JP2001097863A - Use of fluoroquinolone compound against anaerobic pathogenic bacteria - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for using a more potent antibacterial compound against bacterial pathogen. SOLUTION: This method for using a more potent antibacterial compound is to control the metabolism of anaerobic pathogenic bacteria and comprises bringing the anaerobic pathogenic bacteria into contact with a composition containing gemifloxacin compound or its antibacterially effective derivative in their antibacterially effective amount. As the anaerobic bacteria, Peptostreptococcus anaerobius, Peptostreptococcus asaccharolyticus, or the like, are cited.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

FIELD OF THE INVENTION The present invention relates, in part, to the use of quinolone antibiotics, particularly gemifloxacin compounds, with anaerobic bacteria such as Peptostreptococcus.
Anerobius (Peptostreptococcus anaerobius), Peptostreptococcus assacarolicus (Peptostreptococcus anaerobius)
ostreptococcus asaccharolyticus), Peptostreptococcus indolcus
icus), Peptostreptococcus magnus (Peptos
treptococcus magnus), peptostreptococcus
Micros (Peptostreptococcus micros), Peptostreptococcus prevotii (Peptostreptococcus pre
votii), Staphylococcus saccharolyticus (S
taphylococcus saccharolyticus), Atopobium parvulus, Streptococcus constellatus,
Streptococcus intermedius
cus intermedius, Gemella morbirolum
orbillorum), Clostridium clostridioforme, Clostridium difficile, Clostridium perfringens
rfringens), Clostridium septicum (Clostri)
dium septicum), Clostridium sordellii (Clo)
stridium sordellii), Clostridium ramosum, propionibacterium
Acnes (Propionibacterium acnes), Propionibacterium granulosum
ulosum), Eubacterium rentum (Eubacterium)
lentum), Actinomyces odontricis (Acti)
nomyces odontolyticus), Bifidobacterium adolescentis,
Bifidobacterium bifidum
bifidum), Bifidob
acterium breve), Bifidobacterium longum, Bifidobacterium longum
Pseudolongum (Bifidobacterium pseudolongum),
Lactobacillus, Lactobacillus
Brevis subspecies Brevis (Lactobacillus brevis subsp.
Brevis), Lactobacillus casei subspecies casei (Lactob)
casei), Lactobacillus fermentum, Lactobacillus plantarum, Lactobacillus reuteri,
Lactobacillus salivarium subspecies salibarium (Lact
obacillus salivarius subsp. salivarius, Bacteroides fragilis, Bacteroides vulgatus, Bacteroides distasoni
s), Bacteroides ovatu
s), Bacteroides thetaiotaomicron (Bacte
roides thetaiotaomicron), Bacteroides uniformis (Bacteroides uniformis), Bacteroides eggerthii (Bacteroides eggerthii), Bacteroides ureolyticus (Bacteroides ureolyticus),
Campylobacter gracil
is), Sutterella wadsworthensis (Sutterella wad)
sworthensis), Prevotella bivi
a), Prevotella buccae, Prevotella corporis, Prevotella heparinolytic
a), Prevotella inte
rmedia), Prevotella melaninogenia (Prevotella m
elaninogenica), Prevotella oralis (Prevotella)
oralis), Prevotella oris,
Porphyromonas
asaccharolytica), Porphylomonas gingivalis, Fusobacterium nucleatum, Fusobacterium varium, Fusobacterium necropho
rum), biophila wadsworthia (Bilophilla wads)
worthia), Desulfomonas pi
gra), Capnocytofac Ochracea (Capnocyto)
phaga ochracea), Bayonella parvula (Veillone)
llaparvula), Veillonella
dispar), Peptostreptococcus anerobius, Peptostreptococcus anaerobius, Peptostreptococc
us asccharolyticus), Peptostreptococcus magnus, Peptostreptococcus micros (Peptostreptococcus micro)
s), Propionibacterium acnes
terium acnes), Actinomyces sp.
p.), Clostridium difficile
difficile), Clostridium perfringens, Bacteroides distasonis, Bacteroides fragilis, Bacteroides thetaiotomicron
aomicron), Bacteroides Uniformis (Bacter)
oides uniformis), B.fragilis
Microbial communities (B. caccae, B. eggerthii, B. ovatu)
s)), imipenem-resistant microorganisms of the B. fragilis group (B. disistasonis, B. fragilis), Prevotella vivia (Prevotella)
bivia), Prevotella Intermedia (Prevotella)
intermedia), other Prevotella species, Porphyromonas species, Fusobacterium nucleatum and Bayonella species, especially newly identified methods used to antagonize Gram-positive anaerobic bacteria.

[0002]

BACKGROUND OF THE INVENTION Quinolones have been found to be effective at various rates against a range of bacterial pathogens. However, the disease caused by these pathogens is on the rise, and there is a need for more potent antimicrobial compounds than existing quinolones. Gemifloxacin mesylate (SB-
265805) is a novel fluoroquinolone useful as a potent antimicrobial. Gemifloxacin compounds are described in PCT Patent Application PCT / KR98 / 00051 (P
CT International Publication No. WO 98/42705). Patent application EP688872 discloses a (R, S) -7- (3-aminomethyl-4-methoxyiminopyrrolidin-1-yl) -1-cyclopropyl-6 of formula I
-Fluoro-4-oxo-1,4-dihydro-1,8-
Novel quinoline (naphthyridine) carboxylic acid derivatives, including naphthyridine-3-carboxylic acid anhydrides, are disclosed.

[0003]

Embedded image I

[0004] PCT / KR98 / 00051 is (R,
S) -7- (3-Aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl) -1-cyclopropyl-
6-fluoro-4-oxo-1,4-dihydro-1,8
-Naphthyridine-3-carboxylic acid methanesulfonate and hydrates thereof, including sesquihydrate. The present specification describes significant findings obtained with gemifloxacin compounds that antagonize anaerobic pathogens,
As described in more detail herein, provides the finding that the activity of the gemifloxacin compound used was superior to some quinolones. Gemifloxacin compounds treat the clinical signs elicited by a range of anaerobic pathogens, including bacteria that are resistant to conventional oral treatments, thereby meeting an unmet medical need. It is a valuable compound.

[0005]

SUMMARY OF THE INVENTION It is an object of the present invention to contact an anaerobic pathogen with an antimicrobial effective amount of a composition comprising a quinolone, especially a gemifloxacin compound or an antimicrobial effective derivative thereof. And a method of controlling the metabolism of anaerobic pathogens. A further object of the invention is
The anaerobic pathogen is Peptostreptococcus anerobius, Peptostreptococcus assaccharolyticus, Peptostreptococcus indolicus, Peptostreptococcus magnus, Peptostreptococcus micros, Peptstreptococcus prebotii, Staphylococcus・ Saccharolyticus, Atopodium parvulus, Streptococcus constellatus, Streptococcus intermedius,
Gemera morbirolum, Clostridium clostridiiforme, Clostridium difficile, Clostridium perfringens, Clostridium septicum, Clostridium sordellii, Clostridium lamousam, Propionibacterium
Acnes, Propionibacterium granulosum,
Eubacterium lentum, Actinomyces odontricis, Bifidobacterium adressentis, Bifidobacterium bifidum, Bifidobacterium humve, Bifidobacterium longum, Bifidobacterium pseudolongum, Lactobacillus, Lactobacillus brevis subsp. Brevis, Lactobacillus casei subsp. Casei, Lactobacillus fermentum, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus salivaryum subsp. Overthes, Bacteroides Seetaiotaomicron, Bacteroides Uniformis, Bacteroide · Egashii, Bacteroides Ureorichikasu, Campylobacter gracilis, Sutterera-Wazuwasenshisu, Prevotella Bibia, Prevotella Bukke, Prevotella Koruborisu, Prevotella
Heparinolytica, Prevotella intermedia, Prevotella melaninogenia, Prevotella oralis, Prevotella oris, Porphyromonas assaccharolytica, Porphyromonas gingivalis, Fusobacterium nucleatum, Fusobacterium barium, Fusobacterium necroforum, Biophila wars・ Pigra, Chapnocytofag okrasea, Bayonella parvula, Bayonela dispar, Peptostreptococcus anerobius, Puptostreptococcus assaccharolyticus, Peptostreptococcus magnus, Peptostreptococcus micros, Propionibacterium・
Acnes, Actinomyces species, Clostridium difficile, Clostridium perfringens,
Bacteroides distasonis, Bacteroides fragilis, Bacteroides thetaiotaomicron,
Bacteroides uniformis, B. fragilis group microorganisms (Bi Kakke, B. Egersii, B. oververtus), imipenem-resistant B. fragilis group microorganisms (B. distasonnis, B. fragilis), Prevotella vivia, Prevotella intermedia, etc. Prevotella, Porphyromonas, Fusobacterium
A method selected from the group consisting of Gram-positive and Gram-negative anaerobic bacteria, including Nucleatum and Bayonella species.

Also, according to the present invention, a mammal suspected of having or being at risk of being infected with an anaerobic pathogen by an antibacterial effective amount of a composition comprising a quinolone, particularly a gemifloxacin compound. And a method for treating or preventing bacterial infections caused by anaerobic pathogens. Preferred methods are provided wherein modulation of metabolism inhibits the growth of or kills the bacterium. Further preferred methods are provided wherein contacting the bacterium comprises an additional step of introducing the composition into a mammal, especially a human. According to the present invention, the bacterium is a Peptostreptococcus
Anerobius, Peptostreptococcus athacarolicus, Peptstreptococcus indolicus, Peptstreptococcus magnus, Peptstreptococcus micros, Peptstreptococcus micros
Prevotii, Staphylococcus saccharolyticus, Atopodium parvulus, Streptococcus
Consteratas, Streptococcus intermedius, Gemera morbirolum, Clostridium clostridiiforme, Clostridium difficile, Clostridium perfringens, Clostridium septicum, Clostridium sordellii, Clostridium ramosam, Propionibacterium acnes, Propionibacterium granulosaum, Eubacterium rentum, Actinomyces odontricis, Bifidobacterium adressentis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Bi Fidobacterium pseudolongum, Lactobacillus, Lactobacillus brevis subspecies Brevis, Lactobacillus L. casei subsp. Casei, Lactobacillus fermentum, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus salivarium subsp. -Uniformis, Bacteroides Egersii, Bacteroides ureoliticus, Campylobacter grasilis, Suterera wadsworthensis, Prevoterra vivia, Prevoterra bucce, Prevoterra corvolis, Prevoterra heparinolytica, Prevoterra intermedia, Prevoterra melanovorenia, Prevoterra melanenoterrania Oris, Porf Lomonas assaccharolytica, Porphyromonas gingivalis, Fusobacterium nucleatum, Fusobacterium barium, Fusobacterium necroforum, Biophila wadsworthia, Deslohomonas pigra, Chapnocytofag okrasea, Bayonela parbula, Bayoneras disparco Anerobius, P. streptococcus assaccharolyticus, P. streptococcus magnus, P. streptococcus micros, Propionibacterium acnes, Actinomyces sp., Clostridium difficile, Clostridium perfringens, Bacteroides distasonis , Bacteroides fragilis, Bacteroides Sitaiotaomi Clon, Bacteroides uniformis, B. fragilis-group microorganisms (Bi-Kakke, B. Egersii, B. ovatus), imipenem-resistant B. fragilis group microorganisms (B. distantasonis, B. fragilis), Prevotella vivia, Prevotella intermedia , Including other Prevotella species, Porphyromonas species, Fusobacterium nucleatum and Bayonella species,
Further preferred methods are provided which are selected from the group consisting of Gram positive and Gram negative anaerobic bacteria. Various changes and modifications within the spirit and scope of the disclosed invention are
It will be readily apparent to one of ordinary skill in the art from reading the following description and from reading the other parts of the present disclosure.

[0007]

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to
In particular, there is provided a method of using a composition comprising a gemifloxacin compound that antagonizes an anaerobic pathogen. As used herein, the term "gemifloxacin compound" refers to the PCT application PCT / KR98 / 0005.
1 (International Publication Number WO 98/42705 (Jan. 1998)
Published on 01 January)) or patent application EP 68877
2 means the compounds having antimicrobial activity described in these applications, and these applications are hereby incorporated by reference.

The present invention is based, in part, on the results of an assay evaluating the comparative activity of gemifloxacin, which antagonizes various anaerobic pathogens. The purpose of these assays was to determine the in vitro activity of gemifloxacin, which antagonizes various anaerobic bacteria, using trovafloxacin, sparfloxacin, ciprofloxacin (ci
profloxacin and imipenem
It was to be measured in comparison with in vitro activity. Gemifloxacin (SB-265805), a potent new in vivo activity of fluoroquinolones, combines trovafloxacin, sparfloxacin, ciprofloxacin and imipenem with 68 in vitro activities. Comparisons were made against an anaerobic control strain and 491 current clinical isolates. Brucella supplemented with 5% hemolytic sheep blood
MIC was measured by NCCLS recommended agar dilution method using HK agar. Gemifloxacin shows greater activity against control strains than sparfloxacin and ciprofloxacin. Gemifloxacin is more active than trovafloxacin against Gram-positive pathogens, but less active than trovafloxacin against Gram-negative pathogens. For clinical isolates, the order of activity for Bacteroides sp., Prevotella vivia and other Prevotella sp. Was trovafloxacin> gemifloxacin ≒ sparfloxacin> ciprofloxacin. The MIC ₉₀ values of gemifloxacin, trovafloxacin, sparfloxacin and ciprofloxacin against these gram-negative pathogens are:
8-32 μg / ml, 1-8 μg / ml, 4-32 μg
/ Ml and 32-256 μg / ml. However, gemifloxacin shows strong activity against other gram-negative pathogens (Prevotella intermedia, Porphyromonas sp. And Fusobacterium nucleatum), and its MIC ₉₀ is 0.125-0.5 μg / m 2.
l. Gemifloxacin is the most active quinolone tested against almost all anaerobic and gram-positive pathogens. MIC ₉₀ against these isolates of gemifloxacin (excluding Peptostreptococcus magnus and Clostridium difficile)
Is 0.125-2 μg / ml. Gemifloxacin is not very active against C. difficile.
Cross resistance is observed between quinolones. These results indicate that gemifloxacin is not limited to activity against gram-negative anaerobic bacteria, but has potential clinical applications in the treatment of gram-positive anaerobic infections.

Gemifloxacin (SB-26580)
5) is a novel broad-area fluoronaphthyridone carboxylic acid having a pyrrolidine substituent. This compound is reported to have strong activity against gram-positive and gram-negative anaerobic pathogens ^1,2. Conversely, the antimicrobial activity of gemifloxacin against anaerobic pathogens is poorly known. This study compares the in vitro activity of gemifloxacin against various anaerobic bacteria with the activities of trovafloxacin, sparfloxacin, ciprofloxacin and imipenem. Of the anaerobic pathogens, a total of 68 Gram-positive and negative control strains and several difficult-to-handle microaerobic anaerobic bacteria were tested. In addition, 491 isolated between 1994 and 1997
Species clinical strains were also tested. In this study, a strain of Propionibacterium acnes, mainly isolated from purulent specimens, was used. Gemifloxacin, trovafloxacin, sparfloxacin, ciprofloxacin and imipenem were used.

The MIC was measured using the agar dilution method. 5
Brucella HK agar (Mokuto, Tokyo, Japan) supplemented with% hemolytic sheep blood was used as the test medium. 1
0 ⁵ CFU / plated test strain of interest, in an anaerobic chamber _{(82% N 2, 10%} CO 2, 8% H 2), and 48 hours of incubation at 37 ° C.. Bacteroides fragilis ATCC 25285 and GAI as control strains
5562 was used. The MIC data is shown in Table 1-3. Overall, gemifloxacin shows more activity than sparfloxacin and ciprofloxacin.
Gemifloxacin is more active than trovafloxacin against most Gram-positive and several Gram-negative pathogens, but Bacteroides and Prevotella species (excluding Prevotella intermedia)
Is less active than trovafloxacin.
Bacteroides species, Prevotella vivia and Clostridium difficile are less sensitive to gemifloxacin. Gemifloxacin shows strong activity against other Gram-positive and Gram-negative anaerobic bacteria. The results show that gemifloxacin has clinical potential for treating Gram-positive anaerobic infections.

Antimicrobial activity of gemifloxacin and other drugs against Gram-positive and facultative anaerobic pathogens

[Table 1]

Antimicrobial activity of gemifloxacin and other drugs against gram-negative and facultative anaerobic pathogens

[Table 2]

In vitro activity of gemifloxacin and other drugs on clinical isolates of anaerobic pathogens

[Table 3]

[Table 4]

All studies were performed using standard standard techniques well known to those skilled in the art, unless otherwise specified.
Parts or amounts given in the following examples are by weight unless otherwise indicated. The present invention provides a method for regulating the metabolism of anaerobic pathogens. One of ordinary skill in the art can readily select patients infected or suspected of being infected with anaerobic pathogens or these microorganisms and practice the methods of the present invention. Alternatively, a bacterium useful in the method of the invention may be a bacterium described herein. The contacting step in the method of the present invention can be performed in many ways that will be apparent to those skilled in the art. However, it is preferred that the contacting step provides a composition comprising the gemifloxacin compound to a human patient in need of such a composition, or directly to bacteria in a culture medium or buffer.

For example, when contacting a human patient or contacting the bacterium in a human patient or in vitro, a composition, preferably a pharmaceutical composition, comprising a quinolone, especially a gemifloxacin compound, is used. For example, it may be administered in any effective and convenient manner, including, inter alia, topical, oral, anal, vaginal, intravenous, intraperitoneal, intramuscular, subcutaneous, intranasal or intradermal routes. It is also preferable to use these compositions in combination with a non-sterile or sterile carrier (s) for use in cells, tissues or organisms, for example, a pharmaceutical carrier suitable for administration to a subject. Such compositions comprise, for example, a media supplement or a therapeutically effective amount of a compound of the present invention, a quinolone, preferably a gemifloxacin compound, and a pharmaceutically acceptable carrier or excipient. Such carriers include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol and combinations thereof. The prescription is
It should be adapted to the mode of administration.

The quinolone compounds, especially gemifloxacin compounds and compositions of the method of the present invention can be used alone or as bacterial efflux pump inhibitors or antibiotics, especially non-quinolone compounds such as beta-lactam antibiotics and the like. May be used in combination with other compounds. In treatment or as a prophylactic, the active agent of the method of the invention is preferably
It is administered to an individual as an injectable composition, for example, a sterile aqueous dispersion, preferably an isotonic sterile aqueous dispersion.

Alternatively, for topical application of the gemifloxacin compound or composition in the method of the present invention,
For example, ointments, creams, lotions, eye ointments, eye drops,
Ear drops, mouth washes, impregnated trauma materials and sutures and may be formulated in aerosol form, including, for example, preservatives, solvents to aid drug penetration and emollients in ointments and creams. It may contain suitable conventional additives. Such topical formulations may also contain compatible conventional carriers, such as cream or ointment bases and ethanol or oleyl alcohol for lotions. Such carriers may range from about 1% by weight of the formulation to
Make up about 98% by weight; more usually, about 80% of the formulation.
Make up the weight percentage.

For administration to mammals, especially humans,
Antibacterial effective amount of active drug is 0.001 mg / k / day
g to 10 mg / kg, typically from about 0.1 mg / kg to
It is expected that the dosage level will be 1 mg / kg, preferably about 1 mg / kg. In any event, the consulting physician will determine the actual dosage which will be most suitable for the individual and will vary with the age, weight and response of the particular individual. The above dosages are examples of the average case. Of course, there are individual examples where higher or lower dosage ranges are appropriate and such examples are within the scope of the invention. It is preferred to choose a dose that modulates the metabolism of the bacterium in such a way as to inhibit or stop the growth of the bacterium or by killing the bacterium. One skilled in the art may identify the amount as provided herein or using other methods known in the art, for example, by a MIC test.

A further embodiment of the present invention is to provide a method of contacting, further comprising contacting an indwelling device in a patient. Indwelling devices include, but are not limited to, surgical implants, prosthetic devices and catheters, ie, devices that are introduced into an individual's body and remain in place for an extended period of time. Such devices include, for example, artificial joints, heart valves, pacemakers, vascular grafts, vascular catheters, cerebrospinal fluid shunts, urethral catheters, and continuous ambulatory peritoneal dialysis (CAPD) catheters. Immediately prior to insertion of an indwelling device, a quinolone, particularly a gemifloxacin compound or composition, of the present invention may be administered by injection to achieve a systemic effect on the relevant bacteria, preferably anaerobic pathogens. The treatment may continue after the surgery and while the device is in the body. In addition, the composition may also be used to extend pre- and post-operative management in any surgery to prevent bacterial wound infections caused by or associated with anaerobic pathogens. Good.

In addition to the treatments described above, the gemifloxacin compound or composition used in the method of the present invention is generally used as a wound healing agent to prevent adhesion of bacteria, especially anaerobic pathogens, to matrix proteins. However, it may be exposed in wound tissue and, alternatively, may be used for prophylactic use in dental treatment and may be used in conjunction with antibiotic prophylaxis. Alternatively, the quinolone of the present invention, particularly the gemifloxacin compound or composition, may be used to expose the indwelling device immediately prior to insertion. The active agent is preferably 1 μl for exposure of a wound or an internal device.
Present at a concentration of g / ml to 10 mg / ml.

Also, according to the present invention, a mammal that is suspected of or is at risk of being infected with an anaerobic pathogen is provided with an antimicrobial effective amount of a composition comprising a quinolone, particularly a gemifloxacin compound. There is provided a method for treating or preventing a bacterial infection due to an anaerobic pathogen, comprising the step of administering to an animal, particularly a human. Furthermore, a preferred object of the present invention is that the anaerobic pathogen is Peptostreptococcus anerobius, Peptostreptococcus athacarolicus, Peptostreptococcus indolicus,
Peptostreptococcus magnus, Peptostreptococcus micros, Peptostreptococcus prevotii, Staphylococcus saccharolyticus,
Atopodium parvulus, Streptococcus consteratas, Streptococcus intermedius, Gemera morbirolum, Clostridium clostridiiforme, Clostridium difficile, Clostridium perfringens, Clostridium septicum, Clostridium solderii, morstrodium P. bacteria Acnes, Propionibacterium granulosam, E. bacteria rentum, Actinomyces odoronticus, Bifidobacterium adressentis, Bifidobacterium bifidum, Bifidobacterium breve, Bifid Bacterium longum, Bifidobacterium pseudolongum, Lactobacillus, La Tobacillus brevis subsp. Brevis, Lactobacillus casei subsp. Bacteroides thetaiotaomicron, Bacteroides Uniformis, Bacteroides Egersii, Bacteroides ureoliticus, Campylobacter gracilis, Suterera wadsworthensis, Prevoterra vivia, Prevoterra bukké, Prevoterra corporis, Intervoterra preparinella media , Boterra Oralis, Prevoterra Oris, Porphyromonas assaccharolytica, Porphyromonas gingivalis, Fusobacterium nucleatum, Fusobacterium barium, Fusobacterium necroforum, Biophylla wadsworthia, Deslohomonas pigra, Chapnositefag yocraselabey・ Palbula, Bayonella dispar, Peptostreptococcus anerobius, Peptostreptococcus assaccharolyticus, Peptostreptococcus magnus, Peptstreptococcus micros, Propionibacterium acnes, Actinomyces species, Clostridium difficile , Clostridium perfringens, Bacteroides distasonis, Bacteroides -B. fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, B. fragilis-group microorganisms (Bi Kakke, B. Egersii, B. ovatus), imipenem-resistant B. fragilis group microorganisms (B. distantasonis, B. fragilis), Prevotera -To provide a method selected from the group consisting of Vivia, Prevotella intermedia, other Prevotella species, Porphyromonas species, Fusobacterium nucleatum and Bayonella species. Other anaerobic pathogens are also included in the method. One of skill in the art may identify these microorganisms as provided herein, as well as using other methods known in the art, for example, MIC tests.

Preferred embodiments of the present invention include, inter alia, methods wherein the composition comprises gemifloxacin or a pharmaceutically acceptable derivative thereof. Each reference cited herein is hereby incorporated by reference in its entirety. In addition, patent applications for which the present application claims priority are all incorporated herein by reference.

Reference 1 Cormican MG, Jones RN. Antimicrobial activity a
nd spectrum of LB20304, a novel fluoronaphthyridon
e. Antimicrob Agents Chemother 1997; 41: 204211.2 Hohl AF, Frei R, et al., International multicenter.
investigation of LB20304, a new fluoronaphthyridon
e. Clin Microbiol Infect 1998; 4: 280284.

 ────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Naoki Kato 40, Shimachi, Gifu City, Gifu Prefecture Inside the School of Medicine, Gifu University (72) Inventor Kari 40, Shimachi, Gifu City, Gifu Prefecture Inside the School of Medicine, Gifu University F-term (reference) 4C065 AA04 BB09 CC01 DD02 EE02 HH08 HH09 JJ04 KK01 LL02 LL08 PP10 4C086 AA01 AA02 CB09 MA01 MA04 NA05 NA14 ZB35

Claims (11)

[Claims] 1. A method for regulating the metabolism of an anaerobic pathogen, comprising contacting the anaerobic pathogen with an antimicrobial effective amount of a composition comprising a gemifloxacin compound or an antimicrobial effective derivative thereof. A method consisting of: 2. The method of claim 1, wherein the anaerobic pathogen is selected from the group consisting of Gram-positive and Gram-negative anaerobic bacteria. 3. A method for treating or preventing a bacterial infection caused by an anaerobic pathogen, wherein the composition is suspected of being infected with the anaerobic pathogen by an antibacterial effective amount of the composition comprising the gemifloxacin compound. Or administering to a mammal at risk of infection. 4. The method according to claim 3, wherein the anaerobic pathogen is selected from the group consisting of Gram-positive and Gram-negative anaerobic bacteria. 5. The method according to claim 3, wherein the mammal is a human. 6. The method of claim 1, wherein the regulation of metabolism is to inhibit bacterial growth. 7. The method according to claim 1, wherein the regulation of metabolism is to kill bacteria. 8. The method of claim 1, wherein contacting the bacterium comprises the additional step of introducing the composition into a mammal. 9. The method according to claim 8, wherein the mammal is a human. 10. The bacterium is Peptostreptococcus.
Anerobius, Peptostreptococcus athacarolicus, Peptstreptococcus indolicus, Peptstreptococcus magnus, Peptstreptococcus micros, Peptstreptococcus micros
Prevotii, Staphylococcus saccharolyticus, Atopodium parvulus, Streptococcus
Consteratas, Streptococcus intermedius, Gemera morbirolum, Clostridium clostridiiforme, Clostridium difficile, Clostridium perfringens, Clostridium septicum, Clostridium sordellii, Clostridium ramosam, Propionibacterium acnes, Propionibacterium granulosaum, Eubacterium rentum, Actinomyces odontricis, Bifidobacterium adressentis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Bi Fidobacterium pseudolongum, Lactobacillus, Lactobacillus brevis subspecies Brevis, Lactobacillus L. casei subsp. Casei, Lactobacillus fermentum, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus salivarium subsp. -Uniformis, Bacteroides Egersii, Bacteroides ureoliticus, Campylobacter grasilis, Suterera wadsworthensis, Prevoterra vivia, Prevoterra bucce, Prevoterra corvolis, Prevoterra heparinolytica, Prevoterra intermedia, Prevoterra melanovorenia, Prevoterra melanenoterrania Oris, Porf Lomonas assaccharolytica, Porphyromonas gingivalis, Fusobacterium nucleatum, Fusobacterium barium, Fusobacterium necroforum, Biophila wadsworthia, Deslohomonas pigra, Chapnocytofag okrasea, Bayonela parbula, Bayoneras disparco Anerobius, P. streptococcus assaccharolyticus, P. streptococcus magnus, P. streptococcus micros, Propionibacterium acnes, Actinomyces sp., Clostridium difficile, Clostridium perfringens, Bacteroides distasonis , Bacteroides fragilis, Bacteroides Sitaiotaomi Clon, Bacteroides uniformis, B. fragilis-group microorganisms (Bi-Kakke, B. Egersii, B. ovatus), imipenem-resistant B. fragilis group microorganisms (B. distantasonis, B. fragilis), Prevotella vivia, Prevotella intermedia 2. The method of claim 1, wherein the method is selected from the group consisting of, other Prevotella species, Porphyromonas species, Fusobacterium nucleatum and Bayonella species. 11. The bacterium according to claim 1, wherein the bacterium is Peptostreptococcus.
Anerobius, Peptostreptococcus athacarolicus, Peptstreptococcus indolicus, Peptstreptococcus magnus, Peptstreptococcus micros, Peptstreptococcus micros
Prevotii, Staphylococcus saccharolyticus, Atopodium parvulus, Streptococcus
Consteratas, Streptococcus intermedius, Gemera morbirolum, Clostridium clostridiiforme, Clostridium difficile, Clostridium perfringens, Clostridium septicum, Clostridium sordellii, Clostridium ramosam, Propionibacterium acnes, Propionibacterium granulosaum, Eubacterium rentum, Actinomyces odontricis, Bifidobacterium adressentis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Bi Fidobacterium pseudolongum, Lactobacillus, Lactobacillus brevis subspecies Brevis, Lactobacillus Scan casei subspecies casei, Lactobacillus fermentum Fell, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus Saribariumu subspecies Saribariumu, Peptostreptococcus Anerobiusu, up Petri Streptococcus A Saccharomyces Lori Atlantica vinegar, Peptostreptococcus Magnus,
Peptostreptococcus micros, Propionibacterium acnes, Actinomyces sp., Clostridium difficile, Clostridium perfringens, Bacteroides distasonis, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformalis group Microorganisms (Bi Kakke, Bie Egersii,
(B. oververtus), imipenem-resistant microorganisms of the B. fragilis group (B. distasonis, B. fragilis), prebotera vivia, prebotera intermedia, other prebotera species, porphyromonas species, fusobacterium nucleatum and bayonella species. The method of claim 1, wherein the method is selected from: