title: In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinolone.
abstract: The in vitro and in vivo activities of T-3811ME, a novel des-F(6)-quinolone, were evaluated in comparison with those of some fluoroquinolones, including a newly developed one, trovafloxacin. T-3811, a free base of T-3811ME, showed a wide range of antimicrobial spectra, including activities against Chlamydia trachomatis, Mycoplasma pneumoniae, and Mycobacterium tuberculosis. In particular, T-3811 exhibited potent activity against various gram-positive cocci, with MICs at which 90% of the isolates are inhibited (MIC90s) of 0.025 to 6.25 microgram/ml. T-3811 was the most active agent against methicillin-resistant Staphylococcus aureus and streptococci, including penicillin-resistant Streptococcus pneumoniae (PRSP). T-3811 also showed potent activity against quinolone-resistant gram-positive cocci with GyrA and ParC (GrlA) mutations. The activity of T-3811 against members of the family Enterobacteriaceae and nonfermentative gram-negative rods was comparable to that of trovafloxacin. In common with other fluoroquinolones, T-3811 was highly active against Haemophilus influenzae, Moraxella catarrhalis, and Legionella sp., with MIC90s of 0.0125 to 0.1 microgram/ml. T-3811 showed a potent activity against anaerobic bacteria, such as Bacteroides fragilis and Clostridium difficile. T-3811 was the most active agent against C. trachomatis (MIC, 0.008 microgram/ml) and M. pneumoniae (MIC90, 0.0313 microgram/ml). The activity of T-3811 against M. tuberculosis (MIC90, 0.0625 microgram/ml) was potent and superior to that of trovafloxacin. In experimental systemic infection with a GrlA mutant of S. aureus and experimental pneumonia with PRSP in mice, T-3811ME showed excellent therapeutic efficacy in oral and subcutaneous administrations.
authors.affiliation: Research Laboratories, Toyama Chemical Co., Ltd., Toyama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takahata
authors.forename: J
authors.initials: J
authors.lastname: Mitsuyama
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashiro
authors.forename: M
authors.initials: M
authors.lastname: Yonezawa
authors.forename: H
authors.initials: H
authors.lastname: Araki
authors.forename: Y
authors.initials: Y
authors.lastname: Todo
authors.forename: S
authors.initials: S
authors.lastname: Minami
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Narita
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D002939:Ciprofloxacin / Q000494:pharmacology; D024841:Fluoroquinolones; D007211:Indoles / Q000008:administration & dosage* / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D054833:Isoindoles; D008297:Male; D051379:Mice; D009287:Naphthyridines / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D015363:Quinolones / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D007211:Indoles; D054833:Isoindoles; D009287:Naphthyridines; D015363:Quinolones; C118960:T 3811ME; D002939:Ciprofloxacin; C080163:trovafloxacin; D015242:Ofloxacin