Formulations of aminoglycoside and fosfomycin combinations and methods and systems for treatment of ventilator associated pneumonia (vap) and ventilator associated tracheal (vat) bronchitis

Abstract

The present invention is antibiotic compositions, ventilator-based systems and methods relating to ventilator-associated pneumonia (VAP) and ventilator-associated tracheal (VAT) bronchitis. Antibiotic combinations of fosfomycin and an aminoglycoside, preferably amikacin, are administered via an inline nebulizer within the airway of the ventilator. Humidified conditions create an improved aerosol mist to treat VAP and VAT.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising:
 a bactericidal concentration of amikacin and fosfomycin combined in a hypertonic solution at a ratio of amikacin:fosfomycin greater than 1:1 and having at least about 30 equil/L of permeant anion.   
     
     
         2 . The composition of  claim 1 , wherein the osmolality of the solution is less than about 1,000 mOsmol/L. 
     
     
         3 . The composition of  claim 1 , wherein the concentration of amikacin is at least 50 mg/ml. 
     
     
         4 . The composition of  claim 1 , wherein the concentration of fosfomycin is at least about 20 mg/ml. 
     
     
         5 . The composition of  claim 1 , having a pH between about 4.4 and about 7.5. 
     
     
         6 . The composition of  claim 1 , wherein the concentration of permeant anion is at least about 40 mEq/L and an osmolality is between about 310 mOsmol/L and less than about 800 mOsmol/L. 
     
     
         7 . The composition of  claim 1 , wherein the solution contain between 100 and 300 mg fosfomycin. 
     
     
         8 . The composition of  claim 1 , wherein the solution contains between 150 and 600 mg amikacin. 
     
     
         9 . The composition of  claim 1 , wherein the fosfomycin is a water soluble salt thereof. 
     
     
         10 . The composition of  claim 6 , wherein the permeant anion is chloride.