Dec. 2012 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 365 11 sita oxacin 1 1 1 1 1 1 2 2 3 3 1 1 1 2 3 2012 9 14 sita oxacin STFX 50 mg 10% 2008 1 2008 12 2010 11 2 STFX 1,452 91.4% 1,235/1,351 95.9% 466/486 87.2% 511/586 96.1% 49/51 93.5% 145/155 87.7% 64/73 86.0% 49/57 77.4% 48/62 90.5% 545/602 Escherichia coli 92.7% 294/317 Enterococcus faecalis 86.0% 43/50 Pseudomonas aeruginosa 66.7% 16/24 Klebsiella pneumoniae 95.2% 20/21 Chlamydia trachomatis 88.9% 8/9 2.71% 37/1,365 0.88% 12 0.51% 7 1 STFX 91.4% 87.2% Sita oxacin STFX 2008 1 6 STFX
366 12 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 Dec. 2012 1 8 DNA 2,3 16 12 20 171 2008 12 2010 11 2 3,558 4.44% 1.65% 1.17% 90% 9 Escherichia coli - Extended-Spectrum Beta-Lactamase: ESBL STFX E. coli 2,3,10 70% 11 1,452 STFX I 1. 50 mg 1 STFX 50 mg 10% 1 g STFX 100 mg 2. 2008 12 1 2010 11 30 STFX 3,558 1,452 3. 7 FAX 4. 1 1 5. 1 12 6. 1 100 %
Dec. 2012 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 367 13 100 % 1 12 3 2 100 % ICH MedDRA/J: Medical Dictionary for Regulatory Activities/J Ver. 14.0 Fig. 1. Distribution of the patients in the study.
368 14 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 Dec. 2012 Table 1. Patients demographics.
Dec. 2012 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 369 15 II 1. STFX 3,558 1,452 1,341 92.4% 62 4.3% 49 3.4% 87 1,365 14 1,351 Fig. 1 2 1,351 Table 1 1 69.6% 59.6 19.3 SD 71.2 12.8 10 65 47.7% 78.2% 3.3% 8.9% 30.0% 88.2% 1 50 mg 1 2 90% 1 100 mg 1 2 6.4% 8.2% 6.3 2.5 SD 8.5 5.9 2 2 60.6% 50.9 19.0 SD 62.6 15.0 65 27.5% 48.4% 23.5% 33.5% 31.4% 86.5% 44.5% 1 50 mg 1 2 96.1% 91.0% 1 100 mg 1 2 2.0% 5.2% 7.5 2.6 SD 8.6 5.9 1 3 98.6% 45.5 20.5 SD 1 50 mg 1 2 86.3% 1 100 mg 1 2 9.6% 9.3 5.8 SD 3 1 1 1,351 91.4% 1,235/1,351 Table 2 95.9% 466/486 87.2% 511/586 96.1% 49/51 93.5% 145/155 87.7% 64/73 2 86.3% 352/408 89.3% 159/178 Table 2 65 65 75
370 16 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 Dec. 2012 Table 2. Clinical ef cacy by patient demographics.
Dec. 2012 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 371 17 75 95% 65 90.6% 116/128 65 75 84.7% 150/177 75 87.2% 245/281 Table 2 97.3% 142/146 86.3% 446/517 94.7% 89/94 91.8% 56/61 Table 2 65 94.6% 35/37 65 100.0% 14/14 65 93.8% 75/80 65 75 97.2% 35/36 75 89.7% 35/39 93.8% 15/16 93.3% 125/134 65 85.5% 47/55 65 75 100.0% 5/5 75 92.3% 12/13 Table 2 96.0% 24/25 3 1,351 143 10.6% 83.2% 119/143 Table 2 62 57 77.4% 48/62 86.0% 49/57 2 1 602 Table 3 Escherichia coli E. coli 52.7% Enterococcus 12.0% Staphylococcus 11.3% Streptococcus 7.5% Klebsiella 5.0% Pseudomonas aeruginosa P. aeruginosa 4.0% E. coli 70.5% 10% E. coli 35.6% Enterococcus 17.2% Staphylococcus 14.6% Streptococcus 11.3% E. coli 83.3% E. coli 45.0% Enterococcus Staphylococcus 13.3% P. aeruginosa 11.7% 52.9% Chlamydia trachomatis C. trachomatis 2 90.5% 545/602 Table 4 E. coli 92.7% 294/317 Enterococcus faecalis E. faecalis 86.0% 43/50 P. aeruginosa 66.7% 16/24 Klebsiella pneumoniae K. pneumoniae 95.2% 20/21 C. trachomatis 88.9% 8/9 96.3% 258/268 85.4% 204/239 94.4% 17/18 83.3% 50/60 94.1% 16/17 E. coli 96.3% 182/189 85.9% 73/85 93.3% 14/15 88.9% 24/27
372 18 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 Dec. 2012 Table 3. Distribution of causative bacteria.
Dec. 2012 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 373 19 Table 4. Bacterial eradication rate.
374 20 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 Dec. 2012 Table 5. Bacterial eradication rate complicated cystitis.
Dec. 2012 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 375 21 Table 6. Incidence of adverse drug reactions ADRs.
376 22 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 Dec. 2012 3 STFX 83.1% 148/178 92.9% 26/28 90.9% 30/33 E. coli 81.3% 52/64 100.0% 13/13 100.0% 8/8 Table 5 C. trachomatis 88.9% 8/9 Neisseria gonorrhoeae STFX 6 Table 4 4 1,365 37 39 2.71% Table 6 12 0.88% 7 0.51% 1 79 1 50 mg 1 2 4 9 6 1 5 12 2 12 1 11 8 STFX 3 1 11 QT 1.64% 8/489 2.70% 16/593 7.69% 4/52 3.85% 6/156 4.00% 3/75 65 2.49% 14/562 65 75 3.00% 10/333 75 2.77% 13/470 Table 7 1 50 mg 1 2 2.90% 36/1,241 100 mg 1 2 1.04% 1/96 28 III E. coli levo oxacin LVFX MIC 2 g/ml 2000 91.9% 2010 70.7% MIC 90 0.5 g/ml 16 g/ml 4 7, 13 STFX E. coli 2,3,10 70%
Dec. 2012 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 377 23 Table 7. Incidence of ADRs by age. 11 STFX 2008 12 2010 11 STFX 3,558 9 1,452 91.4% 1,235/1,351 87% 94.8% 95.5% 88.6% 14 E. coli 70.5% 83.3% 15 17 E. coli 70 80% E. coli 96.3% 182/189 93.3% 14/15 E. coli E. faecalis P. aeruginosa K. pneumoniae Staphylococcus 15 17 15 17 STFX E. coli 85% 83% UTI 4 18
378 24 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 Dec. 2012 12 MATSUMOTO E. coli 19 MATSUMOTO STFX 77.4% 48/62 E. coli DNA quinolone-resistance determining region: QRDR 1 2 LVFX, cipro oxacin, tosu oxacin 2,3 QRDR 3 E. coli LVFX MIC 2.0 g/ml 2.1% 4/193 STFX MIC 1.0 g/ ml 65.8% 127/193 10 STFX 2.71% 37/1,365 0.88% 12 0.51% 7 4.44% 1.65% 1.17% 9 1 STFX STFX 91.4% 87.2% Sita oxacin 1 SATO, K.; K. HOSHINO, M. TANAKA, et al.: Antimicrobial activity of DU-6859, a new potent uoroquinolone, against clinical isolates. Antimicrob. Agents Chemother. 36: 1491 1498, 1992 2 Sita oxacin 56 S-1 : 1 17, 2008 3 133: 43 51, 2009 4 2002 52 11,475 Jpn. J. Antibiotics 58: 17 44, 2005 5 2004 77 18,639 Jpn. J. Antibiotics 59: 428 451, 2006 6 2007 72 12,919 Jpn. J. Antibiotics 62: 346 370, 2009 7 2010 72 12,866 Jpn. J. Antibiotics 65: 181 206, 2012 8 2009 Sita oxacin Jpn. J. Antibiotics 63: 411 430, 2010 9
Dec. 2012 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 379 25 sita oxacin Jpn. J. Antibiotics 64: 319 337, 2011 10 58: 466 482, 2010 11 NAKASHIMA, M.; T. UEMATSU, K. KOSUGE, et al.: Pharmacokinetics and tolerance of DU-6859a, a new uoroquinolone, after single and multiple oral doses in healthy volunteers. Antimicrob. Agents Chemother. 39: 170 174, 1995 12 1 57: 511 525, 2009 13 2000 37 8,474 Jpn. J. Antibiotics 56: 341 364, 2003 14 50 mg 10% 2012 7 7 15 29: 227 234, 2004 16 102: 878 883, 2008 17 25: 29 39, 2009 18 UTI 4 45: 203 247, 1997 19 MATSUMOTO, T.; R. HAMASUNA, K. ISHIKAWA, et al.: Nationwide survey of antibacterial activity against clinical isolates from urinary tract infections in Japan 2008. Int. J. Antimicrob. Agents 37: 210 218, 2011 Ef cacy and safety of sita oxacin in patients with urinary tract infections TAKUYUKI MATSUMOTO 1, HIROKI YAMAGUCHI 1, KAZUHIRO UCHINO 1, MEGUMI TAKAHASHI 1, HIROKO KODAMA 1, SATOKO HAMAJIMA 1, RIE YONEMOCHI 2, SACHIKO FUJITA 2, ATSUSHI TAKITA 3, NAOKI YAMANOUCHI 3, TOMOO SHIOZAWA 1 and YUKIHIRO OKUTANI 1 1 Post Marketing Studies Management Department, Daiichi Sankyo Company, Limited 2 Pharmacovigilance Department, Daiichi Sankyo Company, Limited 3 Clinical Data and Biostatistics Department, Daiichi Sankyo Company, Limited Sita oxacin STFX, Gracevit 50 mg, ne granules 10%, a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was carried out over the 2 years between December 2008 and November 2010. We studied the ef cacy and safety of STFX in 1,452 patients with urinary tract infections cystitis, pyelonephritis, urethritis. The total efficacy rate for urinary tract infections was 91.4% 1,235/1,351 patients. Ef cacy rates, classi ed by the type of infection, were: uncomplicated cystitis 95.9% 466/486
380 26 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 Dec. 2012 patients, complicated cystitis 87.2% 511/586 patients, uncomplicated pyelonephritis 96.1% 49/51 patients, complicated pyelonephritis 93.5% 145/155 patients, and urethritis 87.7% 64/73 patients. Ef cacy rates were 86.0% 49/57 patients for non-responders to cephems and 77.4% 48/62 patients for non-responders to quinolones. The eradication rate of indicated strains was 90.5% 545/602 strains. The eradication rates of major causative bacteria were; Escherichia coli 92.7% 294/317 isolates, Enterococcus faecalis 86.0% 43/50 isolates, Pseudomonas aeruginosa 66.7% 16/24 isolates, Klebsiella pneumoniae 95.2% 20/21 isolates, and Chlamydia trachomatis 88.9% 8/9 isolates. The incidence of adverse drug reactions ADRs was 2.71% 37/1,365 cases. Major ADRs were diarrhoea 0.88%, 12 cases and hepatic function disorders 0.51%, 7 cases. A serious ADR hepatic function abnormality was observed in 1 case, and the hepatic function in this patient returned to normal after treatment with STFX was discontinued. In conclusion, these results suggest that STFX is a useful antibacterial agent with an ef cacy rate of 91.4% against urinary tract infections, with a minimum ef cacy rate of 87.2% against complicated cystitis, and has no serious problems in its safety pro le.