Table 6.
Antibiotic-potentiating active isoflavonoids.
| 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 | |
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.
= 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.