title: In vitroeffectiveness of triterpenoids and their synergistic effect with antibiotics againstStaphylococcus aureusstrains.
abstract: OBJECTIVE
  The aim of this study is to evaluate the effect of four triterpenoids such as oleanolic acid, ursolic acid, cycloastragenol, and beta-boswellic acid alone and in combination with antibiotics againstStaphylococcus aureusstrains.
  
  
  METHODS
  Sixteen clinical strains ofS. aureusfrom infected wounds were isolated. Eight were methicillin-sensitiveS. aureus(MSSA), and the other eight were methicillin-resistantS. aureus(MRSA). The activity was also seen in referenceS. aureusAmerican Type Culture Collection™strains. The activity of all the triterpenoids and antibiotics againstS. aureuswas evaluated by broth microdilution method. The effectiveness was judged by comparing the minimum inhibitory concentrations (MICs) of the compounds with antibiotics. The combination of antibiotics with compounds was evaluated by their fractional inhibitory concentrations (FIC).
  
  
  RESULTS
  Against both clinical and reference MSSA strains, none of the compounds exhibited comparable activity to antibiotics vancomycin or cefradine except for ursolic acid (MIC 7.8 μg/ml). Against MRSA, all compounds (MIC 16-128 μg/ml) showed lesser activity than vancomycin (MIC 5.8 μg/ml). Among triterpenoid-antibiotic combinations, the most effective were ursolic acid and vancomycin against clinical strain MSSA (FICS0.17). However, overall, different combinations between triterpenoids and antibiotics showed 95%-46% (P< 0.05) reduction in MICs of antibiotics compared to when antibiotics were used alone. Cefradine, a drug not suitable for treating MRSA (MIC = 45 μg/ml), showed a remarkable decrease in its MIC (87% P< 0.01) when it was used in combination with oleanolic acid or ursolic acid in both clinical and reference strains.
  
  
  CONCLUSIONS
  The tested triterpenoids are relatively weaker than antibiotics. However, when used in combination with antibiotics, they showed remarkable synergistic effect and thus can help in prolonging the viability of these antibiotics againstS. aureusinfections. Furthermore, reduction in MIC of cefradine with oleanolic acid indicates their potential use against MRSA.
authors.affiliation: Department of Surgery, Rawalpindi Medical College, Rawalpindi, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hamza
authors.affiliation: Department of Surgery, Rawalpindi Medical College, Rawalpindi, Pakistan.
authors.forename: Maha
authors.initials: M
authors.lastname: Nadir
authors.affiliation: Department of Surgery, Rawalpindi Medical College, Rawalpindi, Pakistan.
authors.forename: Nadir
authors.initials: N
authors.lastname: Mehmood
authors.affiliation: Department of Science, National Institute of Science and Technical Education, Islamabad, Pakistan.
authors.forename: Adeel
authors.initials: A
authors.lastname: Farooq
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D009828:Oleanolic Acid / Q000008:administration & dosage*; D012502:Sapogenins / Q000008:administration & dosage*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D014315:Triterpenes / Q000008:administration & dosage*; D000097245:Ursolic Acid
chemical_list: D000900:Anti-Bacterial Agents; D009828:Oleanolic Acid; D012502:Sapogenins; D014315:Triterpenes; D000097245:Ursolic Acid; C054625:boswellic acid; C061014:cycloastragenol
keywords: Antibiotics; Staphylococcus aureus; antimicrobial activity; synergism; triterpenoids