title: In vitro antimicrobial studies of silver carbene complexes: activity of free and nanoparticle carbene formulations against clinical isolates of pathogenic bacteria.
abstract: OBJECTIVE
  Silver carbenes may represent novel, broad-spectrum antimicrobial agents that have low toxicity while providing varying chemistry for targeted applications. Here, the bactericidal activity of four silver carbene complexes (SCCs) with different formulations, including nanoparticles (NPs) and micelles, was tested against a panel of clinical strains of bacteria and fungi that are the causative agents of many skin and soft tissue, respiratory, wound, blood, and nosocomial infections.
  
  
  METHODS
  MIC, MBC and multidose experiments were conducted against a broad range of bacteria and fungi. Time-release and cytotoxicity studies of the compounds were also carried out. Free SCCs and SCC NPs were tested against a panel of medically important pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter baumannii (MRAB), Pseudomonas aeruginosa, Burkholderia cepacia and Klebsiella pneumoniae.
  
  
  RESULTS
  All four SCCs demonstrated strong efficacy in concentration ranges of 0.5-90 mg/L. Clinical bacterial isolates with high inherent resistance to purified compounds were more effectively treated either with an NP formulation of these compounds or by repeated dosing. Overall, the compounds were active against highly resistant bacterial strains, such as MRSA and MRAB, and were active against the biodefence pathogens Bacillus anthracis and Yersinia pestis. All of the medically important bacterial strains tested play a role in many different infectious diseases.
  
  
  CONCLUSIONS
  The four SCCs described here, including their development as NP therapies, show great promise for treating a wide variety of bacterial and fungal pathogens that are not easily killed by routine antimicrobial agents.
authors.affiliation: Department of Biological Sciences, Northern Arizona University, PO Box 5640, Building 21, Flagstaff, AZ 86011, USA. jeff.leid@nau.edu
authors.forename: Jeff G
authors.initials: JG
authors.lastname: Leid
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ditto
authors.forename: Amanda
authors.initials: A
authors.lastname: Knapp
authors.forename: Parth N
authors.initials: PN
authors.lastname: Shah
authors.forename: Brian D
authors.initials: BD
authors.lastname: Wright
authors.forename: Robyn
authors.initials: R
authors.lastname: Blust
authors.forename: Lanette
authors.initials: L
authors.lastname: Christensen
authors.forename: C B
authors.initials: CB
authors.lastname: Clemons
authors.forename: J P
authors.initials: JP
authors.lastname: Wilber
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Young
authors.forename: Ae Gyeong
authors.initials: AG
authors.lastname: Kang
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Panzner
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Cannon
authors.forename: Yang H
authors.initials: YH
authors.lastname: Yun
authors.forename: Wiley J
authors.initials: WJ
authors.lastname: Youngs
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Seckinger
authors.forename: Emily K
authors.initials: EK
authors.lastname: Cope
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D001424:Bacterial Infections / Q000382:microbiology; D005658:Fungi / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008697:Methane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009181:Mycoses / Q000382:microbiology; D053758:Nanoparticles; D012834:Silver / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; C030011:carbene; D012834:Silver; D008697:Methane