Synergistic Antibacterial and Antibiotic Effects of Bisbenzylisoquinoline Alkaloids on Clinical Isolates of Methicillin-Resistant Staphylococcus Aureus (MRSA)

• Main Authors: Wei-Dong Pan, Yun-Ling Zhang, Gen-Chun Wang, Tao Wang, Jun Han, Yang Li, Guo-Ying Zuo
• Format: Article
• Language: English
• Published: MDPI AG 2011-11-01
• Series: Molecules
• Subjects: anti-MRSA; synergy; bisbenzylisoquinoline alkaloid; cefazolin; FICI
• Online Access: http://www.mdpi.com/1420-3049/16/12/9819/

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.