Methods for treating pulmonary non-tuberculous mycobacterial infections
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 Mycobacterium avium complex (MAC) lung infection, comprising:
administering to the patient a macrolide antibiotic; and
administering to the lungs of the patient for an administration period of at least six months, a pharmaceutical composition comprising a liposomal suspension, wherein the liposomal suspension comprises an aminoglycoside, 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 via a nebulizer to provide an aerosolized pharmaceutical composition comprising a mixture of free aminoglycoside, or a pharmaceutically acceptable salt thereof, and liposomal complexed aminoglycoside, or a pharmaceutically acceptable salt thereof, and administering the aerosolized pharmaceutical composition via the nebulizer to the lungs of the patient once daily in a single dosing session during the administration period;
wherein during the administration period or subsequent to the administration period, the patient exhibits an NTM culture conversion to negative and walks an increased number of meters in the 6 minute walk test (6MWT), as compared to the number of meters walked by the patient prior to undergoing the treatment method.
2. The method of claim 1 , wherein prior to the treating, the patient was unresponsive to a different MAC therapy.
3. The method of claim 1 , prior to the treating, the patient was unresponsive to an American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) MAC guideline-based therapy (GBT).
4. The method of claim 3 , wherein prior to the treating, the patient was unresponsive to the ATS/IDSA MAC GBT for at least 6 months.
5. The method of claim 1 , wherein the macrolide antibiotic is azithromycin, clarithromycin, erythromycin, carbomycin A, josamycin, kitamycin, midecamycin, oleandomycin, solithromycin, spiramycin, troleandomycin, tylosin, roxithromycin, or a combination thereof.
6. The method of claim 5 , wherein the macrolide antibiotic is clarithromycin.
7. The method of claim 5 , wherein the macrolide antibiotic is azithromycin.
8. The method of claim 1 , further comprising administering to the patient a rifamycin compound.
9. The method of claim 8 , wherein the rifamycin compound is rifampin or rifabutin.
10. The method of claim 1 , further comprising administering to the patient ethambutol.
11. The method of claim 1 , wherein the electrically neutral phospholipid is an electrically neutral phosphatidylcholine.
12. The method of claim 11 , wherein the electrically neutral phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC).
13. The method of claim 1 , wherein during the single dosing session, the aerosolized pharmaceutical composition is administered in less than about 15 minutes.
14. The method of claim 1 , wherein during the single dosing session, the aerosolized pharmaceutical composition is administered in about 10 minutes to about 14 minutes.
15. The method of claim 1 , wherein the increased number of meters walked by the patient is at least about 5 meters.
16. The method of claim 1 , wherein the increased number of meters walked by the patient is at least about 20 meters.
17. The method of claim 15 , wherein the increased number of meters walked by the patient is from about 5 meters to about 50 meters.
18. The method of claim 13 , wherein the aminoglycoside or pharmaceutically acceptable salt thereof is amikacin, apramycin, arbekacin, astromicin, bekanamycin, boholmycin, brulamycin, capreomycin, dibekacin, dactimicin, etimicin, framycetin, gentamicin, H107, hygromycin, hygromycin B, inosamycin, K-4619, isepamicin, KA-5685, kanamycin, neomycin, netilmicin, paromomycin, plazomicin, ribostamycin, sisomicin, rhodestreptomycin, sorbistin, spectinomycin, sporaricin, streptomycin, tobramycin, verdamicin, vertilmicin, a pharmaceutically acceptable salt thereof, or a combination thereof.
19. The method of claim 18 , wherein the volume of the pharmaceutical composition is from about 8 mL to about 10 mL.