title: Neomycin Sulfate Improves the Antimicrobial Activity of Mupirocin-Based Antibacterial Ointments.
abstract: In the midst of the current antimicrobial pipeline void, alternative approaches are needed to reduce the incidence of infection and decrease reliance on last-resort antibiotics for the therapeutic intervention of bacterial pathogens. In that regard, mupirocin ointment-based decolonization and wound maintenance practices have proven effective in reducing Staphylococcus aureus transmission and mitigating invasive disease. However, the emergence of mupirocin-resistant strains has compromised the agent's efficacy, necessitating new strategies for the prevention of staphylococcal infections. Herein, we set out to improve the performance of mupirocin-based ointments. A screen of a Food and Drug Administration (FDA)-approved drug library revealed that the antibiotic neomycin sulfate potentiates the antimicrobial activity of mupirocin, whereas other library antibiotics did not. Preliminary mechanism of action studies indicate that neomycin's potentiating activity may be mediated by inhibition of the organism's RNase P function, an enzyme that is believed to participate in the tRNA processing pathway immediately upstream of the primary target of mupirocin. The improved antimicrobial activity of neomycin and mupirocin was maintained in ointment formulations and reduced S. aureus bacterial burden in murine models of nasal colonization and wound site infections. Combination therapy improved upon the effects of either agent alone and was effective in the treatment of contemporary methicillin-susceptible, methicillin-resistant, and high-level mupirocin-resistant S. aureus strains. From these perspectives, combination mupirocin-and-neomycin ointments appear to be superior to that of mupirocin alone and warrant further development.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Catlyn
authors.initials: C
authors.lastname: Blanchard
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Brooks
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Beckley
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Colquhoun
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA paul_dunman@urmc.rochester.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Dunman
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002353:Carrier State / Q000188:drug therapy / Q000517:prevention & control; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D005260:Female; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D016712:Mupirocin / Q000627:therapeutic use*; D009296:Nasal Cavity / Q000382:microbiology; D009355:Neomycin / Q000627:therapeutic use*; D009824:Ointments / Q000627:therapeutic use; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D043262:Ribonuclease P / Q000037:antagonists & inhibitors; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000517:prevention & control; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D009824:Ointments; D012336:RNA, Ribosomal, 16S; D016712:Mupirocin; D043262:Ribonuclease P; D009355:Neomycin