An “Unlikely” Pair: The Antimicrobial Synergy of Polymyxin B in Combination with the Cystic Fibrosis Transmembrane Conductance Regulator Drugs KALYDECO and ORKAMBI

Antibiotics may be combined with non-antibiotic drugs to increase their effectiveness without adding to drug-resistance. Pseudomonas aeruginosa is by far the most common infection that Cystic Fibrosis (CF) patients face. The infection can be particularly difficult to treat due to the mucus build-up that occurs in CF patients’ lungs, which gives bacteria a protective environment to thrive. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) that treats the underlying cause of CF, and Lumacaftor increases its effectiveness. Schneider et al. found that the combination of the CFTR drugs and polymyxin B showed synergistic in vitro activity against P. aeruginosa. They also investigated this antimicrobial mode of action, and found the bacterial outer membrane damage to be unique from the effect of each individual compound. This is an exciting new angle on the treatment of polymyxin-resistant lung infections.

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