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Table 3 MICs (mg/L) of magnolol (ML) and honokiol (HL) used alone and in combination with antibacterial agents against the ten MRSA strains

From: In vitro synergism of magnolol and honokiol in combination with antibacterial agents against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA)

Combinationa

Effect

MIC (mg/L)

FICIc

Interaction (n)d

Alone

Combined

TODb

Syn

Add

Ind

ML + AMK*

Range

8 + 32 ~ 32 + 128

2 + 4 ~ 8 + 32

8 + 16 ~ 2 + 2

0.375 ~ 0.75

8

2

0

 

50 %

16 + 64

2 + 8

4 + 4

0.5

   
 

90 %

16 + 64

4 + 32

4 + 4

0.625

   

ML + ETM

Range

8 + 4 ~ 32 + 16

1 + 1 ~ 8 + 4

16 + 8 ~ 2 + 4

0.313 ~ 0.75

8

2

0

 

50 %

16 + 8

2 + 2

4 + 4

0.375

   
 

90 %

16 + 16

4 + 2

2 + 4

0.75

   

ML + GEN*

Range

8 + 16 ~ 32 + 128

1 + 4 ~ 16 + 32

16 + 8 ~ 1 + 2

0.25 ~ 1.25

7

2

1

 

50 %

16 + 64

2 + 8

8 + 4

0.5

   
 

90 %

16 + 64

4 + 32

2 + 2

1

   

ML + FOS

Range

8 + 128 ~ 32 + 256

2 + 16 ~ 16 + 128

8 + 8 ~ 2 + 1

0.25 ~ 1.5

7

2

1

 

50 %

16 + 128

4 + 32

4 + 8

0.375

   
 

90 %

16 + 256

8 + 64

2 + 4

0.75

   

ML + CIP

Range

8 + 256 ~ 32 + 512

1 + 32 ~ 16 + 512

16 + 8 ~ 2 + 1

0.25 ~ 1.5

5

4

1

 

50 %

16 + 256

4 + 64

4 + 8

0.5

   
 

90 %

16 + 512

8 + 256

2 + 2

0.75

   

ML + LEV

Range

8 + 128 ~ 32 + 256

2 + 16 ~ 16 + 128

8 + 8 ~ 1 + 1

0.25 ~ 1.5

4

4

2

 

50 %

16 + 128

4 + 32

4 + 8

0.625

   
 

90 %

16 + 256

8 + 128

2 + 2

1.25

   

ML + NOR

Range

8 + 128 ~ 32 + 256

2 + 16 ~ 16 + 128

8 + 8 ~ 1 + 1

0.375 ~ 1.5

4

4

2

 

50 %

16 + 128

4 + 64

4 + 4

0.625

   
 

90 %

16 + 256

8 + 128

2 + 2

1.25

   

ML + PIP

Range

8 + 128 ~ 32 + 256

2 + 32 ~ 8 + 128

4 + 8 ~ 2 + 1

0.375 ~ 1.5

4

4

2

 

50 %

16 + 128

4 + 32

4 + 4

0.75

   
 

90 %

16 + 256

8 + 128

2 + 1

1.25

   

HL + ETM

Range

8 + 4 ~ 16 + 16

1 + 1 ~ 4 + 2

8 + 8 ~ 4 + 4

0.25 ~ 0.5

10

0

0

 

50 %

16 + 8

2 + 2

8 + 4

0.375

   
 

90 %

16 + 16

4 + 2

4 + 4

0.5

   

HL + AMK*

Range

8 + 32 ~ 16 + 128

1 + 4 ~ 4 + 32

8 + 8 ~ 4 + 2

0.25 ~ 0.75

9

1

0

 

50 %

16 + 64

2 + 8

8 + 4

0.375

   
 

90 %

16 + 64

4 + 32

4 + 4

0.5

   

HL + GEN*

Range

8 + 16 ~ 16 + 128

1 + 2 ~ 4 + 32

8 + 8 ~ 4 + 2

0.25 ~ 0.75

8

2

0

 

50 %

16 + 64

2 + 16

8 + 4

0.375

   
 

90 %

16 + 64

4 + 32

4 + 2

0.625

   

HL + FOS

Range

8 + 128 ~ 16 + 256

2 + 8 ~ 8 + 128

8 + 3 ~ 21 + 2

0.25 ~ 1.25

7

2

1

 

50 %

16 + 128

4 + 32

4 + 4

0.5

   
 

90 %

16 + 256

8 + 64

2 + 2

1

   

HL + CIP

Range

8 + 256 ~ 16 + 512

2 + 16 ~ 8 + 512

8 + 16 ~ 2 + 1

0.25 ~ 1.5

6

3

1

 

50 %

16 + 256

2 + 64

4 + 4

0.5

   
 

90 %

16 + 512

8 + 256

2 + 2

0.75

   

HL + LEV

Range

8 + 128 ~ 16 + 256

2 + 16 ~ 16 + 64

8 + 8 ~ 1 + 4

0.25 ~ 1.25

5

4

1

 

50 %

16 + 128

4 + 32

4 + 8

0.5

   
 

90 %

16 + 256

8 + 32

2 + 4

1.125

   

HL + PIP

Range

8 + 128 ~ 16 + 256

1 + 16 ~ 16 + 128

8 + 8 ~ 1 + 1

0.25 ~ 1.5

5

3

2

 

50 %

16 + 128

2 + 32

8 + 4

0.5

   
 

90 %

16 + 256

8 + 128

2 + 2

1.25

   

HL + NOR

Range

8 + 128 ~ 16 + 256

1 + 16 ~ 8 + 256

8 + 8 ~ 1 + 1

0.25 ~ 1.5

3

5

2

 

50 %

16 + 128

4 + 64

4 + 4

0.75

   
 

90 %

16 + 256

8 + 128

2 + 2

1.25

   
  1. aML Magnolol, HL Honokiol, AMK Amikacin, FOS Fosfomycin, LEV Levofloxacin, ETM Etilmicin, PIP Piperacillin, CIP Ciprofloxacin, NOR Norfloxacin, All data on the left side of “+” belong to ML or HL, and the data on the right side of “+” belong to the conventional antibacterial agents, for example, “ML + AMK” means ML combined with AMK. bTOD Times of dilution = MICAlone /MICCombined, ranged from the maximum to the minimum. cFICI Fractional inhibitory concentration index, dAdd Additivity (0.5 < FICI ≤ 1), Ind Indifference (1 < FICI ≤ 2), Syn Synergy (FICI ≤ 0.5). n’ Number of MRSA strains which showed the interactions. The total number is n = 10, e.g. n = n’(s) + n’(a) = 8 + 2 for ML + AMK combination in the first line in the table. *No statistically significant differences among the combinations of ML + AMK, ML + GEN, HL + AMK and HL + GEN (p >0.01)
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