Background: Pseudomonas aeruginosa is a gram-negative pathogen, associated with a severe
mortality rate. It is also difficult to treat due to numerous resistance mechanisms to a wide range of antibiotics.
Objective: Evaluate the activity of pexiganan, an antimicrobial peptide, in combination with two
clinical antibiotics (azithromycin and tigecycline) that are not active against P. aeruginosa.
Methods: Ten clinical P. aeruginosa were isolated from urinary tract infections, blood culture, skin infections
and respiratory tract infections. Minimum inhibitory concentrations (MICs) and synergies were
evaluated by broth microdilution, checkerboard assays and time-kill studies. In vitro synergy was confirmed
with an in vivo experiment using a murine model of sepsis.
Results: Pexiganan MICs were included between 2 and 16 mg/L. Tigecycline and azithromycin MICs
were high as expected (4-64 mg/L and 32-256 mg/L, respectively). Pexiganan and azithromycin combination
resulted to be additive or indifferent while tigecycline and pexiganan combination was synergic
against seven out of ten P. aeruginosa and additive against the other strains. In vivo experiment confirmed
the in vitro synergy, denoting a significative reduction of bacteria in mice treated with pexiganan
and tigecycline combination.
Conclusion: Antimicrobial peptides are molecules that could be useful in the fight against infections and
pexiganan seems to be one of the most promising. Our results demonstrated that, in association with tigecycline,
pexiganan administration could overcome antibiotic resistance and increase the effectiveness
of treatment against P. aeruginosa sepsis.