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.

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.

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.

It was found that finafloxacin eradicates pathogens from patients suffering from bacterial infections like urinary tract infections and pyelonephritis more quickly than other fluoroquinolones regularly used for the treatment of these patients. Due to the efficacy of finafloxacin reduced treatment durations without increasing the daily dosage of finafloxacin and at the same time no or shorter stays in hospital are realizable, thus improving patient convenience and significantly lowering the costs of hospitalization and treatment. Reduced hospitalization periods do also clearly reduce the risk of nosocomial infections and of generating drug-resistant strains through extended therapy. The inventive treatment regimens comprise an oral finafloxacin administration for 1-5 days or a parenteral finafloxacin administration for 1-5 days for use in the treatment of a complicated urinary tract infection or pyelonephritis. However, a prior short parenteral administration of finafloxacin (e.g. 3 days) in combination with an oral administration (e.g. 2 days) may be applied, if necessary in case of really severe infections. The present invention further relates to a novel treatment regime for the treatment of uncomplicated UTI whereby a single oral finafloxacin dose is considered to be sufficient to effectively treat patients with uncomplicated UTI.

It was found that finafloxacin eradicates pathogens from patients suffering from bacterial infections like urinary tract infections and pyelonephritis more quickly than other fluoroquinolones regularly used for the treatment of these patients. Due to the efficacy of finafloxacin reduced treatment durations without increasing the daily dosage of finafloxacin and at the same time no or shorter stays in hospital are realizable, thus improving patient convenience and significantly lowering the costs of hospitalization and treatment. Reduced hospitalization periods do also clearly reduce the risk of nosocomial infections and of generating drug-resistant strains through extended therapy. The inventive treatment regimens comprise an oral finafloxacin administration for 1-5 days or a parenteral finafloxacin administration for 1-5 days for use in the treatment of a complicated urinary tract infection or pyelonephritis. However, a prior short parenteral administration of finafloxacin (e.g. 3 days) in combination with an oral administration (e.g. 2 days) may be applied, if necessary in case of really severe infections. The present invention further relates to a novel treatment regime for the treatment of uncomplicated UTI whereby a single oral finafloxacin dose is considered to be sufficient to effectively treat patients with uncomplicated UTI.

This invention pertains to a crystalline compound of Formula (A) as described herein and compositions containing this crystalline compound, as well as methods of using the compound or pharmaceutical compositions comprising it to treat bacterial infections. The compound and compositions are especially useful to treat Gram negative bacterial infections, including multi-drug resistant strains.

##STR00001##

This invention pertains to a crystalline compound of Formula (A) as described herein and compositions containing this crystalline compound, as well as methods of using the compound or pharmaceutical compositions comprising it to treat bacterial infections. The compound and compositions are especially useful to treat Gram negative bacterial infections, including multi-drug resistant strains.

##STR00001##

Pharmaceutical compositions comprising a SARS-CoV-2 E protein channel blocker and ORF3 inhibitors for treating or preventing SARS-CoV-2 virulence in a subject, are provided. Further provides is a pharmaceutical composition comprising a SARS-CoV-2 E protein channel blocker or an ORF3 inhibitor for preventing SARS-CoV-2 cell entry, uncoating and/or release from a cell.

The disclosure includes compounds of Formula (A): ##STR00001##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10, R.sub.11, and R.sub.12, j, k, m, n, Y, W, W.sub.1, W.sub.2, W.sub.3, V, L, Z.sub.1, Q.sub.1, Q.sub.2, Q.sub.3, and Q.sub.4, are defined herein. Also disclosed is a method for treating a neoplastic disease, an autoimmune disease, or a neurodegenerative disease with these compounds.

The disclosure includes compounds of Formula (A): ##STR00001##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10, R.sub.11, and R.sub.12, j, k, m, n, Y, W, W.sub.1, W.sub.2, W.sub.3, V, L, Z.sub.1, Q.sub.1, Q.sub.2, Q.sub.3, and Q.sub.4, are defined herein. Also disclosed is a method for treating a neoplastic disease, an autoimmune disease, or a neurodegenerative disease with these compounds.