Compositions and methods for treating bacterial infections using ceftaroline

Abstract

The present invention relates to compositions comprising ceftaroline or a prodrug thereof (e.g., ceftaroline fosamil) and methods for treating bacterial infections, such as complicated skin and structure infections (cSSSI) and community-acquired bacterial pneumonia (CABP) by administering ceftaroline or a prodrug thereof, (e.g., ceftaroline fosamil).

1 - 23 . (canceled) 
     
     
         24 . A method of treating a bacterial infection in a patient in need thereof, comprising: (a) providing a dosage form comprising about 200 mg to about 600 mg ceftaroline fosamil; (b) constituting the dosage form using a diluent to make a constituted solution with a pH of about 4.8 to about 6.5; (c) preparing an infusion solution using the constituted solution; and (d) administering the infusion solution to the patient over a period of about one hour; wherein the patient has a creatinine clearance of about ≦50 ml/min. 
     
     
         25 . The method of  claim 24 , wherein the bacterial infection is a complicated skin and skin structure infection. 
     
     
         26 . The method of  claim 25 , wherein the complicated skin and skin structure infection is due to a microorganism selected from the group consisting of  Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus, Streptococcus intermedius, Streptococcus constellatus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca  and  Morganella morganii.    
     
     
         27 . The method of  claim 24 , wherein the bacterial infection is community-acquired bacterial pneumonia. 
     
     
         28 . The method of  claim 27 , wherein the community-acquired bacterial pneumonia is due to a microorganism selected from the group consisting of  Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca  and  Escherichia coli.    
     
     
         29 . The method of  claim 24 , wherein about 400 mg ceftaroline fosamil is administered to the patient. 
     
     
         30 . The method of  claim 24 , wherein about 300 mg ceftaroline fosamil is administered to the patient. 
     
     
         31 . The method of  claim 24 , wherein about 200 mg ceftaroline fosamil is administered to the patient. 
     
     
         32 . A method of treating a bacterial infection in a patient in need thereof, comprising: (a) providing a dosage form comprising about 600 mg of ceftaroline fosamil; (b) constituting the dosage form using a diluent to make a constituted solution with a pH of about 4.8 to about 6.5; (c) preparing an infusion solution using the constituted solution; and (d) administering the infusion solution to the patient over a period of about one hour; wherein the dosage form provides an in vivo plasma profile for ceftaroline comprising a Cmax of about 15 to about 30 μg/ml and an AUC of about 45 to about 75 μg h/ml. 
     
     
         33 . The method of  claim 32 , wherein the bacterial infection is a complicated skin and skin structure infection. 
     
     
         34 . The method of  claim 33 , wherein the complicated skin and skin structure infection is due to a microorganism selected from the group consisting of  Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus, Streptococcus intermedius, Streptococcus constellatus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca  and  Morganella morganii.    
     
     
         35 . The method of  claim 32 , wherein the bacterial infection is community-acquired bacterial pneumonia. 
     
     
         36 . The method of  claim 35 , wherein the community-acquired bacterial pneumonia is due to a microorganism selected from the group consisting of  Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca  and  Escherichia coli.    
     
     
         37 . A pharmaceutical composition for treatment of a bacterial infection comprising about 200 mg to about 800 mg ceftaroline fosamil; L-arginine; and less than about 2% of an L-arginine adduct. 
     
     
         38 . The pharmaceutical composition of  claim 37 , wherein the L-arginine adduct is a compound of formula I: 
       
         
           
           
               
               
           
         
       
     
     
         39 . The pharmaceutical composition of  claim 37 , wherein the L-arginine adduct is a compound of formula II: 
       
         
           
           
               
               
           
         
       
     
     
         40 . The composition according to  claim 37 , wherein the composition provides a mean AUC for ceftaroline in patients with a creatinine clearance from about 50 to about 80 ml/min of about 1.2 times greater than a mean AUC for ceftaroline in patients with a creatinine clearance of greater than about 80 ml/min. 
     
     
         41 . The composition according to  claim 37 , wherein the composition provides a mean AUC of ceftaroline in patients with a creatinine clearance from about 30 to about 50 ml/min of about 1.5 times greater than a mean AUC for ceftaroline in patients with a creatinine clearance of greater than about 80 ml/min.