The rapid emergence of antimicrobial resistance in coupled with the dried pipeline of novel treatments has driven the search for new therapeutic modalities. Gram-negative Bacteria have an extra outer membrane that serves as a permeability barrier for various hydrophobic and/or large compounds. One of the popular approaches to tackle this penetration barrier is use of potentiators or adjuvants in combination with traditional antibiotics. This study reports the in vitro potential of an antimicrobial peptide Tridecaptin M in combination with other antibiotics against different strains of . Tridecaptin M sensitized the Bacteria to rifampicin, vancomycin, and ceftazidime. Further, we observed that a Tridecaptin M and rifampicin combination killed the Bacteria completely in 4 h in an ex vivo blood infection model and was superior to rifampicin monotherapy. The study also found that concomitant administration of both compounds is not necessary to achieve the antimicrobial effect. Bacteria pre-treated with Tridecaptin M (for 2-4 h) followed by exposure to rifampicin showed similar killing as obtained for combined treatment. Additionally, this combination hampered the survival of persister development in comparison to rifampicin alone. These findings encourage the future investigation of this combination to treat severe infections caused by extremely drug-resistant .
