Synergistic antibacterial and antibiotic effects of bisbenzylisoquinoline alkaloids on clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA)

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...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2011-11, Vol.16 (12), p.9819-9826
Main Authors: Zuo, Guo-Ying, Li, Yang, Wang, Tao, Han, Jun, Wang, Gen-Chun, Zhang, Yun-Ling, Pan, Wei-Dong
Format: Article
Language:English
Subjects:
Alkaloids - chemistry
Alkaloids - pharmacology
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
anti-MRSA
Antibiotics
Bacteria
Benzylisoquinolines - pharmacology
bisbenzylisoquinoline alkaloid
cefazolin
Drug Synergism
Electronic mail systems
FICI
Humans
Methicillin-Resistant Staphylococcus aureus - drug effects
Methicillin-Resistant Staphylococcus aureus - isolation & purification
Microbial Sensitivity Tests
Natural products
Phytochemicals
Pneumonia
Staphylococcus infections
synergy
Time Factors
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Summary: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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules16129819