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.
Highlights
Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) have become the most common cause of infections among the global pathogenic bacteria, and many life-threatening diseases such as endocarditis, pneumonia and toxin shock syndrome are ascribed to them
We report for the first time the in vitro anti-MRSA and antibiotic synergistic effects of tetrandrine (Tet) and demethyltetrandrine (d-Tet) (Figure 1), two bisbenzylisoquinoline (BBIQ) alkaloids isolated from the Chinese drug Stephania tetrandra S
75–94%/75–88% compared with the agents used alone, which demonstrated significant antibacterial synergy activities against 90% of the tested pathogenic strains, with the fractional inhibitory concentration indices (FICIs) for Tet/CFZ
Summary
Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) have become the most common cause of infections among the global pathogenic bacteria, and many life-threatening diseases such as endocarditis, pneumonia and toxin shock syndrome are ascribed to them. We have been engaged in a search for plant-derived compounds active against multidrug resistant (MDR) bacteria from the Traditional Chinese Medicine (TCM) repertoire [7,8,9]. We report for the first time the in vitro anti-MRSA and antibiotic synergistic effects of tetrandrine (Tet) and demethyltetrandrine (d-Tet) (Figure 1), two bisbenzylisoquinoline (BBIQ) alkaloids isolated from the Chinese drug Stephania tetrandra S. Moore (Fen fang chi in Chinese), on MDR clinical isolates of MRSA and their synergistic effects with four antibiotics: ampicillin (AMP), azithromycin (AZM), cefazolin (CFZ) and levofloxacin (LEV)
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