US20020086867A1 - Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria - Google Patents

Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria Download PDF

Info

Publication number
US20020086867A1
US20020086867A1 US09/996,040 US99604001A US2002086867A1 US 20020086867 A1 US20020086867 A1 US 20020086867A1 US 99604001 A US99604001 A US 99604001A US 2002086867 A1 US2002086867 A1 US 2002086867A1
Authority
US
United States
Prior art keywords
strain
pneumophila serogroup
pneumophila
serogroup
method
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US09/996,040
Inventor
Jacques Dubois
Claude St-Pierre
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Corp
Original Assignee
SmithKline Beecham Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US14145799P priority Critical
Priority to US14140999P priority
Priority to US09/395,851 priority patent/US6340689B1/en
Application filed by SmithKline Beecham Corp filed Critical SmithKline Beecham Corp
Priority to US09/996,040 priority patent/US20020086867A1/en
Publication of US20020086867A1 publication Critical patent/US20020086867A1/en
Application status is Abandoned legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • Y02A50/46Medical treatment of waterborne diseases characterized by the agent
    • Y02A50/468The waterborne disease being caused by a bacteria
    • Y02A50/478The waterborne disease being caused by a bacteria of the genus Legionella, i.e. Legionellosis or Legionnaires' disease

Abstract

This invention relates, in part, to newly identified methods of using quinolone antibiotics, particularly a gemifloxacin compound against atypical upper respiratory pathogenic bacteria

Description

  • This invention relates, in part, to methods of using quinolone antibiotics, particularly a gemifloxacin compound, against atypical upper respiratory pathogenic bacteria. [0001]
  • BACKGROUND OF THE INVENTION
  • Quinolones have been shown to be effective to varying degrees against a range of certain respiratory tract pathogens. However, as diseases caused by these pathogens are on the rise, there exists a need for antimicrobial compounds that are more potent and that exhibit a longer post-antibiotic effect than the present group of quinolones. [0002]
  • Gemifloxacin mesylate (SB-265805) is a novel fluoroquinolone useful as a potent antibacterial agent. Gemifloxacin compounds are described in detail in patent application PCT/KR98/00051 published as WO 98/42705. Patent application EP 688772 discloses novel quinoline(naphthyridine)carboxylic acid derivatives, including anhydrous (R,S)-7-(3-aminomethyl-4-methoxyiminopyrrolidin-1 -yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8naphthyridine-3carboxylic acid of formula I [0003]
    Figure US20020086867A1-20020704-C00001
  • PCTIKR98/00051 discloses (R,S)-7-(3-aminomethyl-4-syn-methoxyinino-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro- 1,8-naphthyridine-3-acid methanesulfonate and hydrates thereof including the sesquihydrate. [0004]
  • Provided herein is an invention based, in part, on a significant discovery made using a gemifloxacin compound against a range of variety of Legionella isolated from nosocomial or acquired respiratory tract infections and from environmental sources, demonstrating the activity of the gemifloxacin compound used was superior to a number of quinolones as described in more detail herein. Gemifloxacin compounds are valuable compounds for the treatment of diseases caused by or related to atypical respiratory tract pathogens, thereby filling an unmet medical need. [0005]
  • SUMMARY OF THE INVENTION
  • An object of the invention is a method for modulating metabolism of atypical upper respiratory pathogenic bacteria comprising the step of contacting atypical upper respiratory pathogenic bacteria with an antibacterially effective amount of a composition comprising a gemifloxacin compound, or an antibacterially effective derivative thereof. [0006]
  • A further object of the invention is a method wherein said atypical upper respiratory pathogenic bacteria is selected from the group consisting of: a member of the genus Legionella, a member of the genus, Pseudomonas, [0007] Pseudomonas aeruginosa strain, a Legionella pneumophila strain, a Legionella pnetimophila serogroup 1, a Legionella pnetimophila serogroup 2, a Legionella pneumophila serogroup 3, a Legionella pnetmophila serogroup 4, a Legionella pneumophila serogroup 5, a Legionela pneumophila serogroup 6, a Legionella pneumophila serogroup 7, a Legionella pneumophila serogroup 8, a Legionella dumoffii strain, a Legionella longbeacheae strain, a Legionella micdadei strain, a Legionella oakridgensis strain, a Legionella feelei strain, a Legionella anisa strain, a Legionella sainthelensi strain, a Legionella bozemanii strain. a Legionella gormanii strain, a Legionella wadsworthii strain, a Legionella jordanis strain and a Legionella gormanii strain.
  • Also provided by the invention is a method of treating or preventing a bacterial infection by atypical upper respiratory pathogenic bacteria comprising the step of administering an antibacterially effective amount of a composition comprising a gemifloxacin compound to a mammal suspected of having or being at risk of having an infection with atypical upper respiratory pathogenic bacteria. [0008]
  • A preferred method is provided wherein said modulating metabolism is inhibiting growth of said bacteria or killing said bacteria. [0009]
  • A further preferred method is provided wherein said contacting said bacteria comprises the further step of introducing said composition into a mammal, particularly a human. [0010]
  • Further preferred methods are provided by the invention wherein said bacteria is selected from the group consisting of: a member of the genus Legionella, a member of the genus, Pseudomonas, [0011] Pseudomonas aeruginosa strain, a L pneumophila strain, a L. pneumophila serogroup 1, a L. pneumophila serogroup 2, a L. pneumophila serogroup 3, a L. pneumophila serogroup 4, a L. pneumophila serogroup 5, a L. pneumophila serogroup 6, a L. pnetimophila serogroup 7, a L. pneumophila serogroup 8, a L. dumoffli strain, a L. longbeacheae strain, a L. micdadei strain, a L. oakridgensis strain, a L. feelei strain, a L. anisa strain, a L. sainthelensi strain, a L. bozemanii strain, a L. gorinanii strain, a L. wadsworthii strain, a L. jordanis strain and a L. gormanii strain.
  • A further embodiment of the invention is method for modulating metabolism of atypical upper respiratory pathogenic bacteria comprising the step of contacting atypical upper respiratory pathogenic bacteria with an antibacterially effective amount of a composition comprising a compound selected from the group consisting of: gemifloxacin, ofloxacin, levofloxacin, trovafloxacin, azithromycin, moxifloxacin, ciprofloxacin, clarithromycin, rifampicin and erythromycin; or an antibacterially effective derivative of any of these compounds. [0012]
  • A still further embodiment of the invention is a method of treating or preventing a bacterial infection by atypical upper respiratory pathogenic bacteria comprising the step of administering an antibacterially effective amount of a composition comprising a compound selected from the group consisting of: gemifloxacin, ofloxacin, levofloxacin, trovafloxacin, azithromycin, moxifloxacin, ciprofloxacin, clarithromycin, rifampicin and erythromycin; or an antibacterially effective derivative of any of these compounds, to a mammal suspected of having or being at risk of having an infection with atypical upper respiratory pathogenic bacteria. [0013]
  • It is preferred in the methods of the invention that said contacting is performed once daily. [0014]
  • Various changes and modifications within the spirit and scope of the disclosed invention will become readily apparent to those skilled in the art from reading the following descriptions and from reading the other parts of the present disclosure. [0015]
  • DESCRIPTION OF THE INVENTION
  • The present invention provides, among other things, methods for using a composition comprising a gemifloxacin compound against atypical upper respiratory pathogenic bacteria, especially a member of the genus Legionella, a member of the genus, Pseidomonas, [0016] Pseudomonas aerilginosa strain, a L. pneiumophila strain, a L. pnetimophila serogroup 1, a L. pneumophila serogroup 2, a L. pneumophila serogroup 3, a L pneumophila serogroup 4, a L. pneumophila serogroup 5, a L. pneumophila serogroup 6, a L. pneutmophila serogroup 7, a L. pneumophila serogroup 8, a L. dumoffii strain, a L. longbeacheae strain, a L. micdadei strain, a L. oakridgensis strain, a L feelei strain, a L. anisa strain, a L. sainthelensi strain, a L. bozemanii strain, a L. gormanii strain, a L. wadsworthii strain, a L. jordanis strain or a L. gormanii strain.
  • As used herein “gemifloxacin compound(s)” means a compound having antibacterial activity described in patent application PCT/KR98/00051 published as WO 98/42705, or patent application EP 688772. [0017]
  • This invention was based, in part, on analyses evaluating the in vitro activity and postantibiotic effect (herein “PAE”) of gemifloxacin compared with those of trovafloxacin, moxifloxacin, grepafloxacin, levofloxacin, ofloxacin, ciprofloxacin, azithromycin, clarithromycin, erythromycin and rifampicin against isolates of [0018] Legionella pneumophila and other Legionella spp. Test isolates included L. pneumophila serogroup 1-12 (204), L. dimoffii (10), L. micdadei (10) and L. longbeacheae (7). The PAE was determined by exposing the isolates to the test antimicrobials for 1 hour at four times the minimum inhibitory concentration (herein “MIC”). The antimicrobial was removed by three consecutive centrifugations into fresh broth. The PAE was calculated by measuring bacterial growth kinetics in similar antimicrobial-free cultures. Rifampicin and trovafloxacin were the most active agents tested (MIC90≦0.008 mg/L). Gemifloxacin displayed high potency (MIC90 0.016 mg/L) which was comparable to levofloxacin, grepafloxacin and moxifloxacin (MIC90 0.016 mg/L) and more active than ciprofloxacin and ofloxacin (MIC90 0.03 mg/L). Against L. dumoffii and L. longbeachae, gemifloxacin (MIC90 0.06 mg/L) was as active than ciprofloxacin, ofloxacin, grepafloxacin and moxifloxacin. Against erythromycin-resistant L. pnetimophila, gemifloxacin showed the longest PAE at 4.65 hours, compared with 4.18 hours for grepafloxacin, 3.38 hours for moxifloxacin and 2.83 hours for trovafloxacin. The gemifloxacin PAE was significantly superior to that of rifampicin (0.9 h), clarithromycin (1.9 h) and levofloxacin (2.59 h). Against erythromycin-susceptible L. pneeumophila only gemifloxacin, moxifloxacin, levofloxacin, ofloxacin and ciprofloxacin had a PAE over 3 hours. For erythromycin-resistant Legionella spp. other than L. pneumophila, gemifloxacin, moxifloxacin, levofloxacin and ofloxacin had PAEs in excess of 3 hour, which was significantly longer than the PAE of ciprofloxacin grepafloxacin and erythromycin. The half-life for gemifloxacin and the data presented here indicate a significant PAE to support a once-daily administration of this agent for the treatment of Legionella infections, and this dosing is preferred in the methods of the invention.
  • The MIC range of gemifloxacin against [0019] L. pneunmophila serogroups 1-9 was 0.008-0.06 mg/L (Tables 2 and 3). Gemifloxacin was 5-6-fold more active than erythromycin against L. pneumophila strains tested. Gemifloxacin activity against L. Pneumophila strains was higher than ciprofloxacin and ofloxacin but similar to grepafloxacin and moxifloxacin.
  • [0020] L. pneumophila strains of serogroups 1-3 and 7-9 were more susceptible to gemifloxacin than L. pneumophila serogroups 4-6. Against the most frequent L. pnetimophila, such as serogroup 1, gemifloxacin MlC90 (0.016 mg/L) was superior to azithromycin, clarithromycin, erythromycin, ofloxacin and ciprofloxacin.
  • Against [0021] L. ditmoffii and L. longbeacheae, gemifloxacin, grepafloxacin and clarithromycin showed superior activity to azithromycin and erythromycin (Table 4). Against L. micdadei, gemifloxacin, ciprofloxacin, ofloxacin and moxifloxacin MICs were 5-fold more active than erythromycin.
  • Against erythromycin-resistant [0022] L. pneumophila only gemifloxacin, moxifloxacin and grepafloxacin displayed a mean PAE of >3 hours (Table 5). Clarithromycin, erythromycin and rifampicin showed a PAE of <2 hours against these strains. Against erythromycin-resistant Legionella spp. other than pneumophila, gemifloxacin, grepafloxacin, levofloxacin, ofloxacin and rifampicin displayed a mean PAE of >3 hours, and erythromycin and clarithromycin of <2 hours.
  • Against erythromycin-susceptible [0023] L. pneumophila, gemifloxacin, moxifloxacin, ofloxacin and ciprofloxacin displayed a mean PAE of >3hours. Gemifloxacin and ofloxacin were the only quinolones showing a mean PAE of >2 hours against erythromycin-susceptible Legionella spp. other than L. pneumophila.
  • Gemifloxacin is an effective antimicrobial agent against most Legionella spp. and was significantly superior to the commonly used legionellosis therapy, erythromycin. [0024]
  • Against erythromycin-susceptible [0025] L. pneumophila, the mean PAE of gemifloxacin (3.49 hours) was >1 h longer than that of trovafloxacin, levofloxacin and clarithromycin.
  • Against erythromycin-susceptible Legionella spp. other than pneumophila the mean PAE of gemifloxacin (2.27 hours) was >1 h longer than that of trovafloxacin, moxifloxacin and clarithromycin. [0026]
  • Against erythromycin-resistant [0027] L. pneumophila, the mean PAE of gemifloxacin (4.65 hours) was significantly superior to the mean PAE of trovafloxacin, levofloxacin, ciprofloxacin, azithromycin, clarithromycin, erythromycin and rifampicin. A difference in mean PAE was also noted between gemifloxacin and trovafloxacin against Legionella spp. other than L. pneumophila.
  • The results of this study indicate that gemifloxacin should be a promising agent for the treatment of lower respiratory tract infections caused by Legionella spp. [0028]
    TABLE 1
    Legionella Strains Tested
    Microrganism No. of strains tested
    L. pneumophila 204*
    L. micdadei  10
    L. dumoffli  10
    L. longbeacheae  7
    Others  7
  • [0029]
    TABLE 2
    Susceptibility of Legionella pneumophila Serogroups 1-4
    L. pneumophila serogroup 1 L. pneumophila serogroup 2
    (n = 85) (n = 17)
    MIC (mg/L) MIC (mg/L)
    Antimicrobial Range 50% 90% Range 50% 90%
    Gemifloxacin  0.008-0.06 0.016 ≦0.004  0.008-0.016 0.008 0.016
    Trovafloxacin ≦0.004-0.016 ≦0.004 ≦0.004 ≦0.004 ≦0.004 ≦0.004
    Moxifloxacin ≦0.004-0.03 0.016 0.016 ≦0.004-0.016 0.008 0.008
    Grepafloxacin ≦0.004-0.06 0.016 0.016 ≦0.004-0.03 0.008 0.016
    Levofloxacin ≦0.004-0.016 0.016 0.016 ≦0.004-0.016 0.008 0.008
    Ofloxacin  0.008-0.03 0.03 0.03  0.008-0.03 0.016 0.03
    Ciprofloxacin  0.016-0.25 0.03 0.03 ≦0.004-0.03 0.016 0.016
    Azithromycin  0.008-1.0 0.06 0.5  0.008-0.12 0.06 0.12
    Clarithromycin ≦0.004-0.12 0.06 0.06 ≦0.004-0.06 0.03 0.06
    Erthromycin  0.03-1.0 0.25 1.0  0.008-0.5 0.25 0.25
    Rifampicin ≦0.004-0.008 ≦0.004 0.008 ≦0.004 ≦0.004 ≦0.004
    L. pneumophila serogroup 3 L. pneumophila serogroup 4
    (n = 15) (n = 26)
    MIC (mg/L) MIC (mg/L)
    Antimicrobial Range 50% 90% Range 50% 90%
    Gemifloxacin  0.008-0.016 0.016 0.016  0.008-0.03 0.016 0.03
    Trovafloxacin ≦0.004 ≦0.004 ≦0.004 ≦0.004 ≦0.004 ≦0.004
    Moxifloxacin ≦0.004-0.016 0.008 0.016 ≦0.004-0.016 0.016 0.016
    Grepafloxacin ≦0.004-0.016 0.008 0.016  0.008-0.016 0.008 0.016
    Levofloxacin  0.008-0.016 0.008 0.016  0.004-0.016 0.016 0.016
    Ofloxacin  0.016-0.03 0.016 0.03  0.008-0.03 0.03 0.03
    Ciprofloxacin ≦0.004-0.03 0.03 0.03  0.016-0.12 0.03 0.06
    Azithromycin  0.016-0.25 0.12 0.25  0.008-0.25 0.12 0.12
    Clarithromycin  0.016-0.06 0.03 0.06  0.004-0.06 0.03 0.06
    Erthromycin  0.06-0.5 0.25 0.5  0.016-0.5 0.5 0.5
    Rifampicin ≦0.004 ≦0.004 ≦0.004 ≦0.004-0.008 ≦0.004 ≦0.004
  • [0030]
    TABLE 3
    Susceptibility of L. pneumophila Serogroups 5-12
    L. pneumophila serogroup 5 L. pneumophila serogroup 6
    (n = 15) (n = 40)
    MIC (mg/L) MIC (mg/L)
    Antimicrobial Range 50% 90% Range 50% 90%
    Gemifloxacin  0.03-0.06 0.03 0.03  0.008-0.03 0.016 0.03
    Trovafloxacin ≦0.004-0.008 ≦0.004 ≦0.004 ≦0.004 ≦0.004 ≦0.004
    Moxifloxacin ≦0.004-0.03 0.016 0.016 ≦0.004-0.016 0.008 0.016
    Grepafloxacin ≦0.004-0.003 0.016 0.03 ≦0.004-0.016 0.008 0.016
    Levofloxacin ≦0.004-0.016 0.008 0.016  0.008-0.016 0.008 0.016
    Ofloxacin  0.008-0.03 0.016 0.03  0.008-0.03 0.03 0.03
    Ciprofloxacin  0.016-0.06 0.03 0.03 ≦0.004-0.03 0.03 0.03
    Azithromycin  0.008-0.5 0.03 0.25  0.016-0.25 0.06 0.12
    Clarithromycin  0.03-0.06 0.03 0.06 ≦0.004-0.06 0.016 0.06
    Erthromycin  0.06-1.0 0.25 0.5  0.008-0.25 0.12 0.25
    Rifampicinl ≦0.004 ≦0.004 ≦0.004 ≦0.004-0.008 ≦0.004 ≦0.004
    L. pneumophila serogroup 7 L. pneumophila serogroup 8, 9
    (n = 2) and 12 (n = 4)
    MIC (mg/L) MIC (mg/L)
    Antimicrobial Range 50% 90% Range 50% 90%
    Gemifloxacin  0.008-0.016 0.008 0.016  0.016 0.016 0.016
    Trovafloxacin ≦0.004 ≦0.004 ≦0.004 ≦0.004 ≦0.004 ≦0.004
    Moxifloxacin ≦0.004-0.016 ≦0.004 0.016 0.016 0.016 0.016
    Grepafloxacin ≦0.004-0.008 ≦0.004 0.008  0.008 0.008 0.008
    Levofloxacin  0.008-0.016 0.008 0.016  0.008-0.016 0.008 0.016
    Ofloxacin  0.03 0.03 0.03  0.03 0.03 0.03
    Ciprofloxacin  0.03 0.03 0.03  0.03 0.03 0.03
    Azithromycin  0.06 0.06 0.06  0.06 0.06 0.06
    Clarithromycin  0.016-0.06 0.016 0.06  0.06 0.06 0.06
    Erthromycin  0.12-0.5 0.12 0.5  0.25 0.25 0.25
    Rifampicinl ≦0.004 ≦0.004 ≦0.004 ≦0.004 ≦0.004 ≦0.004
  • [0031]
    TABLE 4
    Susceptibility of Legionella Other than pneumophila
    L. dumoffii L. micdadei
    (n = 10) (n = 10)
    MIC (mg/L) MIC (mg/L)
    Antimicrobial Range 50% 90% Range 50% 90%
    Gemifloxacin  0.06 0.06 0.06  0.008-0.03 0.016 0.03
    Trovafloxacin ≦0.004-0.008 0.008 0.008 ≦0.004 ≦0.004 ≦0.004
    Moxifloxacin  0.008-0.03 0.03 0.03  0.008-0.03 0.016 0.03
    Grepafloxacin  0.06 0.06 0.06 ≦0.004-0.016 0.008 0.016
    Levofloxacin  0.016 0.016 0.016  0.008-0.016 0.016 0.016
    Ofloxacin  0.03 0.03 0.03  0.03 0.03 0.03
    Ciprofloxacin  0.016-0.03 0.016 0.03  0.016-0.03 0.016 0.03
    Azithromycin  0.12-0.25 0.12 0.25  0.016-0.25 0.25 0.25
    Clarithromycin  0.03-0.06 0.03 0.06  0.03-0.12 0.06 0.06
    Erthromycin  0.25-0.5 0.25 0.5  0.25-1 0.5 1
    Rifampicin ≦0.004-0.03 0.008 0.016  0.008 0.008 0.008
    L. longbeacheae Other Legionella spp.
    (n = 7) (n = 7)*
    MIC (mg/L) MIC (mg/L)
    Antimicrobial Range 50% 90% Range 50% 90%
    Gemifloxacin  0.016-0.06 0.06 0.06  0.016-0.06 0.03 0.06
    Trovafloxacin ≦0.004 ≦0.004 ≦0.004 ≦0.004 ≦0.004 ≦0.004
    Moxifloxacin  0.008-0.03 0.016 0.03  0.008-0.03 0.008 0.03
    Grepafloxacin ≦0.004-0.06 0.03 0.06 ≦0.004-0.03 0.03 0.03
    Levofloxacin  0.008-0.016 0.016 0.016  0.008-0.06 0.016 0.016
    Ofloxacin  0.016-0.03 0.03 0.03 ≦0.004-0.06 0.016 0.06
    Ciprofloxacin ≦0.004-0.03 0.016 0.03 ≦0.004-0.03 0.016 0.03
    Azithromycin  0.016-0.25 0.12 0.25  0.016-0.5 0.12 0.5
    Clarithromycin  0.008-0.06 0.06 0.06 ≦0.004-0.12 0.03 0.12
    Erthromycin  0.008-0.5 0.25 0.5  0.016-1 0.5 1
    Rifampicin ≦0.004-0.06 ≦0.004 0.06 ≦0.004-0.008 ≦0.004 0.008
  • [0032]
    TABLE 5
    Mean PAE of Antimicrobials Against Erthromycin-resistant and -susceptible Strains
    of Legionella
    Mean PAE (h)*
    Erthromycin-resistant strains Erthromycin-susceptible strains
    Antimicrobial L. pneumophila Legionella spp. L. pneumophila Legionella spp.**
    (4 × MIC) (n = 7) (n = 9) (n = 15) (n = 13)
    Gemifloxacin 4.65 ± 3 3.34 ± 2 3.49 ± 3 2.27 ± 2
    Trovafloxacin 2.83 ± 2 2.25 ± 2 1.71 ± 1 1.22 ± 1
    Moxifloxacin 3.38 ± 2 2.02 ± 1 3.59 ± 3 1.18 ± 2
    Grepafloxacin 4.18 ± 3 3.67 ± 1 2.62 ± 3 1.67 ± 1
    Levofloxacin 2.59 ± 2 3.24 ± 1 2.14 ± 2 1.35 ± 1
    Ofloxacin 2.99 ± 1 4.13 ± 2 3.53 ± 3 3.04 ± 2
    Ciprofloxacin 2.86 ± 2 2.13 ± 3 3.61 ± 2 1.86 ± 2
    Azithromycin 2.16 ± 1 2.13 ± 1 2.91 ± 3 1.86 ± 2
    Clarithromycin 1.90 ± 1 1.60 ± 2 0.72 ± 2 0.98 ± 2
    Erythromycin 0.90 ± 1 0.44 ± 1 0.93 ± 1 2.06 ± 2
    Rifampicin 0.93 ± 4  5.6 ± 3 2.86 ± 5 3.09 ± 4
  • The invention provides a method for modulating metabolism of atypical upper respiratory pathogenic bacteria. Skilled artisans can readily choose atypical upper respiratory pathogenic bacteria or patients infected with or suspected to be infected with these organisms to practice the methods of the invention. Alternatively, the bacteria useful in the methods of the invention may be those described herein. [0033]
  • The contacting step in any of the methods of the invention may be performed in many ways that will be readily apparent to the skilled artisan. However, it is preferred that the contacting step comprises provision of a composition comprising a gemifloxacin compound to a mammal, particularly a human patient in need of such composition or directly to bacteria in culture medium or buffer or on a surface. [0034]
  • For example, when contacting a human patient or contacting said bacteria in a human patient or in vitro, the compositions comprising a gemifloxacin compound, preferably pharmaceutical compositions may be administered in any effective, convenient manner including, for instance, administration by topical, oral, anal, vaginal, intravenous, intraperitoneal, intramuscular, subcutaneous, intranasal or intradermal routes among others. [0035]
  • It is also preferred that these compositions be employed in combination with a non-sterile or sterile carrier or carriers for use with cells, tissues or organisms, such as a pharmaceutical carrier suitable for administration to a subject. Such compositions comprise, for instance, a media additive or a therapeutically effective amount of a compound of the invention, preferably a gemifloxacin compound, and a pharmaceutically acceptable carrier or excipient. Such carriers may include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol and combinations thereof. The formulation should suit the mode of administration. [0036]
  • Gemifloxacin compounds and compostions of the methods of the invention may be employed alone or in conjunction with other compounds, such as bacterial efflux pump inhibtor compounds or antibiotic compounds, particularly non-quinolone compounds, e.g., beta-lactam antibiotic compounds. [0037]
  • In therapy or as a prophylactic, the active agent of a method of the invention is preferably administered to an individual as an injectable composition, for example as a sterile aqueous dispersion, preferably an isotonic one. [0038]
  • Alternatively, the gemifloxacin compounds or compositions in the methods of the invention may be formulated for topical application for example in the form of ointments, creams, lotions, eye ointments, eye drops, ear drops, mouthwash, impregnated dressings and sutures and aerosols, and may contain appropriate conventional additives, including, for example, preservatives, solvents to assist drug penetration, and emollients in ointments and creams. Such topical formulations may also contain compatible conventional carriers, for example cream or ointment bases, and ethanol or oleyl alcohol for lotions. Such carriers may constitute from about 1% to about 98% by weight of the formulation; more usually they will constitute up to about 80% by weight of the formulation. [0039]
  • For administration to mammals, and particularly humans, it is expected that the antibacterially effective amount is a daily dosage level of the active agent from 0.001 mg/kg to 10 mg/kg, typically around 0.1 mg/kg to 1 mg/kg, preferably about 1 mg/kg. A physician, in any event, will determine an actual dosage that is most suitable for an individual and will vary with the age, weight and response of the particular individual. The above dosages are exemplary of the average case. There can, of course, be individual instances where higher or lower dosage ranges are merited, and such are within the scope of this invention. It is preferred that the dosage is selected to modulate metabolism of the bacteria in such a way as to inhibit or stop growth of said bacteria or by killing said bacteria. The skilled artisan may identify this amount as provided herein as well as using other methods known in the art, e.g. by the application MIC tests. [0040]
  • A further embodiment of the invention provides for the contacting step of the methods to further comprise contacting an in-dwelling device in a patient. In-dwelling devices include, but are not limited to, surgical implants, prosthetic devices and catheters, i.e., devices that are introduced to the body of an individual and remain in position for an extended time. Such devices include, for example, artificial joints, heart valves, pacemakers, vascular grafts, vascular catheters, cerebrospinal fluid shunts, urinary catheters, and continuous ambulatory peritoneal dialysis (CAPD) catheters. [0041]
  • A gemifloxacin compound or composition of the invention may be administered by injection to achieve a systemic effect against relevant bacteria, preferably a atypical upper respiratory pathogenic bacteria, shortly before insertion of an in-dwelling device. Treatment may be continued after surgery during the in-body time of the device. In addition, the composition could also be used to broaden perioperative cover for any surgical technique to prevent bacterial wound infections caused by or related to atypical upper respiratory pathogenic bacteria. [0042]
  • In addition to the therapy described above, a gemifloxacin compound or composition used in the methods of this invention may be used generally as a wound treatment agent to prevent adhesion of bacteria to matrix proteins, particularly atypical upper respiratory pathogenic bacteria, exposed in wound tissue and for prophylactic use in dental treatment as an alternative to, or in conjunction with, antibiotic prophylaxis. [0043]
  • Alternatively, a gemifloxacin compound or composition of the invention may be used to bathe an indwelling device immediately before insertion. The active agent will preferably be present at a concentration of [0044] 1μg/'ml to 10mg/ml for bathing of wounds or indwelling devices.
  • Also provided by the invention is a method of treating or preventing a bacterial infection by atypical upper respiratory pathogenic bacteria comprising the step of administering an antibacterially effective amount of a composition comprising a gemifloxacin compound to a mammal, preferably a human, suspected of having or being at risk of having an infection with atypical upper respiratory pathogenic bacteria. [0045]
  • While a preferred object of the invention provides a method wherein said atypical upper respiratory pathogenic bacteria is selected from the group consisting of: a member of the genus Legionella, a member of the genus, Pseudomonas, [0046] Pseudomonas aeruginosa strain, a L. pneumophila strain, a L. pneumophila serogroup 1, a L. pneumophila serogroup 2, a L. pneumophila serogroup 3, a L. pneumophila serogroup 4, a L. pneumophila serogroup 5, a L. Pneumophila serogroup 6, a L. pneumophila serogroup 7, a L. pneumophila serogroup 8, a L. dumoffii strain, a L. longbeacheae strain, a L. micdadei strain, a L. oakridgensis strain, a L. feelei strain, a L. anisa strain, a L. sainthelensi strain, a L. bozemanii strain, a L. gormanii strain, a L. wadsworthii strain, a L. jordanis; strain and a L. gormanii strain. Other atypical upper respiratory pathogenic bacteria may also be included in the methods. The skilled artisan may identify these organisms as provided herein as well as using other methods known in the art, e.g. MIC tests.
  • Preferred embodiments of the invention include, among other things, methods wherein said composition comprises gemifloxacin, or a pharmaceutically acceptable derivative thereof. [0047]
  • EXAMPLES
  • The present invention is further described by the following examples. The examples are provided solely to illustrate the invention by reference to specific embodiments. This exemplification's, while illustrating certain specific aspects of the invention, do not portray the limitations or circumscribe the scope of the disclosed invention. [0048]
  • All examples were carried out using standard techniques, which are well known and routine to those of skill in the art, except where otherwise described in detail. [0049]
  • All parts or amounts set out in the following examples are by weight, unless otherwise specified. [0050]
  • Example 1 Bacterial Strains
  • A variety of Legionella were isolated from respiratory tract and environmental sources. Identification of organisms was by standard methods know in the art (for example, see, Washington, C. W. Jr. Legionella. In: Murray et al., eds. [0051] Manual of Clinical Microbiology. 6th ed. American Society of Microbiology 1995:533-544).
  • Example 2 Susceptibility Testing
  • MICs were determined by standard 2-fold agar dilution procedure using Buffered Yeast Extract agar (herein “BYE”) (National Committee for Clinical Laboratory Standards: Methods for antimicrobial susceptibility tests for bacteria that growth aerobically, approved standards M 7-A4. National Committee for Laboratory Standards, Villanova, Pa., 1997). [0052]
  • A final innoculum of about 10[0053] 4 colony forming units (herein “CFU”) was inoculated onto the BYE containing doubling dilutions of antibiotics (0.004-256 mg/L). Plates were incubated at 35° C. for 48 hours. An MIC was defined as the lowest concentration of antimicrobial that completely inhibited visible growth. Strains of Pseudomonas aeruginosa ATCC 27853 and L. Pneumophila ATCC 33152 were included as controls.
  • Example 3 Determination of PAE
  • The in vitro method using the broth technique (Craig, W. A. [0054] Antibiotics in laboratory medicine. Williams & Wilkins 1986:515-536) was used to determine the PAE with Buffered Yeast extract (BYE). Each strain was exposed to antimicrobial concentration of four times the MIC. Fresh inoculum (1 ml, final concentration of 106-107 CFU/ml) was added to 9 ml of prepared antimicrobial containing medium and to 9 ml of drug-free control medium and incubated at 37° C. for 1-2 hours. Antimicrobial agent was removed by three consecutive centrifugations at 1200×g for 10 minutes. Counts of CFU/ml were performed on all cultures at time zero, before and after washing, and every 1 hour until turbidity develops. The counts of CFU/ml were graphed and the duration of PAE was calculated by equation:
  • PAE=T−C
  • where T is the time required for the count of CFU in the test culture to increase 1 log[0055] 10 above the count observed immediately after drug removal, and C is the time required for the count of untreated control culture to increase by 1 log10 above the count observed immediately after the completion of the same procedure used on the test culture for drug removal.
  • Each reference cited herein is hereby incorporated by reference in its entirety. Moreover, each patent application to which this application claims priority is hereby incorporated by reference in its entirety. [0056]

Claims (16)

What is claimed is:
1. A method for modulating metabolism of atypical upper respiratory pathogenic bacteria comprising the step of contacting atypical upper respiratory pathogenic bacteria with an antibacterially effective amount of a composition comprising a gemifloxacin compound, or antibacterially effective derivatives thereof.
2. The method of claim 1 wherein said atypical upper respiratory pathogenic bacteria is selected from the group consisting of:
a member of the genus Legionella, a member of the genus, Pseudomonas, Pseudomonas aeruginosa strain, a L. pneumophila strain, a L. Pneumophila serogroup 1, a L. Pneumophila serogroup 2, a L. pneumophila serogroup 3, a L. pneumophila serogroup 4, a L. Pneumophila serogroup 5, a L. pneumophila serogroup 6, a L. pneumophila serogroup 7, a L. pneumophila serogroup 8, a L. dumoffii strain, a L. longbeacheae strain, a L. micdadei strain, a L. oakridgensis strain, a L. feelei strain, a L. anisa strain, a L. sainthelensi strain, a L. bozemanii strain, a L. gormanii strain, a L. wadsworthii strain, a L. jordanis; strain and a L. gormanii strain.
3. A method of treating or preventing a bacterial infection by atypical upper respiratory pathogenic bacteria comprising the step of administering an antibacterially effective amount of a composition comprising a gemifloxacin compound to a mammal suspected of having or being at risk of having an infection with atypical upper respiratory pathogenic bacteria.
4. The method of claim 3 wherein said atypical upper respiratory pathogenic bacteria is selected from the group consisting of: a member of the genus Legionella, a member of the genus, Pseudomonas, Pseudomonas aeruginosa strain, a L. pneumophila strain, a L. pneumophila serogroup 1, a L. pneumophila serogroup 2, a L. pneumophila serogroup 3, a L. pneumophila serogroup 4, a L. pneumophila serogroup 5, a L. pneumophila serogroup 6, a L. pneumophila serogroup 7, a L. pneumophila serogroup 8, a L. dumoffii strain, a L. longbeacheae strain, a L. micdadei strain, a L. oakridgensis strain, a L. feelei strain, a L. anisa strain, a L. sainthelensi strain, a L. bozemanii strain, a L. gormanii strain, a L. wadsworthii strain, a L. jordanis; strain and a L. gormanii strain.
5. The method of claim 1 wherein said modulating metabolism is inhibiting growth of said bacteria.
6. The method of claim 1 wherein said modulating metabolism is killing said bacteria.
7. The method of claim 1 wherein said contacting said bacteria comprises the further step of introducing said composition into a mammal.
8. The method of claim 3 wherein said mammal is a human.
9. The method of claim 7 wherein said mammal is a human.
10. The method of claim 1 wherein said bacteria is selected from the group consisting of: a member of the genus Legionella, a member of the genus, Pseudomonas, Pseudomonas aeruginosa strain, a L. pneumophila strain, a L. pneumophila serogroup 1, a L. pneumophila serogroup 2, a L. pneumophila serogroup 3, a L. pneumophila serogroup 4, a L. pneumophila serogroup 5, a L. pneumophila serogroup 6, a L. Pneumophila serogroup 7, a L. pneumophila serogroup 8, a L. dumoffii strain, a L. longbeacheae strain, a L. micdadei strain, a L. oakridgensis strain, a L. feelei strain, a L. anisa strain, a L. sainthelensi strain, a L. bozemanii strain, a L. gormanii strain, a L. wadsworthii strain, a L. jordanis; strain and a L. gormanii strain.
11. The method of claim 1 wherein said bacteria is selected from the group consisting of: a member of the genus Legionella, a member of the genus, Pseudomonas, Pseudomonas aeruginosa strain, a L. pneumophila strain, a L. pneumophila serogroup 1, a L. pneumophila serogroup 2, a L. pneumophila serogroup 3, a L. pneumophila serogroup 4, a L. pneumophila serogroup 5, a L. pneumophila serogroup 6, a L. pneumophila serogroup 7, a L. pneumophila serogroup 8, a L dumoffii strain, a L. longbeacheae strain, a L. micdadei strain, a L. oakridgensis strain, a L. feelei strain, a L. anisa strain, a L. sainthelensi strain, a L. bozemanii strain, a L. gormanii strain, a L. wadsworthii strain, a L. jordanis; strain and a L. gormanii strain.
12. A method for modulating metabolism of atypical upper respiratory pathogenic bacteria comprising the step of contacting atypical upper respiratory pathogenic bacteria with an antibacterially effective amount of a composition comprising a compound selected from the group consisting of: gemifloxacin, ofloxacin, levofloxacin, trovafloxacin, azithromycin, moxifloxacin, ciprofloxacin, clarithromycin, rifampicin and erythromycin;
or an antibacterially effective derivative of any of these compounds.
13. The method of claim 12 wherein said bacteria is selected from the group consisting of: a member of the genus Legionella, a member of the genus, Pseudomonas, Pseudomonas aeruginosa strain, a L. pneumophila strain, a L. pneumophila serogroup 1, a L. pneumophila serogroup 2, a L. pneumophila serogroup 3, a L. pneumophila serogroup 4, a L. pneumophila serogroup 5, a L. pneumophila serogroup 6, a L. pneumophila serogroup 7, a L. pneumophila serogroup 8, a L. dumoffii strain, a L. longbeacheae strain, a L. micdadei strain, a L. oakridgensis strain, a L. feelei strain, a L. anisa strain, a L. sainthelensi strain, a L. bozemanii strain, a L. gormanii strain, a L wadsworthii strain, a L. jordanis; strain and a L. gormanii strain.
14. The method of claim 1 wherein said contacting is performed once daily.
15. A method of treating or preventing a bacterial infection by atypical upper respiratory pathogenic bacteria comprising the step of administering an antibacterially effective amount of a composition comprising a compound selected from the group consisting of: gemifloxacin, ofloxacin, levofloxacin, trovafloxacin, azithromycin, moxifloxacin, ciprofloxacin, clarithromycin, rifampicin and erythromycin;
or an antibacterially effective derivative of any of these compounds, to a mammal suspected of having or being at risk of having an infection with atypical upper respiratory pathogenic bacteria.
16. The method of claim 15 wherein said bacteria is selected from the group consisting of: a member of the genus Legionella, a member of the genus, Pseudomonas, Pseudomonas aeruginosa strain, a L. pneumophila strain, a L. pneumophila serogroup 1, a L. pneumophila serogroup 2, a L. pneumophila serogroup 3, a L. pneumophila serogroup 4, a L. pneumophila serogroup 5, a L. pneumophila serogroup 6, a L. pneumophila serogroup 7, a L. pneumophila serogroup 8, a L. dumoffii strain, a L. longbeacheae strain, a L. micdadei strain, a L. oakridgensis strain, a L. feelei strain, a L. anisa strain, a L sainthelensi strain, a L. bozemanii strain, a L. gormanii strain, a L. wadsworthii strain, a L. jordanis; strain and a L. gormanii strain.
US09/996,040 1999-06-29 2001-11-28 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria Abandoned US20020086867A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US14145799P true 1999-06-29 1999-06-29
US14140999P true 1999-06-29 1999-06-29
US09/395,851 US6340689B1 (en) 1999-06-29 1999-09-14 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria
US09/996,040 US20020086867A1 (en) 1999-06-29 2001-11-28 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/996,040 US20020086867A1 (en) 1999-06-29 2001-11-28 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria
US10/290,597 US20030119865A1 (en) 1999-06-29 2002-11-08 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/395,851 Continuation US6340689B1 (en) 1999-06-29 1999-09-14 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US10/290,597 Continuation US20030119865A1 (en) 1999-06-29 2002-11-08 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria

Publications (1)

Publication Number Publication Date
US20020086867A1 true US20020086867A1 (en) 2002-07-04

Family

ID=31720085

Family Applications (3)

Application Number Title Priority Date Filing Date
US09/395,851 Active US6340689B1 (en) 1999-06-29 1999-09-14 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria
US09/996,040 Abandoned US20020086867A1 (en) 1999-06-29 2001-11-28 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria
US10/290,597 Abandoned US20030119865A1 (en) 1999-06-29 2002-11-08 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US09/395,851 Active US6340689B1 (en) 1999-06-29 1999-09-14 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria

Family Applications After (1)

Application Number Title Priority Date Filing Date
US10/290,597 Abandoned US20030119865A1 (en) 1999-06-29 2002-11-08 Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria

Country Status (2)

Country Link
US (3) US6340689B1 (en)
CA (1) CA2282066C (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050209172A1 (en) * 2004-03-17 2005-09-22 American Pharmaceutical Partners, Inc. Lyophilized azithromycin formulation
US20050220871A1 (en) * 2000-03-28 2005-10-06 Schwarz Franz X Taste masking granules
US20060116336A1 (en) * 2004-03-17 2006-06-01 American Pharmaceutical Partners, Inc. Lyophilized azithromycin formulation
US20060276483A1 (en) * 2005-05-18 2006-12-07 Surber Mark W Aerosolized fluoroquinolones and uses thereof
US8357696B2 (en) 2005-05-18 2013-01-22 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US8629139B2 (en) 2008-10-07 2014-01-14 Mpex Pharmaceuticals, Inc. Topical use of Levofloxacin for reducing lung inflammation
US8815838B2 (en) 2008-10-07 2014-08-26 David C. Griffith Aerosol fluoroquinolone formulations for improved pharmacokinetics
US9700564B2 (en) 2009-09-04 2017-07-11 Horizon Orphan Llc Use of aerosolized levofloxacin for treating cystic fibrosis

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2281817C (en) * 1999-06-29 2008-07-29 Smithkline Beecham Corporation Methods of use of fluoroquinolone compounds against maxillary sinus pathogenic bacteria
US20050032813A1 (en) * 1999-09-14 2005-02-10 Jacques Dubois Methods of use of fluoroquinolone compounds against maxillary sinus pathogenic bacteria
HU230030B1 (en) 1999-10-08 2015-05-28 Debiopharm Int Sa Fab i inhibitors
SK13722002A3 (en) * 2000-02-29 2003-08-05 Teva Pharmaceutical Industries Ltd. Processes for preparing clarithromycin and clarithromycin intermediate, essentially oxime-free clarithromycin, and pharmaceutical composition comprising the same
US20040023983A1 (en) * 2001-11-08 2004-02-05 Chalker Alison F. Methods of use of fluoroquinolone compounds against pathogenic helicobacter bacteria
WO2002038156A2 (en) * 2000-11-10 2002-05-16 Smithkline Beecham Corporation Methods of use of fluoroquinolone compounds against pathogenic helicobacter bacteria
CA2444597A1 (en) * 2001-04-06 2002-10-06 Affinium Pharmaceuticals, Inc. Fab i inhibitors
DK1575951T3 (en) 2002-12-06 2014-09-15 Debiopharm Int Sa Heterocyclic compounds, to processes for their preparation and their use in therapy
WO2004082586A2 (en) 2003-03-17 2004-09-30 Affinium Pharmaceuticals, Inc. Phamaceutical compositions comprising inhibitors of fab i and further antibiotics
CA2568914C (en) * 2004-06-04 2013-09-24 Affinium Pharmaceuticals, Inc. Therapeutic agents, and methods of making and using the same
HU0500879A2 (en) * 2005-09-22 2007-05-29 Sanofi Aventis Amide derivatives as ccr3 receptor ligands, process for producing them, pharmaceutical compositions containing them and their use and intermediates
HU0500877A2 (en) * 2005-09-22 2007-05-29 Sanofi Aventis Amide derivatives as ccr3 receptor ligands, process for producing them, pharmaceutical compositions containing them and their use and intermediates
HU0500886A2 (en) * 2005-09-23 2007-05-29 Sanofi Aventis Amide derivatives as ccr3 receptor ligands, process for producing them, pharmaceutical compositions containing them and their use
EP1973902A2 (en) * 2005-12-05 2008-10-01 Affinium Pharmaceuticals, Inc. 3-heterocyclylacrylamide compounds as fabi inhibitors and antibacterial agents
JP5468899B2 (en) 2006-07-20 2014-04-09 アフィニウム ファーマシューティカルズ, インク.Affinium Pharmaceuticals, Inc. Acrylamide derivatives as inhibitors Fabi
WO2008098374A1 (en) 2007-02-16 2008-08-21 Affinium Pharmaceuticals, Inc. Salts, prodrugs and polymorphs of fab i inhibitors
CN104684922B (en) 2012-06-19 2016-10-26 德彪药业国际股份公司 (E) -N- methyl -n - ((3- methyl-benzofuran-2-yl) methyl) -3- (7-oxo-5,6,7,8-tetrahydro-1, prodrug derivatives 8- naphthyridin-3-yl) acrylamide

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK0688772T3 (en) 1994-06-16 1999-11-01 Lg Chemical Ltd Quinolinecarboxylic acids with 7- (4-aminomethyl-3-oxime) -pyrrolidinsubstituenter and process for their preparation
MA24500A1 (en) 1997-03-21 1998-10-01 Lg Life Sciences Ltd Derivative of the carboxylic acid salt naphthyridine.

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050220871A1 (en) * 2000-03-28 2005-10-06 Schwarz Franz X Taste masking granules
US20080095855A1 (en) * 2000-03-28 2008-04-24 Schwarz Franz X Taste Masking Granules
US20060116336A1 (en) * 2004-03-17 2006-06-01 American Pharmaceutical Partners, Inc. Lyophilized azithromycin formulation
US20050209172A1 (en) * 2004-03-17 2005-09-22 American Pharmaceutical Partners, Inc. Lyophilized azithromycin formulation
US7468428B2 (en) 2004-03-17 2008-12-23 App Pharmaceuticals, Llc Lyophilized azithromycin formulation
US8546423B2 (en) 2005-05-18 2013-10-01 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US7838532B2 (en) 2005-05-18 2010-11-23 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US8357696B2 (en) 2005-05-18 2013-01-22 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US8524735B2 (en) 2005-05-18 2013-09-03 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US20060276483A1 (en) * 2005-05-18 2006-12-07 Surber Mark W Aerosolized fluoroquinolones and uses thereof
US8524734B2 (en) 2005-05-18 2013-09-03 Mpex Pharmaceuticals, Inc. Aerosolized fluoroquinolones and uses thereof
US8629139B2 (en) 2008-10-07 2014-01-14 Mpex Pharmaceuticals, Inc. Topical use of Levofloxacin for reducing lung inflammation
US8815838B2 (en) 2008-10-07 2014-08-26 David C. Griffith Aerosol fluoroquinolone formulations for improved pharmacokinetics
US9326936B2 (en) 2008-10-07 2016-05-03 Raptor Pharmaceuticals, Inc. Aerosol fluoroquinolone formulations for improved pharmacokinetics
US9717738B2 (en) 2008-10-07 2017-08-01 Horizon Orphan Llc Aerosol fluoroquinolone formulations for improved pharmacokinetics
US10149854B2 (en) 2008-10-07 2018-12-11 Horizon Orphan Llc Aerosol fluoroquinolone formulations for improved pharmacokinetics
US9700564B2 (en) 2009-09-04 2017-07-11 Horizon Orphan Llc Use of aerosolized levofloxacin for treating cystic fibrosis
US10231975B2 (en) 2009-09-04 2019-03-19 Horizon Orphan Llc Use of aerosolized levofloxacin for treating cystic fibrosis

Also Published As

Publication number Publication date
US20030119865A1 (en) 2003-06-26
CA2282066C (en) 2010-09-07
US6340689B1 (en) 2002-01-22
CA2282066A1 (en) 2000-12-29

Similar Documents

Publication Publication Date Title
Gentry et al. Oral ciprofloxacin compared with parenteral antibiotics in the treatment of osteomyelitis.
Graninger et al. Nosocomial bacteremia due to Enterococcus faecalis without endocarditis
North et al. Levofloxacin, a second‐generation fluoroquinolone
Ernst et al. Levofloxacin and trovafloxacin: the next generation of fluoroquinolones?
Donnenfeld et al. Penetration of topically applied ciprofloxacin, norfloxacin, and ofloxacin into the aqueous humor
Kim et al. Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients
US9370508B2 (en) Imidazoquinolines as dual lipid kinase and mTOR inhibitors
US5883074A (en) Potentiators of antibacterial agents
JP5414138B2 (en) The use of chemotherapeutic agents
Wong et al. Penetration of antimicrobial agents into bronchial secretions
Hoogkamp-Korstanje In-vitro activities of ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin, pefloxacin, sparfloxacin and trovafloxacin against gram-positive and gram-negative pathogens from respiratory tract infections.
Swerdloff et al. Severe candidal infections in neutropenic patients
WO1996016650A1 (en) Antibacterial or bactericide comprising 2-aminothiazole derivative and salts thereof
Parks et al. Comparison of topical ciprofloxacin to conventional antibiotic therapy in the treatment of ulcerative keratitis
US7033604B2 (en) Composition for topical administration
Eykyn et al. Prophylactic peroperative intravenous metronidazole in elective colorectal surgery
Wang et al. Treatment of typhoid fever with ofloxacin
Drancourt et al. Oral treatment of Staphylococcus spp. infected orthopaedic implants with fusidic acid or ofloxacin in combination with rifampicin.
EP1172105A1 (en) Antifungal compositions
CA2523651A1 (en) Antibacterial methods and compositions
Pickerill et al. Comparison of the fluoroquinolones based on pharmacokinetic and pharmacodynamic parameters
Hackbarth et al. Serum bactericidal activity of rifampin in combination with other antimicrobial agents against Staphylococcus aureus.
Diamond et al. Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial keratitis: a new method for comparative evaluation of ocular drug penetration.
Azoulay-Dupuis et al. Antipneumococcal activity of ciprofloxacin, ofloxacin, and temafloxacin in an experimental mouse pneumonia model at various stages of the disease
Goldschmidt et al. Prevention of catheter-related infections by silver coated central venous catheters in oncological patients