title: [In vitro and in vivo antibacterial activities of pazufloxacin mesilate, a new injectable quinolone].
abstract: We investigated the in vitro and in vivo antibacterial activities of pazufloxacin mesilate (PZFX mesilate), a new injectable quinolone, and obtained the following results. 1) The MIC50 and MIC90 values of PZFX against clinically isolated Gram-positive and -negative bacteria, ranged from 0.0125 to 12.5 micrograms/ml and 0.025 to 100 micrograms/ml, respectively. PZFX showed broad spectrum activity. The antibacterial activities of PZFX against quinolone-susceptible, methicillin-resistant Staphylococcus aureus, beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae, extended spectrum beta-lactamase possessing Klebsiella pneumoniae and imipenem/cilastatine (IPM/CS)-resistant Pseudomonas aeruginosa were superior to those of ceftazidime (CAZ), ceftriaxone, IPM/CS, meropenem and panipenem/betamipron. 2) PZFX showed superior bactericidal activity against S. aureus, Escherichia coli, Proteus mirabilis, Serratia marcescens and P. aeruginosa to those of CAZ and IPM/CS after treatment for 15 minutes at the drug concentration equivalent to that in human serum at clinical dose to be continued for 15 minutes. 3) CAZ and IPM/CS had no bactericidal activity at the 16 times of MIC against P. aeruginosa in human polymorphonuclear leucocytes, while PZFX exhibited potent bactericidal activity in a dose-dependent manner against such bacteria. 4) PZFX inhibited both DNA gyrase and topoisomerase IV from S. aureus at nearly the same level. PZFX showed poor inhibitory activity against topoisomerase II from human placenta and showed high selectivity to bacterial topoisomerase. 5) PZFX mesilate showed superior therapeutic activity to that of CAZ with following infection model caused by S. aureus and P. aeruginosa or each; systemic infection with cyclophosphamide-treated mice, systemic infection in mice with high challenge doses, CMC pouch infection in rat, and calculus infection in rat bladder. 6) Intravenous administration of PZFX with high plasma concentration just after administration, showed more excellent therapeutic effect against the rat intraperitoneal infection, than p.o. and s.c. administration.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Nomura
authors.forename: Junichi
authors.initials: J
authors.lastname: Mitsuyama
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Furuta
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamada
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Nakata
authors.forename: Toshiko
authors.initials: T
authors.lastname: Fukuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takahata
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Minami
mesh_terms: D042462:4-Quinolones; D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D015377:Cilastatin / Q000494:pharmacology; D000077728:Cilastatin, Imipenem Drug Combination; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D000077731:Meropenem; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D010078:Oxazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013845:Thienamycins / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D042462:4-Quinolones; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004338:Drug Combinations; D024841:Fluoroquinolones; D010078:Oxazines; D013845:Thienamycins; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D015091:beta-Alanine; C075316:panipenem-betamipron; D015377:Cilastatin; C078052:pazufloxacin; D015378:Imipenem; D002443:Ceftriaxone; D000667:Ampicillin; D000077728:Cilastatin, Imipenem Drug Combination; D002442:Ceftazidime; D027101:DNA Topoisomerase IV; D000077731:Meropenem