KR20240096794A - Therapeutic agent for aspiration pneumonia, lung suppuration, or lung abscess - Google Patents

Abstract

[Project] This is about a treatment for respiratory infections with higher efficacy and safety.
[Solution] 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl )-8-Methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof as an active ingredient for the treatment of aspiration pneumonia, pulmonary empyema or pulmonary abscess.

Description

Treatment of aspiration pneumonia, pulmonary empyema or pulmonary abscess {THERAPEUTIC AGENT FOR ASPIRATION PNEUMONIA, LUNG SUPPURATION, OR LUNG ABSCESS}

The present invention relates to a treatment for aspiration pneumonia, pulmonary empyema, or lung abscess.

Following the development of norfloxacin, the development of quinolone carboxylic acid-based antibacterial agents called new quinolones has been carried out around the world, and currently, many new quinolone-based antibacterial agents are widely used as drugs for treating infectious diseases. Additionally, the applicant discloses a quinolone carboxylic acid derivative represented by general formula (1) (Patent Document 1).

In formula (1), R ¹ is an alkyl group of 1 to 6 carbon atoms which may be substituted by 1 or 2 or more halogen atoms, a cycloalkyl group of 3 to 6 carbon atoms which may be substituted by 1 or 2 or more halogen atoms, or a halogen atom and an amino group. An aryl group or heteroaryl group that may be substituted with 1 or 2 or more of the same or different substituents selected, R ² is a hydrogen atom, an alkyl group with 1 to 3 carbon atoms, a pharmaceutically acceptable cation, and R ³ is a hydrogen atom or halogen. Atom, hydroxyl group, amino group or alkyl group having 1 to 3 carbon atoms, R ⁴ is hydrogen atom or halogen atom, R ⁵ is fluorine atom, R ⁶ is hydrogen atom or fluorine atom, A is nitrogen atom or =CX(X represents an alkyl group with 1 to 3 carbon atoms or an alkoxy group with 1 to 3 carbon atoms which may be substituted with 1 or 2 or more halogen atoms, a hydrogen atom, a halogen atom, an amino group, a cyano group, or a halogen atom.

Additionally, in Patent Document 1, as one of the above-mentioned quinolone carboxylic acid derivatives, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6 -Fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid is disclosed. Additionally, the hydrochloride salt is disclosed in Patent Document 2.

Additionally, aspiration pneumonia is one of the respiratory infections. Aspiration pneumonia is a disease that accounts for the majority of pneumonia in the elderly and is a serious disease that is intractable, recurrent, and has a high mortality rate (Non-patent Document 1). Causes of aspiration pneumonia include anaerobic bacteria, Staphylococcus aureus, and enteric bacteria (Non-Patent Document 1), but to date, no effective treatment method for aspiration pneumonia has been established. Quinolone preparations currently on the market include levofloxacin, ciprofloxacin, pazufloxacin, moxifloxacin, sitafloxacin, and garenoxacin. For aspiration pneumonia, which is a disease of high severity, injectable preparations are mostly used in the initial treatment, but among the above-mentioned quinolone preparations, levofloxacin, ciprofloxacin, and pazufloxacin, which have injectable preparations, have insufficient antibacterial activity against anaerobic bacteria. And, its use in patients suspected of aspiration pneumonia is not recommended (Non-patent Document 2). As for oral agents, sitafloxacin, moxifloxacin, and garenoxacin are likely to be effective against anaerobic bacterial infections (Non-Patent Documents 3 to 5), but these papers have high evidence targeting aspiration pneumonia. There are no reports, and it has not been established as an effective treatment method to date.

Like aspiration pneumonia, lung abscess is an example of a respiratory infection mainly caused by anaerobic bacteria (Non-patent Document 6). There are reports confirming the therapeutic effect of moxifloxacin and pazufloxacin (Non-Patent Documents 3 to 4 and Non-Patent Document 7), but it has not been established as an effective treatment method to date.

[Prior art literature]

- Patent literature

(Patent Document 1) WO2005026147 A

(Patent Document 2) WO2013069297 A

- Non-patent literature

(Non-patent Document 1) The Journal of the Japanese Society of Internal Medicine, 99:11, November 10, 2010, p. 2746-2751.

(Non-patent Document 2) The Japanese Respiratory Society, Medical/Care-related Pneumonia Clinical Practice Guidelines, p. 23.

(Non-patent Document 3) Infection (Munich, Germany) (2008), 36(1), 23-30.

(Non-patent Document 4) Expert Review of Respiratory Medicine (2007), 1(1), 111-119.

(Non-patent Document 5) The Japanese Respiratory Society, Adult Pneumonia Clinical Practice Guidelines 2017, p. 24.

(Non-patent Document 6) Annals of The Japanese Respiratory Society, 49(9): 623-628, 2011.

(Non-patent Document 7) Nippon Kagaku Ryoho Gakkai Zasshi (1999), 47(Suppl. 1), 196-203.

The purpose of the present invention is to provide a novel therapeutic agent for respiratory infections.

The present inventor conducted research on a therapeutic agent for respiratory infections with high efficacy and safety. The present inventors have conducted intensive studies on the above problem, and 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro -1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid was found to be very effective as a treatment for aspiration pneumonia, pulmonary empyema, or pulmonary abscess. , arrived at the present invention.

The gist of the present invention is as follows.

[1] 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl) A treatment for aspiration pneumonia, pulmonary purulent disease, or pulmonary abscess containing -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof as an active ingredient.

[2] 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl) A therapeutic agent for aspiration pneumonia containing -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof as an active ingredient.

[3] 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl) A treatment for pulmonary suppuration or pulmonary abscess containing -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof as an active ingredient.

[4] The bacteria causing the above-mentioned aspiration pneumonia, pulmonary suppuration or pulmonary abscess are bacteria belonging to the genus Prevotella , bacteria belonging to the genus Peptostreptococcus , bacteria belonging to the genus Parvimonas , and peptoniphilus. The therapeutic agent according to [1], which is one or two or more types of bacteria selected from the group consisting of bacteria belonging to the genus Peptoniphilus , bacteria belonging to the genus Finegoldia , and bacteria belonging to the genus Fusobacterium .

[5] The bacteria causing the above-mentioned aspiration pneumonia are bacteria belonging to the genus Prevotella, bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Peptoniphilus, bacteria belonging to the genus Feingoldia, and bacteria belonging to the genus Fusobacterium. The therapeutic agent according to [2], which is one or two or more types of bacteria selected from the group consisting of bacteria belonging to the group.

[6] The bacteria causing the above-mentioned pulmonary purulent disease or pulmonary abscess are bacteria belonging to the genus Prevotella, bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Peptoniphilus, bacteria belonging to the genus Feingoldia, and bacteria belonging to the genus Feingoldia. The therapeutic agent according to [3], which is one or two or more types of bacteria selected from the group consisting of bacteria belonging to the genus Sobacterium.

[7] The bacteria causing the above-mentioned aspiration pneumonia, pulmonary purulent disease, or pulmonary abscess are bacteria belonging to the genus Bacteroides , bacteria belonging to the genus Prevotella, bacteria belonging to the genus Porphyromonas , and bacteria belonging to the genus Fusobacterium. Bacteria belonging to the genus Leptotrichia , bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Veillonella , bacteria belonging to the genus Tissierella , Streptococcus anzino The therapeutic agent according to [1], which is one or two or more types of bacteria selected from the group consisting of Streptococcus anginosus and bacteria belonging to the genus Actinomyces .

[8] The bacteria causing the aspiration pneumonia are 1 selected from the group consisting of bacteria belonging to the genus Bacteroides, bacteria belonging to the genus Prevotella, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Veillonella, and bacteria belonging to the genus Actinomyces. The therapeutic agent described in [2], which is a species or two or more types of bacteria.

[9] The bacteria causing the above-mentioned pulmonary purulent disease or pulmonary abscess are bacteria belonging to the genus Bacteroides, bacteria belonging to the genus Prevotella, bacteria belonging to the genus Porphyromonas, bacteria belonging to the genus Fusobacterium, bacteria belonging to the genus Leptotrichia, and Peptobacteria. One or two or more types of bacteria selected from the group consisting of bacteria belonging to the genus Streptococcus, bacteria belonging to the genus Falvimonas, bacteria belonging to the genus Veillonella, bacteria belonging to the genus Tisierella, and Streptococcus anginosus, as described in [3]. remedy.

[10] 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl) The daily dose of -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof is 7-[(3S,4S)-3-{(cyclo propylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline -Converted to 3-carboxylic acid, the therapeutic agent described in [1] is 300 mg on the start date of administration and 150 mg on the second day after administration.

[11] 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl) The daily dose of -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof is 7-[(3S,4S)-3-{(cyclo propylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline -Converted to 3-carboxylic acid, the therapeutic agent described in [2] is 300 mg on the start date of administration and 150 mg on the second day of administration and thereafter.

[12] 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl) The daily dose of -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof is 7-[(3S,4S)-3-{(cyclo propylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline -Converted to 3-carboxylic acid, the therapeutic agent described in [3] is 300 mg on the start date of administration and 150 mg on the second day of administration and thereafter.

According to the present invention, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoro Aspiration pneumonia, pulmonary empyema or pulmonary disease, including administering ethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof to a patient. It can provide treatment for abscesses.

Hereinafter, one embodiment of the present invention will be described in detail.

The therapeutic agent of this embodiment relates to a therapeutic agent for respiratory diseases, and particularly relates to a therapeutic agent for respiratory infections. More specifically, the therapeutic agent of the present embodiment is 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro- Administering 1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof to patients, including humans. It relates to a treatment for aspiration pneumonia, pulmonary empyema, or lung abscess, including:

Respiratory infection refers to an infection that occurs in any part of the respiratory tract. Additionally, the respiratory tract is a general term for organs related to breathing, and refers to the organs from the nasal vestibule to the alveoli via the nasal cavity, pharynx, larynx, trachea, bronchi, and bronchioles. In this specification, “aspiration pneumonia” is a respiratory condition that includes swelling and infection of the lungs or upper respiratory tract, and is believed to be caused by inhaling harmful substances. Patients infected with aspiration pneumonia may experience symptoms such as coughing and difficulty breathing. In this specification, a patient with aspiration pneumonia means a person who satisfies the following criteria.

A clear infiltrative shadow appears acutely on a chest X-ray or CT image.

A person has a clear misfire confirmed, repeated airway obstruction has been confirmed, a functional impairment has been confirmed in a swallowing function evaluation test, or has a comorbidity or history of a disease with the possibility of a swallowing function impairment.

It shows symptoms and inflammation that are characteristic of aspiration pneumonia.

In addition, the characteristic symptoms and inflammatory findings of aspiration pneumonia include cough, purulent phlegm, wet rales, shortness of breath, fever, positive CRP, increased white blood cells, and hypoxemia.

In this specification, “pulmonary empyema” is also referred to as a lung abscess and is a necrotic lung infection that is believed to be caused by inhalation of bacteria from the mouth or throat into the lungs. Patients infected with pulmonary purulent pneumonia may experience symptoms such as fatigue, loss of appetite, cold sweats, fever, weight loss, and cough with phlegm. In the present specification, a patient with pyogenic pulmonary disease means a person who satisfies the following criteria.

On a chest X-ray or CT image, a massive shadow or a shadow with a cavity inside (nodule shadow, mass shadow) is confirmed. (It does not matter whether there is a specular lesion due to pus retention.)

It shows symptoms and inflammation that are characteristic of pulmonary suppuration and pulmonary abscess.

In addition, symptoms and inflammatory findings characteristic of pulmonary purulent disease or pulmonary abscess include cough, purulent phlegm, wet cough, shortness of breath, fever, positive CRP, increased white blood cells, and hypoxemia.

Finding compounds that are safe and effective against anaerobic pathogens is important to effectively treat diseases such as aspiration pneumonia, pulmonary pyogenes, or pulmonary abscesses. Applicant 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)- 8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and its pharmaceutically acceptable salts were found to be effective against anaerobic pathogens, unlike other quinolone compounds. For example, injections of quinolone compounds such as levofloxacin, ciprofloxacin, or pazufloxacin are not considered suitable as a treatment for aspiration pneumonia (Non-patent Document 2).

However, Applicant claims that 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl )-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and its pharmaceutically acceptable salts were found to be effective against anaerobic pathogens and effective for the treatment of aspiration pneumonia. did.

Also, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)- 8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof can be produced, for example, according to the method described in Patent Document 1 or 2.

The anaerobic bacteria that cause aspiration pneumonia, pulmonary empyema, or pulmonary abscess include bacteria belonging to the genus Bacteroides, bacteria belonging to the genus Prevotella, bacteria belonging to the genus Porphyromonas, bacteria belonging to the genus Fusobacterium, and Leptotri. Bacteria belonging to the genus Chia, bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Veillonella, bacteria belonging to the genus Tisierella, bacteria belonging to the genus Peptoniphilus, bacteria belonging to the genus Feingoldia, and Tongseong. Anaerobic bacteria include Streptococcus anginosus, which is included in the Streptococcus genus, and bacteria belonging to the Actinomyces genus. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- Methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid exhibits high antibacterial activity against the above-mentioned anaerobic bacteria and shows a high therapeutic effect against aspiration pneumonia, pulmonary purulent disease, or pulmonary abscess. .

As causative bacteria of aspiration pneumonia, for example, bacteria belonging to the genus Prevotella, bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Peptoniphilus, bacteria belonging to the genus Feingoldia, and Fusobacterium. Examples include bacteria belonging to the genus Bacteroides, bacteria belonging to the genus Streptococcus, etc. Regarding the treatment of aspiration pneumonia, in particular, the causative bacteria of aspiration pneumonia are bacteria belonging to the genus Bacteroides, bacteria belonging to the genus Prevotella, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Veillonella, or Actinomycetes. If uniform, belonging to the genus Seth, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoro Roethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid has a high therapeutic effect.

As bacteria causing pulmonary purulent disease or pulmonary abscess, for example, bacteria belonging to the genus Prevotella, bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Peptoniphilus, bacteria belonging to the genus Feingoldia, Bacteria belonging to the genus Fusobacterium, bacteria belonging to the genus Bacteroides, and bacteria belonging to the genus Streptococcus can be mentioned.

Regarding the treatment of pulmonary pyometra or pulmonary abscess, in particular, the causative bacteria of pulmonary pyometra or pulmonary abscess are bacteria belonging to the genus Prevotella, bacteria belonging to the genus Porphinomonas, bacteria belonging to the genus Fusobacterium, and genus Leptotrichia. In the case of bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Falvimonas, bacteria belonging to the Veillonella genus, bacteria belonging to the genus Tysierella, or Streptococcus anginosus, 7-[(3S,4S)-3-{( cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydro Quinoline-3-carboxylic acid has a high therapeutic effect.

As a fungus belonging to the genus Prevotella, for example, blood. Denticola ( P. denticola ), blood. P. loescheii , p. Melaninogenica ( P. melaninogenica ), blood. intermedia ( P. intermedia ), p. Nigrescens ( P. nigrescens ), blood. Palens ( P. pallens ), p. P. buccae , p. Oris ( P. oris ), p. Buccalis ( P. buccalis ), p. Oralis ( P. oralis ), blood. Bivia ( P. bivia ), p. Disiens ( P. disiens ), p. P. pleuritidis , blood. Bergensis ( P. bergensis ), blood. Timonensis ( P. timonensis ), or blood. This includes the genus P. nanceiencis . 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the bacteria causing aspiration pneumonia are blood. Melaninogenica, p. Intermedia or blood. In the case of Bucaae, the bacteria causing pulmonary purulent disease or pulmonary abscess are blood. Melaninogenica, p. Intermedia or blood. An example is Oralis. Examples of bacteria belonging to the genus Peptostreptococcus include P.anaerobius or P.stomatis.

Bacteria belonging to the genus P. falvimonas, for example, blood. Micra ( P. micra ) can be mentioned. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the bacteria causing aspiration pneumonia, pulmonary pyometosis or pulmonary abscess are blood. An example would be Mikra. Bacteria belonging to the genus Peptoniphilus, for example, Peptoniphilus asaccharolyticus , Peptoniphilus ivoryi, Peptoniphilus lacrimalis , or Peptoniphilus Examples include Peptoniphilus harei . 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the bacteria causing aspiration pneumonia, pulmonary purulent inflammation or pulmonary abscess is Peptoniphilus. An example is Asacharoliticus.

Examples of bacteria belonging to the genus Finegoldia include Finegoldia magna . 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the bacteria causing aspiration pneumonia, pulmonary purulent inflammation or pulmonary abscess is Pinegodia magna. One case can be given.

As a fungus belonging to the genus Fusobacterium, for example, F. Necrophorum ( F. necrophorum ), F. Nucleatum ( F. nucleatum ), f. Mortiferum ( F. mortiferum ) or F. Examples include barium ( F. varium ). 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the causative bacteria of pulmonary purulent disease or pulmonary abscess are F. Nucleatum or F. An example would be Necrophorum. As a fungus belonging to the genus Bacteroides, for example, B. B. fragilis, B. B. thetaiotaomicron , B. B. vulgatus , B. B. ovatus , B. Uniformis ( B. uniformis ), B. B. eggerthii , B. Nordii ( B. nordii ), B. Salyersae ( B. salyersae ), or B. Massiliensis ( B. massiliensis ) can be mentioned. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the bacteria causing pulmonary suppuration or pulmonary abscess are non. An example is Fragilis.

Bacteria belonging to the genus Porphyromonas, for example, blood. P. gingivalis , p. Endodontalis ( P. endodontalis ), p. Asaccharolytica ( P. asaccharolytica ), p. Levii ( P. levii ) or P. Examples include P. uenonis . 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the bacteria causing pulmonary suppuration or pulmonary abscess are blood. gingivalis or blood. An example is endodontalis.

Bacteria belonging to the genus Leptotrichia, for example, L. Buccalis ( L. buccalis ), L. Hofstadii ( L. hofstadii ), L. L. hongkongensis, L. L. shahii, L. Goodfellowii ( L. goodfellowii ), L. Trevisanii ( L. trevisanii ) or L. L. wadei may be mentioned. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the bacteria causing pulmonary suppuration or pulmonary abscess are L. An example would be Bukalis. Bacteria belonging to the genus Veillonella, for example, V. V. parvula, V. Atypica ( V. atypica ) or V. Examples include Montpelliensis ( V. montpelliensis ).

Bacteria belonging to the genus T. sierella, for example, T. T. creatinini, T. Creatinophila ( T. creatinophila ), or T. Examples include T. praeacuta . 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the bacteria causing pulmonary suppuration or pulmonary abscess are T. An example would be Creatinini.

Bacteria belonging to Streptococcus anginosus, for example, S. S. intermedius or S. Examples include Constellatus ( S. constellatus ). 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the bacteria causing pulmonary suppuration or pulmonary abscess are S. Intermedius or S. An example would be Constellatus.

As a fungus belonging to the genus Actinomyces, for example, A. A. europaeus, A. A. georgiae , A. A. gerencseriae , A. A. graevenitzii, A. A. israelii, A. A. meyeri, A. A. naeslundii , A. A. neuii, A. A. odontolyticus, a. A. radicidentis, A. A. radingae, a. A. turicensis , A. A. urogenitalis , A. Examples include A. viscocus or Actinomyces sp. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- From the viewpoint of the therapeutic effect of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, more preferably, the bacteria causing aspiration pneumonia are A. An example is Odontolyticus.

In this specification, the concept of pathogenic bacteria also includes bacteria that have acquired drug resistance. Drug resistance refers to a phenomenon in which an organism has resistance to a drug and the drug does not work or becomes difficult to listen to. Examples of drug resistance include penicillin resistance, cephalosporin resistance, carbapenem resistance, aminoglycoside resistance, macrolide resistance, lincomycin resistance, trimethoprim-sulfamethoxazole resistance, tetracycline resistance, metronidazole resistance, and glycopeptide resistance. , oxazolidinone resistance, daptomycin resistance, or quinolone resistance.

In the above-mentioned pharmaceutical composition, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoro Pharmaceutically acceptable additives contained with loethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid include, for example, excipients, lubricants, binders, disintegrants, Stabilizers, flavoring agents, and diluents may be included. These additives are not particularly limited as long as they can be used in the production of pharmaceutical preparations, and for example, those described in the literature [Pharmaceutical Additives Dictionary "International Pharmaceutical Excipients Council Japan, Yakuji Nippo (2007)"] can be used appropriately.

The therapeutic agent of this embodiment can be administered to subjects such as humans by applying a form and administration route well known in the pharmaceutical field, for example, powder, tablet, capsule, microgranule, granule, syrup, injection, It can be administered orally or parenterally as preparations such as ophthalmic solutions, aqueous nasal drops, aqueous ear drops, and inhalation liquids. That is, the therapeutic agent of the present embodiment can be prepared by mixing the active ingredient with a physiologically acceptable carrier, excipient, binder, diluent, etc., into a formulation as exemplified above.

In the therapeutic agent of the present embodiment, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluo is used in terms of reducing side effects, preparing a small formulation for easy administration, and preventing the emergence of resistant bacteria. Lopyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutical The minimum amount of salt allowed per day is preferably 10 mg or more, 20 mg or more, 50 mg or more, 100 mg or more, 125 mg or more, or 150 mg or more. Additionally, the maximum daily dosage is preferably 300 mg or less, 250 mg or less, 200 mg or less, or 175 mg or less. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- The daily dosage of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof may be, for example, 10 mg or more and 300 mg or less. Preferably 20 mg or more and 250 mg or less, more preferably 50 mg or more and 200 mg or less, further preferably 100 mg or more and 200 mg or less, further preferably 125 mg or more and 175 mg or less, particularly preferably 150 mg or more. ㎎ may be mentioned. In addition, the above daily dosage is 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1- When using a pharmaceutically acceptable salt of (2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, the value converted to the free form is used. The dosage for one day may be administered once or in two or three divided doses, but administration once a day is preferable. Additionally, if the effect is insufficient, twice the daily dose may be used.

Additionally, in order to quickly reach the target blood concentration, it is preferable to perform loading administration. Loading administration refers to an administration design to reach the target blood concentration early by increasing the daily dosage or increasing the number of daily administrations in the initial stage of administration. The initial period of administration means the 1st to 3rd day from the start of administration, preferably the 1st to 2nd day from the start of administration, and more preferably the 1st day from the start of administration. Additionally, as an increase in the daily dosage, preferably twice the daily dosage is used.

When performing loading administration, it is preferable to use twice the daily dosage on the first day of administration. More preferred, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl) The daily dose of -8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof, in terms of vitreous body, is 300 mg on the start day of administration, and administration After the second day, it is 150 mg.

7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- The dosage of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid salt is preferably 300 mg on the starting day of administration and 150 mg on the second day of administration or later. Here, the corresponding dosage is 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2 -Fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid is the value converted to free form.

7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- The pharmaceutically acceptable salt of methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid may be a pharmaceutically acceptable salt. Examples of pharmaceutically acceptable salts include salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid; Salts with organic acids such as maleic acid, fumaric acid, succinic acid, malic acid, malonic acid, methanesulfonic acid, toluenesulfonic acid, benzenesulfonic acid, lactic acid, oxalic acid, acetic acid, trifluoroacetic acid, and tartaric acid; Alternatively, salts with metals such as sodium, potassium, magnesium, calcium, aluminum, cesium, chromium, cobalt, copper, iron, zinc, platinum, and silver may be mentioned. Among these, hydrochloride is particularly preferred.

In addition, “free form” refers to 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidine-1, which is not in the form of any salt, co-crystal, or hydrate. -1]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, and the molecular formula is C ₂₁ H ₂₄ F ₃ N ₃ O ₄ , a compound with a molecular weight of 439.44.

The therapeutic agent of this embodiment is 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2- Fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof may be used alone as the active ingredient. Alternatively, the therapeutic agent of the present embodiment is 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-( 2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof, and other compounds acting as active ingredients and/or pharmaceutical agents It may be composed as a pharmaceutical composition containing acceptable additives.

The pharmaceutical composition may contain one or more compounds as other compounds acting as active ingredients and/or pharmaceutically acceptable additives. The pharmaceutical composition is, for example, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-( 2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof, and one of other compounds and additives that act as active ingredients It is prepared by mixing the above.

As described above, according to the present embodiment, it is possible to provide technology regarding a therapeutic agent with high therapeutic effect and safety for aspiration pneumonia, pulmonary empyema, or pulmonary abscess. By using an appropriate composition described in the present specification, it is possible to obtain a sufficient therapeutic effect while reducing side effects and reducing the frequency of appearance of resistant bacteria, even when a small dosage is used.

(Example)

The present invention will be described in more detail below by way of examples, but the scope of the present invention is not limited by these examples.

According to the method disclosed in International Publication No. 2016/195014, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6 -150 mg injection of fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (hereinafter also referred to as investigational new drug A) manufactured.

In addition, “150 mg” of 150 mg injection means 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1 The weight of -(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid salt is expressed in terms of free form. When preparing an injection, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoro 162.5 mg (equivalent to free form: 150 mg) of ethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate is used.

(Test Example 1) Aspiration pneumonia

The experimental new drug A was administered intravenously for 7 to 14 days to 13 subjects suspected of having aspiration pneumonia who met the following criteria.

In patients 16 years of age or older, a clear infiltrative shadow appears acutely on a chest X-ray or CT image taken within 48 hours before the start of administration.

A clear misconception is confirmed, and the patient has or has a history of airway obstruction, impaired swallowing function, or a disease with the possibility of impaired swallowing function.

It shows symptoms and inflammation that are characteristic of aspiration pneumonia.

On the first day of administration, use two investigational new drugs A (300 mg/day), and on the second day of administration, use one investigational new drug A (150 mg/day), and then maintain the same dosage (150 mg/day). did. The injections were administered by intravenous drip over a period of approximately 1 hour.

(Test Example 2) Pulmonary suppuration or lung abscess

The experimental new drug A was administered intravenously for 7 to 14 days to 11 subjects suspected of having pulmonary pyometra or pulmonary abscess that met the following criteria.

For those 16 years of age or older, check for lump-shaped shadows or shadows with internal cavities (nodule shadows, mass shadows) on chest X-rays or CT images taken within 48 hours before the start of administration. Additionally, the presence or absence of specular lesions due to accumulation of pus is irrelevant.

It shows symptoms and inflammation that are characteristic of pulmonary suppuration and pulmonary abscess.

On the first day of administration, use two investigational new drugs A (300 mg/day), and on the second day of administration, use one investigational new drug A (150 mg/day), and then maintain the same dosage (150 mg/day). did. The injections were administered by intravenous drip over a period of approximately 1 hour. The clinical effects of Test Examples 1 and 2 are described in the literature [Clinical evaluation method of new antibacterial drugs in respiratory infections (2nd edition), Japanese Journal of Chemotherapy. 2012; 60(1): 30-45. 9)], the following standards were set and judgment was made based on the criteria for determining the clinical effect of pneumonia. In addition, the main evaluation item was the effectiveness rate at the end or discontinuation of administration of investigational new drug A.

In this specification, the end of administration refers to the evaluation date on the day following the day on which administration of investigational new drug A was completed. In addition, the time of discontinuation refers to the date of evaluation conducted within 3 days from the date of final administration of investigational new drug A or the date of decision to discontinue. Additionally, “at the end or stop of administration” is expressed as End of Treatment (EOT). Additionally, CRP is an abbreviation for C-reactive protein, and is one of the acute phase reactive substances produced in a short period of time in response to various types of inflammation. In bacterial infections such as pneumonia, it rises within a few hours and quickly decreases as the inflammation subsides, so it is a helpful indicator for observing the treatment effect.

Early evaluation of efficacy and at end of treatment (EOT)

The early drug efficacy evaluation was judged in three levels according to Table 1 after 3 days of administration: “Early therapeutic effect,” “Early treatment effect,” and “No judgment.”

The definition of “early treatment effect” was defined as a case in which significant improvement was confirmed 3 days after administration (irrelevant with the end or continuation of administration after 4 days). In addition, for cases in which the CRP value or chest It was judged that “early treatment is effective.”

If CRP or chest The doctor in charge of the clinical trial made an appropriate decision, including replacing it with drug administration. Additionally, before initiating appropriate alternative antibacterial treatment, samples for microbiological evaluation were collected.

In addition, when the discontinuation date was the start date of administration (day 0) or the second day of administration (day 1), determination of early drug efficacy evaluation was unnecessary. After the third day (day 2) of administration, judgment was made using the test results at the time of discontinuation.

At the end of treatment (EOT), the clinical effect at the end or discontinuation of administration was judged into three levels: "effective", "invalid", and "unable to judge" according to Table 1. If administration was stopped the next day or later, the clinical effect at the end of administration was judged, and the clinical effect at the time of discontinuation was determined as unnecessary.

In addition, if treatment was stopped or changed to alternative antibacterial treatment after completion of treatment with the investigational new drug, it was judged to be “invalid.” However, if it is judged to be “effective” according to the judgment criteria in Table 1 at the end of treatment (EOT), this does not apply even if the treatment is changed to an alternative antibacterial drug. In addition, when changing to alternative antibacterial treatment, the prescribed examination, examination, and judgment at the end of treatment were conducted before the change in principle.

Criteria for early drug efficacy evaluation and completion of treatment
Early treatment effective/effective
a. below is satisfied, and b. or c. is met and there is no deterioration in the remaining items.
a. Loss or improvement of symptoms and findings of the original disease
It is diagnosed as fever, cough, sputum (amount, appearance), shortness of breath, chest pain, and chest pain.
Improvement in one or more conditions or findings.
In cases of fever at the start of the test (at the time of mixing), improvement of fever is essential.
If the body temperature decreases from the temperature at the start of the test (at the time of mixing), it is considered an improvement in fever even if it is 37.0℃ or higher.

b. All abnormal findings in chest burns disappear or improve from the worst.
Judgment is made based on the magnification and density of the shading.

c. Disappearance or improvement of inflammatory findings
Indicates either an improvement in the white blood cell count below 9,000/㎣ or a decrease in CRP from the highest level, with no items worsening. Additionally, with respect to the white blood cell count, if the increase is within the normal range as determined by a clinical examination and measurement institution, it is not judged to be a “deterioration.”

No/invalid early treatment effect
If the above conditions of “early treatment is effective” or “effective” are not shown



unable to decide
If any of the following criteria is met:
a. If there is no visit to the hospital at the end of administration, or if information on the condition and findings is lacking

b. When there is a clear reason other than the original disease for the worsening of body temperature, white blood cells, and CRP.

The results of early drug efficacy evaluation and completion of treatment in Test Examples 1 and 2 are shown in Tables 2 and 3.

Early drug efficacy evaluation clinical effect effective rate available invalidity unable to decide Test example 1 12 One 0 92% Test example 2 9 2 0 82%

At the end of treatment clinical effect effective rate available invalidity unable to decide Test example 1 12 0 One 100% Test example 2 10 One 0 91%

Meanwhile, the effective rate is a value obtained by the following equation. Effective rate = (Number of subjects determined as “effective” ÷ Number of subjects determined as “effective” or “invalid”) × 100 (%)

From Table 2 and Table 3, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2- Fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof has a high therapeutic effect on aspiration pneumonia, pulmonary purulent inflammation or pulmonary abscess. You can see that it is effective. In particular, the effectiveness rate at the end of treatment is remarkably high, at 100% for aspiration pneumonia and 91% for pulmonary purulent disease or lung abscess.

The microbiological effects of each causative bacteria in Test Examples 1 and 2 are shown in Tables 4 and 5.

Microbiological effects by pathogen (aspiration pneumonia)
bacterium
number of cases result disappearance subsistence anaerobic bacteria 19 17 2 Actinomyces genus no way. Odontolyticus One One 0 Falvimonas genus blood. micra One One 0 Veilonella genus Veillonella spp. 7 5 2 Bacteroides genus Bacteroides spp. 2 2 0
Prevotella genus Prevotella species 6 6 0 blood. Bukaae One One 0 blood. Intermedia One One 0

Microbiological effects of each pathogen (pulmonary purulent disease, pulmonary abscess)
bacterium
number of cases result disappearance subsistence anaerobic bacteria 16 15 One Falvimonas genus blood. micra 2 2 0 Veilonella genus Veillonella spp. 2 2 0 Bacteroides genus rain. fragilis One One 0 Fusobacterium genus F. Necrophorum One One 0 F. nucleatum 4 4 0 Leptotrichia genus Leptotrichia bucalis One One 0 Porphyromonas genus blood. Gingivalis One One 0
Prevotella genus Prevotella species One One 0 blood. Intermedia One 0 One blood. Melaninogenica One One 0 blood. Oralis One One 0

From Table 4 and Table 5, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2- Fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof is effective against the causative agent of aspiration pneumonia, pulmonary pyometra, or pulmonary abscess. , it can be seen that it has a high antibacterial effect.

According to this embodiment, it is possible to provide a therapeutic agent for aspiration pneumonia, pulmonary empyema, or pulmonary abscess, and is industrially useful.

Claims (9)

7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- A treatment for aspiration pneumonia, pulmonary empyema or pulmonary abscess containing methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof as an active ingredient,
The bacteria causing the above-mentioned aspiration pneumonia, pulmonary pyolosis or pulmonary abscess is one selected from the group consisting of bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Peptoniphilus, and bacteria belonging to the genus Feingoldia. A therapeutic agent that is a species or two or more types of fungi. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- A treatment for aspiration pneumonia containing methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof as an active ingredient,
The bacteria causing the aspiration pneumonia are one or two or more species selected from the group consisting of bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Peptoniphilus, and bacteria belonging to the genus Feingoldia, remedy. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- A treatment for pulmonary suppuration or pulmonary abscess containing methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof as an active ingredient,
The bacteria causing the pulmonary purulent disease or pulmonary abscess are one or two species selected from the group consisting of bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Peptoniphilus, and bacteria belonging to the genus Feingoldia. A cure for the above bacteria. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- A treatment for aspiration pneumonia, pulmonary empyema or pulmonary abscess containing methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof as an active ingredient,
The bacteria causing the above-mentioned aspiration pneumonia, pulmonary purulent disease or pulmonary abscess are bacteria belonging to the genus Porphyromonas, bacteria belonging to the genus Leptotrichia, bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Veillonella, The therapeutic agent, which is one or two or more types of bacteria selected from the group consisting of bacteria belonging to the genus Tisierella, Streptococcus anginosus group, and bacteria belonging to the genus Actinomyces. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- A treatment for aspiration pneumonia containing methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof as an active ingredient, wherein the bacteria causing the aspiration pneumonia are: The therapeutic agent, which is one or two or more types of bacteria selected from the group consisting of bacteria belonging to the genus Monas, bacteria belonging to the genus Veillonella, and genus Actinomyces. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8- A treatment for pulmonary suppuration or pulmonary abscess containing methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof as an active ingredient,
The bacteria causing the pulmonary purulent disease or pulmonary abscess are bacteria belonging to the genus Porphyromonas, bacteria belonging to the genus Leptotrichia, bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Palvimonas, bacteria belonging to the genus Veillonella, and bacteria belonging to the genus Tisierella. The therapeutic agent is one or two or more types of bacteria selected from the group consisting of bacteria and Streptococcus anginosus. The method of claim 1 or 4, wherein 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1- The daily dose of (2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof is 7-[(3S,4S)- 3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1, The above therapeutic agent, converted to 4-dihydroquinoline-3-carboxylic acid, is 300 mg on the start date of administration and 150 mg on the second day of administration and thereafter. The method of claim 2 or 5, wherein 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1- The daily dose of (2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof is 7-[(3S,4S)- 3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1, The above therapeutic agent, converted to 4-dihydroquinoline-3-carboxylic acid, is 300 mg on the start date of administration and 150 mg on the second day of administration and thereafter. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1- according to claim 3 or 6 The daily dose of (2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof is 7-[(3S,4S)- 3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1, The above therapeutic agent, converted to 4-dihydroquinoline-3-carboxylic acid, is 300 mg on the start date of administration and 150 mg on the second day of administration and thereafter.