Antibiotic Formulations, Unit Doses, Kits, and Methods

Abstract

An aqueous or powder composition includes anti-gram-negative antibiotic or salt thereof being present at an amount ranging from about 100 mg/ml to about 200 mg/ml. Another aqueous or powder composition includes anti-gram-positive antibiotic or salt thereof being present at a concentration ranging from about 0.6 to about 0.9 of the water solubility limit, at 25° C. and 1.0 atmosphere, of the anti-gram-positive antibiotic or salt thereof. Other embodiments include unit doses, kits, and methods.

1 . An aqueous composition for aerosolization comprising amikacin being present at an amount from about 100 mg/ml to about 200 mg/ml. 
   
   
       2 . The aqueous composition of  claim 1 , wherein the aqueous composition consists essentially of amikacin and water. 
   
   
       3 . The aqueous composition of  claim 1 , wherein the amount amikacin is from about 110 mg/ml to about 150 mg/ml, or a potency from about 500 μg/mg to about 1100 μg/mg, or both. 
   
   
       4 . The aqueous composition of  claim 1 , wherein the aqueous composition has a pH from about 4 to about 6. 
   
   
       5 . The aqueous composition of  claim 1 , wherein the aqueous composition has an osmolality ranging from about 90 mOsmol/kg to about 500 mOsmol/kg. 
   
   
       6 . The aqueous composition of  claim 1 , wherein the aqueous composition is preservative-free. 
   
   
       7 . The aqueous composition of  claim 1 , further comprising an additional active agent. 
   
   
       8 . The aqueous composition of  claim 1 , further comprising an additional active agent selected from an anti-inflammatory and a bronchodilator. 
   
   
       9 . The aqueous composition of  claim 1 , further comprising a bronchodilator selected from β-agonist, anti-muscarinic agent, and steroid. 
   
   
       10 . The aqueous composition of  claim 1 , further comprising albuterol. 
   
   
       11 . The aqueous composition of  claim 1 , further comprising an osmolality adjuster. 
   
   
       12 . The aqueous composition of  claim 1 , wherein no precipitate forms in the aqueous composition when the aqueous composition is stored for 1 year at 25° C. 
   
   
       13 . The aqueous composition of  claim 1 , further comprising an anti-gram positive antibiotic. 
   
   
       14 . An aqueous composition, consisting essentially of amikacin, a bronchodilator, and water. 
   
   
       15 . The aqueous composition of  claim 14 , wherein the amikacin is present in an amount ranging from about 100 mg/ml to about 200 mg/ml. 
   
   
       16 . The aqueous composition of  claim 14 , wherein the aqueous composition has a pH from about 3 to about 7, and an osmolality from about 90 mOsmol/kg to about 500 mOsmol/kg. 
   
   
       17 . The aqueous composition of  claim 14 , wherein the bronchodilator is present in an amount of at least about 1 mg/ml. 
   
   
       18 . The aqueous composition of  claim 17 , wherein the bronchodilator is selected from a β-agonist, anti-muscarinic agent, and steroid. 
   
   
       19 . The aqueous composition of  claim 18 , wherein the bronchodilator comprises albuterol or salt thereof. 
   
   
       20 . A unit dose, comprising a container and an aqueous composition comprising amikacin, wherein the composition is preservative free. 
   
   
       21 . The unit dose of  claim 20 , wherein the amikacin is present at a concentration from about 90 mg/ml to about 200 mg/ml. 
   
   
       22 . A kit, comprising:
 a first container containing a first aqueous solution comprising a first antibiotic; and   a second container containing a second aqueous solution comprising a second antibiotic,   wherein the first antibiotic is amikacin and the second antibiotic is the same or different, and wherein a concentration, or an amount, or both of the first antibiotic is the same as, or different from a concentration, or an amount, or both of the second antibiotic.   
   
   
       23 . The kit of  claim 22 , wherein an amount of the first aqueous solution is from about 2 ml to about 5 ml, an amount of the second aqueous solution is from about 5 ml to about 8 ml, a concentration of first antibiotic is from about 100 mg/ml to about 120 mg/ml, and a concentration of second antibiotic is from about 120 mg/ml to about 140 mg/ml. 
   
   
       24 . The kit of  claim 23 , further comprising an aerosol introducer. 
   
   
       25 . The kit of  claim 28 , further comprising a vibrating mesh nebulizer. 
   
   
       26 . A kit, comprising:
 a first container containing a first aqueous solution comprising amikacin; and   a second container containing a second aqueous solution comprising an anti-gram-negative antibiotic,   wherein a concentration, an amount, or both, of the amikacin of the first aqueous solution is different from a concentration, or an amount, or both, of the anti-gram-negative antibiotic of the second aqueous solution.   
   
   
       27 . The kit of  claim 26 , further comprising an aerosol introducer. 
   
   
       28 . The kit of  claim 27 , further comprising a vibrating mesh nebulizer. 
   
   
       29 . A kit, comprising:
 a first container containing a first antibiotic comprising liquid amikacin; and   a second container containing a second antibiotic or salt thereof,   wherein the first and second antibiotics are the same or different, and wherein a concentration, or an amount, or both of the first antibiotic in the first container is different from a concentration, or an amount, or both, of the second antibiotic or salt thereof in the second container.   
   
   
       30 . The kit of  claim 29 , wherein the second antibiotic comprises a liquid. 
   
   
       31 . The kit of  claim 29 , wherein the second antibiotic comprises a powder. 
   
   
       32 . The kit of  claim 30 , wherein the liquid amikacin is preservative-free. 
   
   
       33 . The kit of  claim 29 , further comprising an aerosol introducer. 
   
   
       34 . The kit of  claim 33 , further comprising a vibrating mesh nebulizer. 
   
   
       35 . A method of administering an antibiotic formulation to a patient in need thereof, comprising:
 aerosolizing a liquid amikacin formulation to administer the antibiotic formulation to the pulmonary system of the patient, wherein the antibiotic formulation has a concentration of amikacin ranging from about 100 mg/ml to about 200 mg/ml.   
   
   
       36 . The method of  claim 35 , wherein the antibiotic formulation consists essentially of amikacin and water. 
   
   
       37 . The method of  claim 35 , wherein the aerosolizing comprises forming droplets having a mass median aerodynamic diameter of less than about 10 μm. 
   
   
       38 . The method of  claim 37 , wherein the aerosolizing comprises aerosolizing the antibiotic formulation in a vibrating mesh nebulizer. 
   
   
       39 . The method of  claim 35 , wherein the pulmonary administration comprises prophylactic treatment of ventilator associated pneumonia. 
   
   
       40 . A method of administering an antibiotic formulation to a patient in need thereof, comprising:
 inserting a tube into a trachea of a patient; and   aerosolizing an antibiotic formulation to administer the antibiotic formulation to the lungs of the patient,   wherein the antibiotic formulation consists essentially of amikacin and water.   
   
   
       41 . The method of  claim 40 , wherein the pulmonary administration comprises prophylactic treatment of ventilator associated pneumonia, hospital associated pneumonia, community acquired pneumonia, or combinations thereof. 
   
   
       42 . The method of  claim 40 , wherein the aerosolizing comprises aerosolizing the antibiotic formulation in a vibrating mesh nebulizer.