title: In vitro activity of sodium new houttuyfonate alone and in combination with oxacillin or netilmicin against methicillin-resistant Staphylococcus aureus.
abstract: BACKGROUND
  Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA.
  
  
  METHODS
  A total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays.
  
  
  RESULTS
  SNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥ 2log(10) CFU/mL.
  
  
  CONCLUSIONS
  SNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. The SNH-based combinations showed promise in combating MRSA.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.forename: Xinyi
authors.initials: X
authors.lastname: Yang
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Ren
authors.forename: Longyin
authors.initials: L
authors.lastname: Zhao
authors.forename: Xinxin
authors.initials: X
authors.lastname: Hu
authors.forename: Jiandong
authors.initials: J
authors.lastname: Jiang
authors.forename: Xuefu
authors.initials: X
authors.lastname: You
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003428:Cross Infection / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009428:Netilmicin / Q000494:pharmacology*; D010068:Oxacillin / Q000494:pharmacology*; D013045:Species Specificity; D013451:Sulfonic Acids / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D013451:Sulfonic Acids; C556396:lauroyl-alpha-hydroxyethyl sulfonic acid; D009428:Netilmicin; D010068:Oxacillin