-- Low potency against P. aeruginosa
-- Lack of activity against other common CF pathogens
-- Potential for rapid resistance development
-- Suboptimal activity in biofilms, a factor that contributes to chronic
infections in CF patients
-- Reduced potency in anaerobic environments common in the CF lung from
thickened mucous layers
-- Reduced antibacterial activity in CF sputum
-- Inconvenient dosing regimens that reduce patient compliance
Preclinical results presented at the meetings this week show MP-376
offers potentially substantial improvements in each of these areas:
-- Potency: MIC90s for MP-376 against nearly 300 P. aeruginosa clinical
isolates from CF patients were at least 4-fold lower than those obtained
for tobramycin, amikacin and aztreonam.
-- Spectrum: MIC90s for MP-376 against clinical isolates for other common
CF pathogens such as B. cepacia, S. maltophilia and A. xylosoxidans were
substantially lower than for these other antibiotics. Previous in vitro
work has also shown superior potency of MP-376 compared to other agents
against gram positive bacteria commonly found in CF patients.
-- Resistance: in an in vitro model of resistance development in P.
aeruginosa, doses of levofloxacin formulated as MP-376 at levels
consistent with that which can be achieved with aerosol administrations
demonstrated rapid bacterial killing with no development of resistance
over the course of 4 days. In contrast, doses of levofloxacin mimicking
human exposures following systemic administration showed initial
bacterial killing, but allowed for resistance development within 24
hours. This demonstrates the importance o
|SOURCE Mpex Pharmaceuticals, Inc.|
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