title: Interaction of chlorhexidine with trisEDTA or miconazole in vitro against canine meticillin-resistant and -susceptible Staphylococcus pseudintermedius isolates from two UK regions.
abstract: BACKGROUND
  Topical therapy is an important alternative to systemic antibacterial therapy for treatment of canine superficial pyoderma in light of the emergence of multidrug-resistant staphylococci. Chlorhexidine is widely used in shampoo products alone or in combination with miconazole or tromethamine-ethylenediaminetetraacetic acid (trisEDTA). Comparisons of these combinations have not been made.
  
  
  OBJECTIVE
  To determine minimum inhibitory concentrations (MICs) of combinations of chlorhexidine/miconazole and chlorhexidine/trisEDTA in vitro in a collection of Staphylococcus pseudintermedius (SP) from northern (NUK) and southeastern (SEUK) United Kingdom (UK) sources.
  
  
  METHODS
  MICs of chlorhexidine, miconazole, trisEDTA and combinations of chlorhexidine/miconazole (1:1) or chlorhexidine/trisEDTA (80:16:1 and 80:5:1) were determined for 196 canine SP isolates from NUK [49 meticillin-resistant (MRSP), 50 meticillin-susceptible (MSSP)] and fom SEUK (48 MRSP, 49 MSSP) using agar dilution.
  
  
  RESULTS
  TrisEDTA alone did not inhibit growth. Chlorhexidine/miconazole MICs (median = 0.5 mg/L) were lower than those of either drug alone (P < 0.05) and lower than chlorhexidine/trisEDTA MICs (median = 1 mg/L; P < 0.0005) in each bacterial type and from both regions, except for miconazole in NUK MSSP. An additive interaction was noted between chlorhexidine and miconazole or trisEDTA (80:16:1 ratio) in 79 and 43 isolates, respectively, whereas antagonism between chlorhexidine and trisEDTA was noted for three isolates. NUK isolates were more susceptible than SEUK isolates (P < 0.05), except MRSP exposed to chlorhexidine and the chlorhexidine/trisEDTA (80:16:1) combination.
  
  
  CONCLUSIONS
  These low MICs are likely to be exceeded by topical therapy. Evaluation of the mechanisms by which chlorhexidine combinations interact to reduce MICs is warranted, in view of increasing concerns of biocide tolerance in staphylococci.
authors.affiliation: Department of Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, UK. sclark@rvc.ac.uk.
authors.forename: Siân-Marie
authors.initials: SM
authors.lastname: Clark
authors.affiliation: Department of Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, UK.
authors.forename: Anette
authors.initials: A
authors.lastname: Loeffler
authors.affiliation: School of Veterinary Science, University of Liverpool, Chester High Road, Neston, CH64 7TE, UK.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Schmidt
authors.affiliation: Department of Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, UK.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Chang
authors.affiliation: Department of Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Wilson
authors.affiliation: School of Veterinary Science, University of Liverpool, Chester High Road, Neston, CH64 7TE, UK.
authors.forename: Dorina
authors.initials: D
authors.lastname: Timofte
authors.affiliation: Department of Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, UK.
authors.forename: Ross
authors.initials: R
authors.lastname: Bond
mesh_terms: D000818:Animals; D002710:Chlorhexidine / Q000008:administration & dosage / Q000494:pharmacology*; D004283:Dog Diseases / Q000453:epidemiology / Q000382:microbiology*; D004285:Dogs; D004347:Drug Interactions; D004492:Edetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance; D008825:Miconazole / Q000008:administration & dosage / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013207:Staphylococcal Skin Infections / Q000453:epidemiology / Q000382:microbiology / Q000662:veterinary*; D013210:Staphylococcus / Q000145:classification / Q000187:drug effects; D014325:Tromethamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D014325:Tromethamine; D008825:Miconazole; D004492:Edetic Acid; D008712:Methicillin; D002710:Chlorhexidine