富马酸西他沙星注射液体内抗菌作用研究
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摘要
目的研究富马酸西他沙星注射液对小鼠细菌感染的体内保护作用。方法选取临床分离的大肠埃希菌、金黄色葡萄球菌、肺炎克雷伯菌和铜绿假单胞菌各1株,以0.5mL的最小致死量(MLD)腹腔注射细菌感染小鼠,建立小鼠腹腔感染模型;于造模1h后,分别静脉注射给予高中低剂量的富马酸西他沙星注射液、盐酸莫西沙星注射液和灌胃给予西他沙星。记录给药后1～7d小鼠存活数;用BLISS法计算ED50、ED95及P值。结果富马酸西他沙星注射液对4株临床分离致病菌的ED50值在0.5～4.0mg/kg,ED95值在1.5～16.3mg/kg,明显优于对照药盐酸莫西沙星注射液和西他沙星(口服)(P<0.01)。结论富马酸西他沙星注射液对临床分离的致病菌表现出较好的体内抗菌作用,其作用明显优于对照药盐酸莫西沙星注射液和西他沙星(口服)。尤其是对铜绿假单胞菌感染小鼠的体内保护作用,富马酸西他沙星注射液优于西他沙星(口服)。因此,富马酸西他沙星注射液有着良好的市场预期,具有很大的开发价值。
Objective To study the protective effects of sitafloxacin fumarate injection on bacterial infections in mice. Methods The clinical isolates of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were selected to establish the mice intraperitoneal infection model by intraperitoneal injection of 0.5 mL minimum lethal dose(MLD) of these bacteria in mice. One hour after the establishment of the model, different concentrations of sitafloxacin fumarate injection and moxifloxacin hydrochloride injection were intravenously administrated and sitafloxacin were orally administrated to the mice, respectively. The survival of the infected mice was monitored for seven days, and the ED50, ED95, and P values were calculated using the BLISS method. Results The ED50 and ED95 of sitafloxacin fumarate injection against four strains of bacteria from clinical isolates were 0.5～4.0 mg/kg and 1.5～16.3 mg/kg, respectively, which were better than those of the control drugs moxifloxacin hydrochloride injection and sitafloxacin(oral)(P<0.01). Conclusion Sitafloxacin fumarate injection showed better antibacterial activity in vivo than moxifloxacin hydrochloride injection and sitafloxacin(oral) against the bacteria from clinical isolates. Especially for the protective effects of Pseudomonas aeruginosa infections in mice, sitafloxacin fumarate injection was superior to that of sitafloxacin(oral). Therefore, sitafloxacin fumarate injection has great development value which is worthy of further research.
Objective To study the protective effects of sitafloxacin fumarate injection on bacterial infections in mice. Methods The clinical isolates of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were selected to establish the mice intraperitoneal infection model by intraperitoneal injection of 0.5 mL minimum lethal dose(MLD) of these bacteria in mice. One hour after the establishment of the model, different concentrations of sitafloxacin fumarate injection and moxifloxacin hydrochloride injection were intravenously administrated and sitafloxacin were orally administrated to the mice, respectively. The survival of the infected mice was monitored for seven days, and the ED50, ED95, and P values were calculated using the BLISS method. Results The ED50 and ED95 of sitafloxacin fumarate injection against four strains of bacteria from clinical isolates were 0.5～4.0 mg/kg and 1.5～16.3 mg/kg, respectively, which were better than those of the control drugs moxifloxacin hydrochloride injection and sitafloxacin(oral)(P<0.01). Conclusion Sitafloxacin fumarate injection showed better antibacterial activity in vivo than moxifloxacin hydrochloride injection and sitafloxacin(oral) against the bacteria from clinical isolates. Especially for the protective effects of Pseudomonas aeruginosa infections in mice, sitafloxacin fumarate injection was superior to that of sitafloxacin(oral). Therefore, sitafloxacin fumarate injection has great development value which is worthy of further research.
引文
[1]官毅红,黄红萍.氟喹诺酮类药物研究概况[J].海峡药学,2014,26(6):100-101.
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[3]田秋月.喹诺酮类药物的研究进展[J].当代化工,2014,43(7):1283-1289.
[4]雷妮,高嵩,陈卫东,等.西他沙星的药理和临床评价[J].中国临床研究,2010,23(10):930-932.
[5]李雪,游雪甫,杨信怡.西他沙星药理研究与临床应用新进展[J].中国抗生素杂志,2013,38(12):893-900.
[6]赵苗.西他沙星片的人体药代动力学及药代动力学/药效学研究[D].上海:复旦大学,2014.
[7]徐叔云,卞如濂,陈修.药理实验方法学(第三版)[M].北京:人民卫生出版社,2002:1664-1666.
[8]孙瑞元.定量药理学[M].北京:人民卫生出版社,1987:154-229.
[9]王琪,康子胜,李家泰.国产盐酸加替沙星对感染小鼠败血症的体内抗菌作用[J].中国抗生素杂志,2001,26(3):208-214.
[10]Sano C,Tatano Y,Shimizu T,et al.Comparative in vitro and in vivo antimicrobial activities of sitafloxacin,gatifloxacin and moxifloxacin against Mycobacterium avium[J].In J Antimicrob Ag,2011,37(4):296-301.
[11]Tanaka M,Onodera Y,Uchida Y,et al.Inhibitory activities of quinolones against DNA gyrase and topoisomerase IVpurified from Staphylococcus aureus[J].Antimicrob Agents Chemother,1997,41(11):2362-2366.
[12]Ping Wu,Laura E L,Kenneth L D,et al.Mechanismofaction of the Des-F(6)quinolone BMS-284756 measured by supercoiling inhibition and cleavablecom-plex assays[J].Antimicorb Agents Chemother,2001,45(14):3660.
[13]Onodera Y,Uchida Y,Tanaka M,et al.Dual inhibitory activity of sitafloxacin(DU-6859a)against DNA gyrase and topoisomerase IV of Streptococcus pneumoniae[J].JAntimicrob Chemother,1999,44(4):533-536.
[14]Okumura R,Hirata T,Onodera Y,et al.Dualtargeting properties of the 3-aminopyrrolidyl quinolones,DC-159a and sitafloxacin,against DNA gyrase and topoisomerase IV:contribution to reducing in vitro emergence of quinoloneresistant Streptococcus pneumoniae[J].J Antimicrob Chemother,2008,62(1):98-104.
[15]Manosuthi W,Wiboonchutikul S.Treatment outcomes of oral sitafloxacin in acute complicated urinary tract infection and pyelonephritis[J].Springerplus,2016,5(1):1-6.
[16]PMDA.日本药品与医疗器械管理局西他沙星相关申报资料.(http://www.info.pmda.go.jp/shinyaku/p200800006/430574000_22000amx00015_h100_1-h105_1.pdf).
[17]Tiengrim S,Phiboonbanakit D,Thunyaharn S,et al.Comparative in vitro activity of sitafloxacin against bacteria isolated from Thai patients with urinary tract infections and lower respiratory tract infections[J].J Med Assoc Thai,2012,95(Suppl 2):S6-S17.
[18]Milatovic D,Schmitz F J,Brisse S,et al.In vitro activities of sitafloxacin(DU-6859a)and six other fluoroquinolones against 8,796 clinical bacterial isolates[J].Antimicrob Agents Chemother,2000,44(4):1102-1107.
[19]Amano A,Matsuzaki K,Kishi N,et al.In vitro activity of sitafloxacin against clinical isolates in 2009[J].Jpn JAntibiot,2010,63(6):411-430.
[20]Schmitz F J,Fluit A C,Milatovic D,et al.In vitro potency of moxifloxacin,clinafloxacin and sitafloxacin against248 genetically defined clinical isolates of Staphylococcus aureus[J].J Antimicrob Chemother,2000,46(1):109-113.
[21]Ackermann G,Tang Y J,Rodloff A C,et al.In vitro activity of sitafloxacin against Clostridium difficile[J].J Antimicrob Chemother,2001,47(5):722-724.
[22]张倢.新型喹诺酮类抗菌药西他沙星注射剂临床前初步研究[D].苏州:苏州大学,2014.
[2]柴芸,刘明亮.新氟喹诺酮类抗菌药西他沙星[J].国外医药抗生素分册,2009,30(6):264-270.
[3]田秋月.喹诺酮类药物的研究进展[J].当代化工,2014,43(7):1283-1289.
[4]雷妮,高嵩,陈卫东,等.西他沙星的药理和临床评价[J].中国临床研究,2010,23(10):930-932.
[5]李雪,游雪甫,杨信怡.西他沙星药理研究与临床应用新进展[J].中国抗生素杂志,2013,38(12):893-900.
[6]赵苗.西他沙星片的人体药代动力学及药代动力学/药效学研究[D].上海:复旦大学,2014.
[7]徐叔云,卞如濂,陈修.药理实验方法学(第三版)[M].北京:人民卫生出版社,2002:1664-1666.
[8]孙瑞元.定量药理学[M].北京:人民卫生出版社,1987:154-229.
[9]王琪,康子胜,李家泰.国产盐酸加替沙星对感染小鼠败血症的体内抗菌作用[J].中国抗生素杂志,2001,26(3):208-214.
[10]Sano C,Tatano Y,Shimizu T,et al.Comparative in vitro and in vivo antimicrobial activities of sitafloxacin,gatifloxacin and moxifloxacin against Mycobacterium avium[J].In J Antimicrob Ag,2011,37(4):296-301.
[11]Tanaka M,Onodera Y,Uchida Y,et al.Inhibitory activities of quinolones against DNA gyrase and topoisomerase IVpurified from Staphylococcus aureus[J].Antimicrob Agents Chemother,1997,41(11):2362-2366.
[12]Ping Wu,Laura E L,Kenneth L D,et al.Mechanismofaction of the Des-F(6)quinolone BMS-284756 measured by supercoiling inhibition and cleavablecom-plex assays[J].Antimicorb Agents Chemother,2001,45(14):3660.
[13]Onodera Y,Uchida Y,Tanaka M,et al.Dual inhibitory activity of sitafloxacin(DU-6859a)against DNA gyrase and topoisomerase IV of Streptococcus pneumoniae[J].JAntimicrob Chemother,1999,44(4):533-536.
[14]Okumura R,Hirata T,Onodera Y,et al.Dualtargeting properties of the 3-aminopyrrolidyl quinolones,DC-159a and sitafloxacin,against DNA gyrase and topoisomerase IV:contribution to reducing in vitro emergence of quinoloneresistant Streptococcus pneumoniae[J].J Antimicrob Chemother,2008,62(1):98-104.
[15]Manosuthi W,Wiboonchutikul S.Treatment outcomes of oral sitafloxacin in acute complicated urinary tract infection and pyelonephritis[J].Springerplus,2016,5(1):1-6.
[16]PMDA.日本药品与医疗器械管理局西他沙星相关申报资料.(http://www.info.pmda.go.jp/shinyaku/p200800006/430574000_22000amx00015_h100_1-h105_1.pdf).
[17]Tiengrim S,Phiboonbanakit D,Thunyaharn S,et al.Comparative in vitro activity of sitafloxacin against bacteria isolated from Thai patients with urinary tract infections and lower respiratory tract infections[J].J Med Assoc Thai,2012,95(Suppl 2):S6-S17.
[18]Milatovic D,Schmitz F J,Brisse S,et al.In vitro activities of sitafloxacin(DU-6859a)and six other fluoroquinolones against 8,796 clinical bacterial isolates[J].Antimicrob Agents Chemother,2000,44(4):1102-1107.
[19]Amano A,Matsuzaki K,Kishi N,et al.In vitro activity of sitafloxacin against clinical isolates in 2009[J].Jpn JAntibiot,2010,63(6):411-430.
[20]Schmitz F J,Fluit A C,Milatovic D,et al.In vitro potency of moxifloxacin,clinafloxacin and sitafloxacin against248 genetically defined clinical isolates of Staphylococcus aureus[J].J Antimicrob Chemother,2000,46(1):109-113.
[21]Ackermann G,Tang Y J,Rodloff A C,et al.In vitro activity of sitafloxacin against Clostridium difficile[J].J Antimicrob Chemother,2001,47(5):722-724.
[22]张倢.新型喹诺酮类抗菌药西他沙星注射剂临床前初步研究[D].苏州:苏州大学,2014.