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 in a patient previously unresponsive to MAC therapy, comprising:
administering to the patient a macrolide antibiotic and a rifamycin compound; and
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 6 months,
wherein the treating comprises achieving a negative MAC sputum culture in the patient.
2. The method of claim 1 , wherein the patient is previously unresponsive to an American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) MAC guideline-based therapy (GBT).
3. The method of claim 2 , wherein the patient is previously unresponsive to the GBT for at least 6 months.
4. The method of claim 1 , wherein the patient has a non-cystic fibrosis underlying lung disease.
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 , wherein the rifamycin compound is rifampin.
9. The method of claim 1 , wherein the rifamycin compound is rifabutin.
10. The method of claim 1 , wherein the pharmaceutical composition comprises from about 500 mg to about 650 mg amikacin, or pharmaceutically acceptable salt thereof.
11. The method of claim 1 , wherein the amikacin or pharmaceutically acceptable salt thereof is amikacin sulfate.
12. The method of claim 1 , wherein the plurality of liposomes comprises unilamellar vesicles, multilamellar vesicles, or a mixture thereof.
13. The method of claim 1 , wherein the electrically neutral phospholipid is an electrically neutral phosphatidylcholine.
14. The method of claim 13 , wherein the electrically neutral phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC).
15. The method of claim 14 , wherein the pharmaceutical composition comprises about 70 mg/mL amikacin sulfate; about 30 to about 35 mg/mL DPPC; and about 15 to about 17 mg/mL cholesterol.
16. The method of claim 15 , wherein the pharmaceutical composition further comprises about 1.5% NaCl.
17. The method of claim 15 , wherein the pharmaceutical composition has a pH of about 6.5.
18. The method of claim 1 , wherein during the single dosing session, the aerosolized pharmaceutical composition is administered in less than about 15 minutes.
19. 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.
20. The method of claim 1 , wherein the treating comprises achieving MAC sputum culture conversion in the patient, wherein the MAC sputum culture conversion is defined as three consecutive negative MAC sputum cultures.