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, mu g/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.
[1]PLA, Kunming Gen Hosp, Res Ctr Nat Med, Kunming 650032, Peoples R China.
[2]Kunming Med Coll, Kunming 650032, Peoples R China.
[3]Yunnan Tradit Chinese Med Coll, Sch Basic Med Sci, Kunming 650500, Peoples R China.
[4]Key Lab Chem Nat Prod Guizhou Prov, Guiyang 550002, Peoples R China.
[5]Chinese Acad Sci, Guiyang 550002, Peoples R China.
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