Efficacy Evaluation of Iclaprim in a Neutropenic Rat Lung Infection Model with Methicillin-Resistant Staphylococcus aureus Entrapped in Alginate Microspheres

Abstract

BackgroundThe objective of this study was to demonstrate the effect of iclaprim, a new generation diaminopyrimidine, in a neutropenic rat lung infection model with methicillin resistant Staphylococcus aureus (MRSA).Methods S. aureus strain AH1252, a thymidine knockout of the MRSA wild type AW6 strain, was utilized for this study. The bacterial strain was diluted in a 2% alginate buffer, which was added dropwise in a ratio of 1:5 into 50 mM MgCl to form alginate beads. The alginate beads reduce the efficacy of bacterial clearance similar to that seen in the cystic fibrosis population. A 5.25 × 104 bacterial inoculum was administered intratracheally to groups of 9 rats with prepared alginate bacteria suspensions, under isoflurane anesthesia. Beginning 2 hours post infection, rats received either iclaprim or vancomycin for 3 days via subcutaneous injection every 12 hours. Twelve hours after the last treatment, rats were euthanized and lungs collected for CFU determination.ResultsThe Table below shows survival, CFU/gram of lung, and change in CFUs (Standard Error of the Mean (S.E.M.) from baseline by treatment or vehicle group.ConclusionIn this rat lung infection model increased survival was observed in both iclaprim and vancomycin treatment groups, compared with the infection controls. Rats receiving iclaprim demonstrated a 5.34 log10 CFU reduction from the 72 hour infection whereas vancomycin-treated rats showed a 3.38 log10 CFU reduction from the 72 hour infection controls.#8232;Based on these data, further evaluation of iclaprim for S. aureus lung infections among the cystic fibrosis population is warranted.Disclosures D. Huang, Motif Bio: Employee, Salary