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Molecules 2011, 16(12), 9819-9826; doi:10.3390/molecules16129819
Article

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

1,* , 1,2
,
1
,
3
,
1, 1
 and
4,*
1 Research Center for Natural Medicines, Kunming General Hospital, PLA, Kunming 650032, China 2 Kunming Medical College, Kunming 650032, China 3 School of Basic Medical Sciences, Yunnan Traditional Chinese Medical College, Kunming 650500, China 4 The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China
* Authors to whom correspondence should be addressed.
Received: 1 August 2011 / Revised: 11 October 2011 / Accepted: 8 November 2011 / Published: 25 November 2011
(This article belongs to the Section Natural Products)
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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.
Keywords: anti-MRSA; synergy; bisbenzylisoquinoline alkaloid; cefazolin; FICI anti-MRSA; synergy; bisbenzylisoquinoline alkaloid; cefazolin; FICI
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Zuo, G.-Y.; Li, Y.; Wang, T.; Han, J.; Wang, G.-C.; Zhang, Y.-L.; Pan, W.-D. Synergistic Antibacterial and Antibiotic Effects of Bisbenzylisoquinoline Alkaloids on Clinical Isolates of Methicillin-Resistant Staphylococcus Aureus (MRSA). Molecules 2011, 16, 9819-9826.

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