Antimicrobial activity of mul-1867, a novel antimicrobial compound, against multidrug-resistant Pseudomonas aeruginosa

BACKGROUND: There is an urgent need for new antimicrobial compounds to treat various lung infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR-PA). METHODS: We studied the potency of Mul-1867 against MDR-PA isolates from patients with cystic fibrosis, chronic obstructive pulmonary disease, and ventilator-associated pneumonia. The minimal inhibitory concentrations (MICs) and minimum biofilm eliminating concentrations (MBECs), defined as the concentrations of drug that kill 50 % (MBEC(50)), 90 % (MBEC(90)), and 100 % (MBEC(100)) of the bacteria in preformed biofilms, were determined by using the broth macrodilution method. RESULTS: Mul-1867 exhibited significant activity against MDR-PA and susceptible control strains, with MICs ranging from 1.0 to 8.0 µg/mL. Mul-1867 also possesses anti-biofilm activity against mucoid and non-mucoid 24-h-old MDR-PA biofilms. The MBEC(50) value was equal to onefold the MIC. The MBEC(90) value ranged from two to fourfold the MIC. Moreover, Mul-1867 completely eradicated mature biofilms at the concentrations tested, with MBEC(100) values ranging between 16- and 32-fold the MIC. Mul-1867 was non-toxic to Madin-Darby canine kidney (MDCK) cells at concentrations up to 256 µg/mL. CONCLUSION: Overall, these data indicate that Mul-1867 is a promising locally acting antimicrobial for the treatment and prevention of P. aeruginosa infections.