title: Synergistic antibacterial and antibiotic effects of bisbenzylisoquinoline alkaloids on clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).
abstract: The antibacterial activity of two bisbenzylisoquinoline alkaloids, tetrandrine (Tet) and demethyltetrandrine (d-Tet), alone and in combination with the antibiotics ampicillin (AMP), azithromycin (AZM), cefazolin (CFZ) and levofloxacin (LEV) against 10 clinical isolates of staphylococcal chromosomal cassette mec (SCCmec) III type methicillin-resistant Staphylococcus aureus (MRSA) was studied. Susceptibility to each agent alone was tested using a broth microdilution method. The chequerboard and time-kill tests were used for the combined evaluations. The minimal inhibitory concentrations/minimal bactericidal concentrations (MICs/MBCs, μg/mL) ranges alone were 64-128/256-1,024 for both Tet and d-Tet. Significant synergies against 90% of the isolates were observed for the Tet/CFZ combination, with their MICs being reduced by 75-94% [fractional inhibitory concentration indices (FICIs) ranged from 0.188 to 0.625], respectively. An additive bactericidal result was also observed for the Tet (d-Tet)/CFZ combination in the time-kill experiments. These results demonstrated that Tet and d-Tet enhanced the in vitro inhibitory efficacy of CFZ. Their potential for combinatory therapy of patients infected with MRSA warrants further pharmacological investigation.
authors: Research Center for Natural Medicines, Kunming General Hospital, PLA, Kunming 650032, China. zuoguoying@263.net
authors: Guo-Ying
authors: GY
authors: Zuo
authors: Yang
authors: Y
authors: Li
authors: Tao
authors: T
authors: Wang
authors: Jun
authors: J
authors: Han
authors: Gen-Chun
authors: GC
authors: Wang
authors: Yun-Ling
authors: YL
authors: Zhang
authors: Wei-Dong
authors: WD
authors: Pan
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification*; D008826:Microbial Sensitivity Tests; D013997:Time Factors
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D044182:Benzylisoquinolines; C009438:tetrandrine