Methods for treating pulmonary non-tuberculous mycobacterial infections

Abstract

Provided herein are methods for treating a pulmonary infection in a patient in need thereof, for example, a nontuberculous mycobacterial pulmonary infection for at least one treatment cycle. The method comprises administering to the lungs of the patient a pharmaceutical composition comprising a liposomal complexed aminoglycoside comprising a lipid component comprising electrically neutral lipids and an aminoglycoside. Administration comprises aerosolizing the pharmaceutical composition to provide an aerosolized pharmaceutical composition comprising a mixture of free aminoglycoside and liposomal complexed aminoglycoside, and administering the aerosolized pharmaceutical composition via a nebulizer to the lungs of the patient. The methods provided herein result in a change from baseline on the semi-quantitative scale for mycobacterial culture for a treated patient, and/or NTM culture conversion to negative during or after the administration period.

1 . A method for treating a nontuberculous mycobacterium (NTM) lung infection in a non-cystic fibrosis (CF) patient in need thereof, comprising:
 administering to the lungs of the patient, a pharmaceutical composition comprising amikacin, or a pharmaceutically acceptable salt thereof, encapsulated in a plurality of liposomes, wherein the lipid component of the plurality of liposomes consists of an electrically neutral phospholipid and cholesterol,   wherein administering to the lungs of the patient comprises aerosolizing the pharmaceutical composition to provide an aerosolized pharmaceutical composition comprising a mixture of free amikacin, or a pharmaceutically acceptable salt thereof, and liposomal complexed amikacin, or a pharmaceutically acceptable salt thereof, and administering the aerosolized pharmaceutical composition via a nebulizer to the lungs of the patient once daily in a single dosing session, for an administration period of at least 84 days,   wherein the treating comprises achieving a negative NTM sputum culture in the patient.   
     
     
         2 .- 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the amikacin or pharmaceutically acceptable salt thereof is amikacin sulfate. 
     
     
         8 . The method of  claim 1 , wherein the plurality of liposomes comprises unilamellar vesicles, multilamellar vesicles, or a mixture thereof. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the electrically neutral phospholipid is an electrically neutral a phosphatidylcholine. 
     
     
         11 . The method of  claim 10 , wherein the electrically neutral phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC). 
     
     
         12 .- 13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the volume of the pharmaceutical composition administered to the patient is from about 8 mL to about 10 mL. 
     
     
         15 . The method of  claim 1 , wherein the pharmaceutical composition comprises from about 500 mg to about 650 mg amikacin, or pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 1 , wherein the pharmaceutical composition is an aqueous dispersion. 
     
     
         17 .- 19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein during the single dosing session, the aerosolized pharmaceutical composition is administered in less than about 15 minutes. 
     
     
         21 . The method of  claim 20 , wherein during the single dosing session, the aerosolized pharmaceutical composition is administered in about 10 minutes to about 14 minutes. 
     
     
         22 .- 27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein the patient in need of treatment was previously unresponsive to NTM therapy. 
     
     
         29 .- 33 . (canceled) 
     
     
         34 . The method of  claim 1 , wherein the NTM lung infection is a  Mycobacterium abscessus  infection. 
     
     
         35 . The method of  claim 1 , wherein the NTM lung infection is  Mycobacterium avium  complex. 
     
     
         36 .- 89 . (canceled) 
     
     
         90 . The method of  claim 15 , wherein the pharmaceutical composition comprises from about 550 mg to about 625 mg amikacin, or pharmaceutically acceptable salt thereof. 
     
     
         91 . The method of  claim 15 , wherein the pharmaceutical composition comprises from about 550 mg to about 600 mg amikacin, or pharmaceutically acceptable salt thereof. 
     
     
         92 . The method of  claim 1 , wherein the treating comprises achieving NTM sputum culture conversion in the patient, wherein NTM sputum culture conversion is defined as three consecutive negative NTM sputum cultures. 
     
     
         93 . The method of  claim 1 , wherein the administration period is at least about 6 months. 
     
     
         94 . The method of  claim 94 , wherein the administration period is at least about 6 months. 
     
     
         95 . The method of  claim 34 , wherein the patient in need of treatment was previously unresponsive to NTM therapy. 
     
     
         96 . The method of  claim 35 , wherein the patient in need of treatment was previously unresponsive to NTM therapy.