The combination of polymyxin B with sertraline exhibited in vitro synergistic activity against highly polymyxin-resistant Pseudomonas aeruginosa isolates from the lungs of patients with cystic fibrosis, according to research presented at American Society for Microbiology (ASM) Microbe 2019, held June 20-24, 2019, in San Francisco, California.

Using checkerboard and static time-kill assays against a panel of polymyxin-susceptible and polymyxin-resistant isolates from the lungs of patients with cystic fibrosis, researchers analyzed the efficacy of polymyxin B and sertraline individually and then together.

Individually, neither polymyxin B nor sertraline was effective against polymyxin-resistant (minimal inhibitory concentration, ≥32 mg/L) and polymyxin sensitive isolates (minimal inhibitory concentration, 1 mg/L).

When used together, however, the combination of clinically relevant concentrations of polymyxin B (0.25-4 mg/L) combined with sertraline (8-16 mg/L) demonstrated synergistic antibacterial activity. There was a statistically significant decrease in the bacterial count (colony-forming unit/mL) even after 24 hours. Scanning and transmission electron microscopy revealed that the combination created outer membrane damage to P aeruginosa cells that was distinct from the effect of each individual compound.

Novel combination therapies are needed for combating lung infections caused by superbugs like P aeruginosa, and therefore the synergistic activity exhibited by the combination of polymyxin B with sertraline “can be potentially useful for otherwise untreatable [cystic fibrosis] lung infections,” concluded the researchers.

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Disclosure: Elena K. Schneider-Futschik, PhD, is a consultant for Merck.

Reference

Hussein M, Karas J, Hoyer D, Li J, Schneider-Futschik EK, Velkov T. A novel antibiotic-non antibiotic combination strategy targeting multi-drug resistant gram-negative superbugs: polymyxin B in combination with the selective serotonin reuptake inhibitor sertraline. Presented at: ASM Microbe 2019; June 20-24, 2019; San Francisco, California. Poster P443.