Study of Mul-1867, a drug candidate for inhalation therapy of pulmonary exacerbations in patients with cystic fibrosis against mixed infections caused by clinical isolates of P. aeruginosa, S. aureus and C. albicans in murine lung infection model.

Methods

8-weeks old C57BL/6 mice were intranasally infected with P. aeruginosa + S. aureus(each 1×105 cfu/mouse) or P. aeruginosa + C. albicans (each 1×105 cfu/mouse) mix. Treatment was started 12 h after infection with Mul-1867 or Amikacin (taken as representative of aminoglycosides that are used for the treatment of lung infections in CF patients), both administered by intranasal inhalation at 32×MIC.

Results

Mul-1867 exhibited a high level of antimicrobial activity with the MIC 0.25 mg/L against S.aureus; 0.5 mg/L against C. albicans and 4.0 mg/L against P. aeruginosa. Amikacin was less active; the MICs 128 mg/L for both S.aureus and P. aeruginosa and was not active against C. albicans. Induced pneumonia displayed a total death of control animals without of treatment within 72 h post-infection in both groups with mixed infections. For the group P. aeruginosa+ S.aureus treated with Mul-1867 to the end of observation period (72 h) 20% of mice died. Only 10% animals died in P.aeruginosa+C. albicans group treated with Mul-1867. Animals treated with Amikacin displayed 50% mortality in P. aeruginosa + S.aureus group and 70% mortality in P.aeruginosa + C. albicans.

Conclusion

Our study demonstrated that Mul-1867 possesses great activity against mixed infection, including bacterial–fungal mix.