Table 6 Antibiotic-potentiating active isoflavonoids.

From: Looking to nature for a new concept in antimicrobial treatments: isoflavonoids from Cytisus striatus as antibiotic adjuvants against MRSA

CIP

  

Neob

CorA

Orob

Gen

Tect

BiochA

Calyc

Irig

Gly

Daid

Irisfl

M116

MICa

20

2.5

120

>120

>120

>120

>120

>120

>120

>120

>120

MICb

5

—

60

60

60

30

—

—

—

15

—

R

2

—

8

4

2

4

—

—

—

2

—

FICI

0.75 (I)

I

0.63 (I)

≤0.50 (P)

>0.5 (I)

≤0.38 (P)

I

I

I

>0.5 (I)

I

RWW337

MICa

20

20

120

>120

>120

>120

>120

>120

>120

>120

>120

MICb

5

5

60

60

60

30

30

60

—

—

—

R

2

8

4

8

4

4

2

2

—

—

—

FICI

0.75 (I)

0.38 (S)

0.63 (I)

≤0.38 (P)

≤0.50 (P)

≤0.38 (P)

>0.5 (I)

>0.5 (I)

I

I

I

RWW50

MICa

20

2.5

120

>120

>120

>120

>120

>120

>120

>120

>120

MICb

10

—

—

30

60

15

30

30

—

—

—

R

4

—

—

2

2

2

2

2

—

—

—

FICI

0.75 (I)

I

I

>0.5 (I)

>0.5 (I)

>0.5 (I)

>0.5 (I)

>0.5 (I)

I

I

I

M82

MICa

20

2.5

60

>120

>120

>120

>120

>120

>120

>120

>120

MICb

10

1.25

—

30

30

30

—

60

—

—

—

R

4

2

—

2

2

2

—

2

—

—

—

FICI

0.75 (I)

1 (I)

I

>0.5 (I)

>0.5 (I)

>0.5 (I)

I

I

I

I

I

RN6390

MICa

20

2.5

60

>120

>120

>120

>120

>120

>120

>120

>120

MICb

10

—

—

—

—

—

—

—

-

—

—

R

4

—

—

—

—

—

—

—

—

—

—

FICI

0.75 (I)

I

I

I

I

I

I

I

I

I

I

CECT 976

MICa

20

2.5

60

>120

>120

>120

>120

>120

>120

>120

>120

MICb

10

—

—

30

60

60

60

60

—

30

60

R

2

—

—

4

2

2

2

2

—

2

2

FICI

1.0 (I)

I

I

≤0.38 (P)

>0.5 (I)

>0.5 (I)

>0.5 (I)

>0.5 (I)

I

>0.5 (I)

>0.5 (I)

SA1199B

MICa

20

0.06

60

>120

>120

>120

>120

>120

>120

>120

>120

MICb

5

—

15

60

60

30

60

60

60

60

60

R

4

—

2

8

4

8

4

4

2

4

4

FICI

0.50 (S)

I

>0.5 (I)

≤0.38 (P)

≤0.50 (P)

≤0.38 (P)

≤0.50 (P)

≤0.50 (P)

>0.5 (I)

≤0.25 (P)

≤0.50 (P)

ERY

M116

MICa

20

2.5

120

>120

>120

>120

>120

>120

>120

>120

>120

MICb

—

1.25

—

30

60

15

30

60

—

—

—

R

—

2

—

4

4

4

2

2

—

—

—

FICI

I

1 (I)

I

≤0.38 (P)

≤0.38 (P)

≤0.28 (P)

>0.5 (I)

>0.5 (I)

I

I

I

RWW337

MICa

20

20

120

240

>240

>240

>240

>240

>120

>120

>120

MICb

—

5

60

60

120

60

—

—

—

—

—

R

—

≥8

≥4

≥4

≥2

≥4

—

—

—

—

—

FICI

I*

≤0.38 (S)*

>0.50 (I)*

≤0.50 (P)*

(*)

≤0.50 (P)*

I*

I*

I

I

I

RWW50

MICa

20

2.5

120

>120

>120

>120

>120

>120

>120

>120

>120

MICb

10

—

—

60

60

60

30

60

—

—

—

R

8

—

—

4

4

4

2

2

—

—

—

FICI

0.63 (I)

I*

I*

≤0.50 (P)

≤0.50 (P)

≤0.50 (P)

>0.5 (I)

>0.5 (I)

I

I

I

M82

MICa

20

2.5

60

>120

>120

>120

>120

>120

>120

>120

>120

MICb

5

1.25

—

30

60

30

120

60

—

—

—

R

2

2

—

2

2

2

2

2

—

—

—

FICI

0.75 (I)

1 (I)

I

≥0.56 (I)

≥0.63 (I)

≥0.56 (I)

>0.5 (I)

>0.5 (I)

I

I

I

RN6390

MICa

20

2.5

60

>120

>120

>120

>120

>120

>120

>120

>120

MICb

10

—

—

—

—

—

—

—

—

—

—

R

4

—

—

—

—

—

—

—

—

—

—

FICI

0.75 (I)

I

I

I

I

I

I

I

I

I

I

CECT 976

MICa

20

2.5

60

>120

>120

>120

>120

>120

>120

>120

>120

MICb

—

1.25

—

30

60

—

60

60

—

—

—

R

—

2

—

4

2

—

2

2

—

—

—

FICI

I

1 (I)

I

≤0.38 (P)

>0.5 (I)

I

>0.5 (I)

>0.5 (I)

I

I

I

  1. Minimal inhibitory concentrations (MICs, µg/mL) of the isoflavonoids against clinical S. aureus, RN6390 and SA1199B when applied alone (MICa) and in combination (MICb) with ciprofloxacin or erythromycin. The MICs of antibiotics are shown in Table 1. Fold reductions of antibiotic MICs in the presence of each isoflavonoid are also represented (R) as well as Fractional Inhibitory Concentration Index (FICI) values. When FICI ≤ 0.5 (in bold), if the isoflavonoid has a determinable MIC value, the effect is considered as synergy (S); if the isoflavonoid has no detectable MIC, the effect is called potentiation (P). If FICI > 0.5, the interaction is considered indifferent (I). Nonactive isoflavonoids are not included. ERY was not tested against SA1199B. The values presented are the averages of three independent assays.
  2. = no decrease or increase in the MIC was observed; n.p. not performed; *no MIC was detected for erythromycin alone against RWW337, but when combined with genistein and biochanin A, erythromycin MIC was found to be at least ¼ of the maximal concentration tested, and at least ½ for tectorigenin. FICI = FIC(A) + FIC(B), with FIC(A) being the ratio between the MIC of drug A in combination and the MIC of drug A alone and FIC(B) the ratio of the MIC of drug B in combination and the MIC of drug B alone.
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