Table 3.
Antimicrobial activity of the RFR-ChBac3.4(1-14)-NH2 analogue in combination with conventional antibiotics against drug-resistant clinical isolates compared to native ChBac3.4.
| Minimal FICIs a of antibiotic(AB)\AMP combinations against drug-resistant clinical isolates | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Gram-negative: | Gram-positive: | |||||||||
| E. coli ESBL 521/17 | A. baumannii 7226/16 | P. aeruginosa MDR 522/17 | K. pneumoniae ESBL 344/17 | S. aureus 1399/17 | ||||||
| AB\AMP | ChBac3.4 b | RFR-ChBac3.4(1–14) | ChBac3.4 b | RFR-ChBac3.4(1–14) | ChBac3.4 b | RFR-ChBac3.4(1–14) | ChBac3.4 b | RFR-ChBac3.4(1–14) | ChBac3.4 b | RFR-ChBac3.4(1–14) |
| OX | 1.12 | 1.12 | 1.12 | 1.12 | 1.12 | 1.12 | 1.12 | 1.12 | 0.25 | 0.31– |
| MEM | 1.0 | 1.12 | 0.5 | 0.5= | 0.62 | 0.38! | 1.0 | 0.75 | 0.31 | 0.62! |
| ERY | 0.38 | 0.38= | 0.75 | 0.25! | 0.38 | 0.19+ | 0.25 | 0.06+ | 0.5 | 0.28+ |
| AMK | 0.62 | 0.75 | 0.5 | 0.19+ | 0.5 | 0.38+ | 0.38 | 0.31+ | 0.125 | 0.19– |
| OFL | 0.75 | 0.56 | 0.5 | 0.5= | 0.75 | 0.31! | 0.75 | 0.25! | 0.125 | 0.5– |
AMP, antimicrobial peptide; AB, antibiotic; OX, oxacillin; MEM, meropenem; ERY, erythromycin; AMK, amikacin; OFL, ofloxacin.
Fractional Inhibitory Concentration Indices (FICI) values are medians of 3–4 independent experiments; minFICI > 2 indicates antagonism, 1 < minFICI ≤ 2 shows independent action, 0.5 < minFICI ≤ 1 corresponds to additivity, minFICI ≤ 0.5 denotes synergy; synergy cases are set off in bold type.
Data on ChBac3.4 antimicrobial activity in combinations with antibiotics, taken from (Zharkova et al., 2019), are sown for easier comparison.
Lower FICIs illustrate more intense synergistic interaction. The cases where synergy demonstrated by an antibiotic in combination with RFR-ChBac3.4(1-14)-NH2 is similar to, or stronger or lower than that in combination with native ChBac3.4 are marked “=“, “+” and “–”, respectively. Cases of synergy that exclusively emerged (or were lost) for combinations with RFR-ChBac3.4(1-14)-NH2 are indicated by “!”.