Department of Plastic and Reconstructive Surgery General Surgery, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scalise
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Brescini
authors.affiliation: General Surgery and Surgery Methodology Clinic, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Guerrieri
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017576:Daptomycin / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D056747:Immunomodulation / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D000078304:Tigecycline; D014810:Vitamin E / Q000494:pharmacology* / Q000627:therapeutic use; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D014810:Vitamin E; D000078304:Tigecycline; D008911:Minocycline; D017576:Daptomycin