title: The use of nitric oxide releasing nanoparticles as a treatment against Acinetobacter baumannii in wound infections.
abstract: Acinetobacter baumannii (Ab) is a frequent cause of hospital acquired pneumonia and recently has increased in incidence as the causative agent of severe disease in troops wounded in Afghanistan and Iraq. Ab clinical isolates are frequently extremely resistant to antimicrobials, significantly complicating our capacity to treat infections due to this pathogen. Hence, the development of innovative therapeutics targeting mechanisms to which the bacteria are unlikely to evolve resistance is urgently needed. We examined the capacity of a nitric oxide-releasing nanoparticle (NO-np) to treat wounds infected with Ab. We found that the NO-nps were therapeutic in an experimental Ab murine wound model. Treatment with NO-nps significantly accelerated healing of infected wounds. Histological study demonstrated that NO-np treatment reduced suppurative inflammation, decreased microbial burden, and reduced the degradation of collagen. Furthermore, NO-np treatment alters the local cytokine milieu. In sum, we demonstrated that the NO-nps are an easily administered topical antimicrobial for the treatment of Ab wound infections, and our findings suggest that NO-nps may also be ideal for use in combat or disaster situations.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Mircea Radu
authors.initials: MR
authors.lastname: Mihu
authors.forename: Uriel
authors.initials: U
authors.lastname: Sandkovsky
authors.forename: George
authors.initials: G
authors.lastname: Han
authors.forename: Joel M
authors.initials: JM
authors.lastname: Friedman
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.forename: Luis R
authors.initials: LR
authors.lastname: Martinez
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003692:Delayed-Action Preparations / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D009569:Nitric Oxide / Q000627:therapeutic use*; D014946:Wound Infection / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D003692:Delayed-Action Preparations; D009569:Nitric Oxide