Systems for treating pulmonary infections

Abstract

Provided herein are systems for treating a subject with a pulmonary infection, for example, a nontuberculous mycobacterial pulmonary infection, a Burkholderia pulmonary infection, a pulmonary infection associated with bronchiectasis, or a Pseudomonas pulmonary infection. The system includes a pharmaceutical formulation comprising a liposomal aminoglycoside dispersion, and the lipid component of the liposomes consist essentially of electrically neutral lipids. The system also includes a nebulizer which generates an aerosol of the pharmaceutical formulation at a rate greater than about 0.53 gram per minute. The aerosol is delivered to the subject via inhalation for the treatment of the pulmonary infection.

1 .- 146 . (canceled) 
     
     
         147 . A method for treating against a nontuberculous mycobacterial (NTM) pulmonary infection in a patient, the method comprising:
 aerosolizing a pharmaceutical formulation comprising an aminoglycoside or pharmaceutically acceptably salt thereof encapsulated in liposomes, with a nebulizer comprising a vibrating mesh membrane at a rate of 0.60 g per minute to 0.80 g per minute, to form an aerosolized pharmaceutical formulation, wherein the lipid component of the liposomes consists of dipalmitoylphosphatidylcholine (DPPC) and cholesterol and is present at 45-60 mg/mL, and the aminoglycoside or pharmaceutically acceptable salt thereof is present at about 500 mg to about 650 mg, and   administering the aerosolized pharmaceutical formulation to the lungs of the patient in a single dosing session;   wherein the aerosolized pharmaceutical formulation comprises a mixture of free aminoglycoside and liposomal complexed aminoglycoside, the fine particle fraction (FPF) of the aerosolized pharmaceutical formulation is greater than or equal to about 64%, as measured by the Andersen Cascade Impactor (ACI), or greater than or equal to about 51%, as measured by the Next Generation Impactor (NGI) and the percent liposomal complexed aminoglycoside of the aerosolized pharmaceutical formulation is from 60% to 70%.   
     
     
         148 . The method of  claim 147 , wherein the aminoglycoside is amikacin, apramycin, arbekacin, astromicin, capreomycin, dibekacin, framycetin, gentamicin, hygromycin B, isepamicin, kanamycin, neomycin, netilmicin, paromomycin, ribostamycin, sisomicin, rhodestreptomycin, spectinomycin, streptomycin, tobramycin, verdamicin, a pharmaceutically acceptable salt thereof, or a combination thereof. 
     
     
         149 . The method of  claim 147 , wherein the aminoglycoside is amikacin. 
     
     
         150 . The method of  claim 147 , wherein the aminoglycoside is amikacin sulfate. 
     
     
         151 . The method of  claim 147 , wherein the fine particle fraction (FPF) of the aerosolized pharmaceutical formulation is about 64% to about 80%, as measured by the ACI; or about 51% to about 65%, as measured by the NGI. 
     
     
         152 . The method of  claim 148 , wherein the fine particle fraction (FPF) of the aerosolized pharmaceutical formulation is about 64% to about 80%, as measured by the ACI; or about 51% to about 65%, as measured by the NGI. 
     
     
         153 . The method of  claim 149  wherein the fine particle fraction (FPF) of the aerosolized pharmaceutical formulation is about 64% to about 80%, as measured by the ACI; or about 51% to about 65%, as measured by the NGI. 
     
     
         154 . The method of  claim 150 , wherein the fine particle fraction (FPF) of the aerosolized pharmaceutical formulation is about 64% to about 80%, as measured by the ACI; or about 51% to about 65%, as measured by the NGI. 
     
     
         155 . The method of  claim 147 , wherein the nontuberculous mycobacterial pulmonary infection is  M. avium, M. avium  subsp.  hominissuis  (MAH),  M. abscessus, M. chelonae, M. bolletii, M. kansasii, M. ulcerans, M. avium, M. avium  complex (MAC),  M. conspicuum, M. kansasii, M. peregrinum, M. immunogenum, M. xenopi, M. marinum, M. malmoense, M. marinum, M. mucogenicum, M. nonchromogenicum, M. scrofulaceum, M. simiae, M. smegmatis, M. szulgai, M. terrae, M. terrae  complex,  M. haemophilum, M. genavense, M. asiaticum, M. shimoidei, M. gordonae, M. nonchromogenicum, M. triplex, M. lentiflavum, M. celatum, M. fortuitum  or  M. fortuitum  complex. 
     
     
         156 . The method of  claim 147 , wherein the nontuberculous mycobacterial pulmonary infection is  M. avium  complex (MAC). 
     
     
         157 . The method of  claim 148 , wherein the nontuberculous mycobacterial pulmonary infection is  M. avium  complex (MAC). 
     
     
         158 . The method of  claim 149 , wherein the nontuberculous mycobacterial pulmonary infection is  M. avium  complex (MAC). 
     
     
         159 . The method of  claim 150 , wherein the nontuberculous mycobacterial pulmonary infection is  M. avium  complex (MAC). 
     
     
         160 . The method of  claim 151 , wherein the nontuberculous mycobacterial pulmonary infection is  M. avium  complex (MAC). 
     
     
         161 . The method of  claim 152 , wherein the nontuberculous mycobacterial pulmonary infection is  M. avium  complex (MAC). 
     
     
         162 . The method of  claim 153 , wherein the nontuberculous mycobacterial pulmonary infection is  M. avium  complex (MAC). 
     
     
         163 . The method of  claim 154 , wherein the nontuberculous mycobacterial pulmonary infection is  M. avium  complex (MAC). 
     
     
         164 . The method of  claim 147 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         165 . The method of  claim 148 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         166 . The method of  claim 149 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         167 . The method of  claim 150 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         168 . The method of  claim 151 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         169 . The method of  claim 152 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         170 . The method of  claim 153 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         171 . The method of  claim 154 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         172 . The method of  claim 155 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         173 . The method of  claim 156 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         174 . The method of  claim 157 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         175 . The method of  claim 158 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI. 
     
     
         176 . The method of  claim 159 , wherein the MMAD of the aerosol is about 3.2 μm to about 4.2 μm, as measured by the ACI; or about 4.4 μm to about 4.9 μm, as measured by the NGI.