title: In vitro efficacy of N-acetylcysteine on bacteria associated with chronic suppurative otitis media.
abstract: BACKGROUND
  The safety and efficacy of Ciprodex® has been demonstrated for treatment of chronic suppurative otitis media (CSOM). However, symptoms fail to resolve in 9-15% of patients. The objective of this study is to evaluate the efficacy of N-acetylcysteine (NAC) on S. aureus, and planktonic and sessile (biofilm forming) P. aeruginosa in vitro using clinical isolates from patients with CSOM.
  
  
  METHODS
  1) Stability was assessed using liquid chromatography-mass spectrometry for each component in a prepared mixture of Ciprodex® and NAC over 15 days. Sterility was assessed by measuring bacterial growth on a blood agar plate. Efficacy was assessed using a disc diffusion method by inoculating plates with S. aureus ATCC 29513 and P. aeruginosa ATCC 27853, and measuring the clearance zone.2) Fifteen P. aeruginosa strains were isolated from patients with CSOM and tested in vitro using the bioFILM PA™ antimicrobial susceptibility assay. Treatment solutions included Ciprodex® & ciprofloxacin +/- NAC, and NAC alone (0.25%, 0.5% & 1.25%).
  
  
  RESULTS
  1) NAC combined with Ciprodex® demonstrated stability, sterility, and efficacy over a two-week period2) P. aeruginosa strains in the sessile (33%-40%) and planktonic (13%) state demonstrated resistance to Ciprodex® and ciprofloxacin. When NAC ≥0.5% was used in isolation or as an adjunct to either of these medications, no resistance was found in the sessile or planktonic state among all 15 strains.
  
  
  CONCLUSIONS
  1) Ciprodex® combined with NAC has a shelf life of at least two weeks given the documented preservation of stability, sterility, and clinical efficacy of the mixed compounds.2) P. aeruginosa strains demonstrated resistance to both Ciprodex® and ciprofloxacin. NAC ≥0.5% overcomes issues with resistance and shows promise in the treatment of CSOM.
authors.forename: Jane
authors.initials: J
authors.lastname: Lea
authors.forename: Anne Elizabeth
authors.initials: AE
authors.lastname: Conlin
authors.forename: Inna
authors.initials: I
authors.lastname: Sekirov
authors.forename: Veronica
authors.initials: V
authors.lastname: Restelli
authors.forename: Komathi G
authors.initials: KG
authors.lastname: Ayakar
authors.forename: LeeAnn
authors.initials: L
authors.lastname: Turnbull
authors.forename: Patrick
authors.initials: P
authors.lastname: Doyle
authors.forename: Michael
authors.initials: M
authors.lastname: Noble
authors.forename: Robert
authors.initials: R
authors.lastname: Rennie
authors.forename: William E
authors.initials: WE
authors.lastname: Schreiber
authors.affiliation: Division of Otolaryngology - Head & Neck Surgery, University of British Columbia, Vancouver, BC, Canada. bwesterberg@providencehealth.bc.ca.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Westerberg
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002908:Chronic Disease; D002939:Ciprofloxacin / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D016166:Free Radical Scavengers; D006801:Humans; D066298:In Vitro Techniques; D010035:Otitis Media, Suppurative / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D016166:Free Radical Scavengers; D002939:Ciprofloxacin; D003907:Dexamethasone; D000111:Acetylcysteine