## 2 Results and Discussion
### Peptoid-Antibiotic Interaction Study  
It has been shown that the co-administration of CAMPs and antibiotics often provides synergic effects [60; 61]. In particular, a recent study [61] showed that synergy is most likely to be observed when combining CAMPs with high levels of membrane-damaging activity and antibiotics with intracellular targets (e.g., DNA and protein synthesis inhibitors). It is likely that the membrane damage caused by the CAMPs could favor the penetration of antibiotics, thus enhancing their action. Based on these observations, we measured the Fractional Inhibitory Concentration Index (FIC\({}_{\text{i}}\)) of P13#1 on _P. aeruginosa_ PAO1 and _S. aureus_ ATCC 6538P and antibiotics belonging to four different classes, namely, tobramycin (an aminoglycosoxide), ciprofloxacin (a fluoroquinolone), meropenem (a \(\beta\)-lactam antibiotic) and colistin (a polymysxin) (Table 2).  
Usually, an FIC\({}_{\text{i}}\) < 0.5 is considered a clear indication of synergy, values between 0.5 and 1 are considered indicative of additivity, values between 1 and 2 are considered indicative of indifference and values > 2 are indicative of antagonism [62; 63]. Except for meropenem, all the measured values were lower than 1, thus indicating additivity/synergy. In particular, the combination of P13#1 + colistin showed an FIC\({}_{\text{i}}\) value well below 0.5, thus highlighting a strong synergistic effect. It is worth noting that synergy with colistin has also been found frequently with other CAMPs [43; 60; 64; 65]. As polymysins specifically damage the outer membranes of Gram(\(-\)) strains, it can be speculated that they could favor the penetration into the wall of other CAMPs which, differently from polymysxins, can also damage the inner membrane. This combined action would explain the strong  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Bacterial Strains** & **Antibiotic** & **MIC (\#g/mL)** & **ZFIC\({}_{\text{i}}\)1** \\ \hline \hline \multicolumn{3}{c}{**P13\#1**} \\ \hline
**Gram(\(-\))** & & & \\ _Pseudomonas aeruginosa_ PAO1 & **Tobramycin** & 0.0078 & 0.626 \\  & **Ciprofloxacin** & 0.125 & 0.750 \\  & **Colistin** & 0.25 & 0.376 \\  & **Meropenem** & 0.25 & 2 \\ \hline
**Gram(+)** & & & \\ _Staphylococcus aureus_ ATCC 6538P & **Tobramycin** & 0.00097 & 0.750 \\  & **Ciprofloxacin** & 0.125 & 1 \\  & **Meropenem** & 0.0625 & 2 \\ \hline \hline \end{tabular} \({}^{\dagger}\) Fractional inhibitory concentration index (FIC\({}_{\text{i}}\)) values were determined for P13#1 in combination with antibiotics on Gram(+) and Gram(\(-\)) strains. The indexes were obtained from a minimum of three independent experiments, each one carried out in triplicate.  
\end{table}
Table 2: Combination therapy analysis.  
synergistic effect [64]. Also, the observation that FIC\({}_{\text{i}}\) values close to 0.5 were found for the P13#1 + tobramycin combination is particularly interesting for the potential pharmacological applications of P13#1. As aerosolized tobramycin and colistin are frequently used to treat airway infections (e.g., in the case of cystic fibrosis patients who develop _P. aeruginosa_ infections [66]), it is possible to conceive of combination treatments consisting of these antibiotics and P13#1.