Doripenem 用 於 老 年 泌 尿 道 感 染 療 效 秀 傳 紀 念 醫 院 藥 劑 科 藥 師 黃 美 嫆 秀 傳 紀 念 醫 院 醫 師 汪 忠 炫 摘 要 Gram(-) carbapenam -doripenem (doripenem vs. levofloxacin) 2010 102011 12 65 doripenem 3 170 doripenem levofloxacin 2010 102011 1265 55 doripenem 128 levofloxacin SPSS 17.0 doripenem 121 71.2% (121/170) doripenem white blood cell (WBC) C-reactive protein (CRP) doripenem (n=55) levofloxacin (n=128) 85.5% 97.6% Escherichia coli Escherichia coli (ESBL) doripenem 71.2% 85.5% Gram(-) doripenem urinary tract infections doripenem levofloxacin Gram(-) bacilli Escherichia coli Pseudomonas aeruginosa 壹 前 言 1993 65 7%201165 10.9% 25372.2% 1 62 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.4 Dec. 31 2013
Doripenem 2012 2 77.0% MRSA (methicillinresistant Staphylococcus aureus) 65.2% CRAB (carbapenem resistant Acinetobacter baumannii) 18.1% CRPA (crabapenemresistant Pseudomonas aeruginosa) 22.9% VRE (vancomycin resistant enterococc) 10.7% CRKP (carbapenem-resistant Klebsiella pneumoniae) 78.3% MRSA 68.9% CRAB 15.5% CRPA 15.8% VRE 9.6% CRKP 3 (extended-spectrum beta-lactamase ESBL) Escherichia coli Klebsiella pneumonia 33.3% 46.7% MRSA Pseudomonas aeruginosa Enterbacteriaceae Acinetobacter baumannii 25% 30% 4 100 5 ( ) (Escherichia coli) Pseudomonas aeruginosa Proteus mirabilis Klebsiella pneumoniae 6 () nitrofurantion cephalosporins trimethoprim/ sulfamethoxazole fluoroquinolones fluoroquinolones ampicillin/sulbactam amoxicillin/ clavulanate cephalosporins a m i n o g l y c o s i d e cephalosporins fluoroquinolones amoxicillin/clavulanate aminoglycoside impenem meropenem 7-10 10-14 10-14 (CDC) 2013 3(Vital Signs) 7 (Carbapenem-resistant Enterobacteriaceae (CRE)) (carbapenem) Doripenem 294 Dec. 31 2013 藥 學 雜 誌 第 117 冊 63
2007 (FDA) 8 doripenem (doripenem vs. levofloxacin) Gram(-) 貳 研 究 對 象 與 方 法 doripenem 2010 102011 12 doripenem 65 doripenem (1) (2) (3) (4) (5) (6) 3170 ( d o r i p e n e m v s. levofloxacin) 2010 102011 12 (ICD-9- CM 5990) ICD-9-CM 5990 doripenem levofloxacin 65 355 doripenem 128 levofloxacin SPSS 17.0 P < 0.05 參 結 果 79.4 7.6 3.7 doripenem IV infusion > 1 hours (fever) 37.2 2.8 ( ) WBC (white blood cell) 15849.7 9411.7 (/ul) CRP (C-reactive protein) 12.0 9.7 (mg/dl) Seg (segmented neutrophil) 80.6 13.3 (%)9.3 4.9162 (95.3%) 8 (4.7%) doripenem 57 () 57 () 170 doripenem 121 71.2% 49 28.8% doripenem fever WBC CRP Seg () Doripenem WBC CRP P (0.002; 0.000) doripenem () 表 一 170 位 病 人 基 本 特 徵 (n=170) (%) 84 (49.4) 86 (50.6) ( ) 79.4 7.6 ICU (doripenem) 3.7 5.6 Fever ( ) 37.2 2.8 WBC (/ul) 15849.7 9411.7 CRP (mg/dl) 12.0 9.7 Seg (%) 80.6 13.3 ( ) 9.3 4.9 8 (4.7) 162 (95.3) () 57 (33.5) 57 (33.5) 64 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.4 Dec. 31 2013
Doripenem () 26 (15.3) 9 (5.3) () 6 (3.5) 3 (1.8) 12 (7.0) ICU WBC white blood cell count CRP C-reactive protein Seg segmented neutrophil 表 二 比 較 ( 存 活 vs. 死 亡 ) 病 人 基 本 特 徵 (n=170) (n=121,71.2%) (n=49,28.8%) P value ( ) 79.3 8.3 79.0 7.8 0.818 ( ) 83 25 0.791 ICU 3.3 4.8 4.6 7.3 0.199 Fever ( ) 37.6 0.9 37.3 0.9 0.232 WBC (/ul) 15976.9 9315.0 15515.3 9847.0 0.774 CRP (mg/dl) 12.1 9.8 12.0 9.7 0.951 Seg (%) 80.5 13.8 80.5 12.8 0.976 ( ) 9.6 4.9 8.8 5.0 0.369 19 (15.7%) 10 (20.4%) 0.066 1.5 0.6 1.5 0.7 0.318 表 三 分 析 doripenem 治 療 前 後 病 人 的 臨 床 表 徵 及 生 化 值 Patients (n=170) Normal Before After P value Fever ( ) < 37.2 37.2 2.9 37.2 0.7 0.946 WBC (/ul) 4.5-11 10 3 /ul 15843.8 9444.3 12742.2 9137.4 0.002* CRP (mg/dl) < 0.3 mg/dl 12.1 9.8 7.4 1 1.0 0.000* *P- value <0.05 is statistically significant Doripenem 162 (95.3%) 179 (multidrug-resistant Acinetobacter baumannii MDRAB) 36 (20.1%) (G(+) coccus) 28 (15.6%) Escherichia coli (ESBL) Klebsiella pneumoniae (ESBL) 8.9% 5.6% Doripenem 50 G(-) bacillus 51 MDRAB () 表 四 分 析 doripenem 治 療 前 162 位 病 人 的 菌 種 報 告 (%), B=179 MDRAB 36 (20.1) G(+) coccus 34 (19.0) Other G(-) bacillus 27 (15.1) Escherichia coli 19 (10.6) Escherichia coli (ESBL) 16 (8.9) Pseudomonas aeruginosa 15 (8.4) Klebsiella pneumoniae 13 (7.3) Klebsiella pneumoniae (ESBL) 10 (5.6) Acinetobacter baumannii 9 (5.0) doripenem 162 61 G(-) bacillus 50 51 MDRAB 26 Acinetobacter baumannii 9 Stenotrophomonas maltophilia 5 Other G(-) bacillus 4 G(+) coccus 3 Pseudomonas aeruginosa 2 Escherichia coli (ESBL) 1 VRE `1 MDRAB multidrug-resistant Acinetobacter baumannii ESBL extended-spectrum -lactamases VRE vancomycine-resistant enterococcus faecium B bacterial strains Doripenem levofloxacin 82.5 7.780.5 10.0 19 (34.6%) 26 (20.3%) WBC 15830.9 8458.4 (/ul) 11952.8 4969.0 (/ ul) CRP 10.4 8.0 (mg/dl) 9.6 8.3 (mg/dl) PCT (procalcitonin,ng/ ml) 24.5 63.1 (ng/ml) 2.4 4.5 (ng/ml) 11.1 7.06.1 3.4 294 Dec. 31 2013 藥 學 雜 誌 第 117 冊 65
85.5% 97.6% WBC PCT P (0.002;0.050;0.000) doripenem doripenem levofloxacin Escherichia coli Escherichia coli (ESBL) () 表 五 Doripenem vs. Levofloxacin 病 人 基 本 特 徵 Doripenem (n=55) (85.5%) Levofloxacin (n=128) (97.6%) ( ) 82.5 7.7 80.5 10.0 0.183 ( ) 19 (34.6%) 26 (20.3%) 0.677 WBC (/ul) 15830.9 8458.4 11952.8 4969.0 0.002* CRP (mg/dl) 10.4 8.0 9.6 8.3 0.596 Seg (%) 80.7 11.1 80.7 9.5 0.982 PCT (ng/ml) 24.5 63.1 2.4 4.5 0.050 (%) 20 (36.3%) 41 (32.0%) 0.516 ( ) 11.1 7.0 6.1 3.4 0.000* (Doripenem vs. Levofloxacin ) 21/55 (38.2%) 33/128 (25.8%) Doripenem,B=29 Levofloxacin,B=77 Escherichia coli 9 (31.0) 23 (29.8) Escherichia coli (ESBL) 6 (20.6) 16 (20.7) Other G(-) bacillus 5 (17.0) 15 (19.4) Pseudomonas aeruginosa 2 (6.8) 10 (12.9) Klebsiella pneumoniae 1 (3.4) 5 (6.4) Streptoccus group D 3 (10.3) 4 (5.1) K. pneumoniae (ESBL) 2 (6.8) 3 (3.8) Enterococcus faecalis 1 (3.4) 1 (1.2) PCT procalcitonin P value 肆 討 論 Doripenem 2007 (FDA) doripenem doripenem hydrate () doripenem ( ) 170 doripenem 71.2% doripenem MDRAB 20.1% 2010 58.7% (Acinetobacter baumannii) 20021.3% 2010 41% 66 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.4 Dec. 31 2013
Doripenem 10 doripenem 500 mg levofloxacin 250 mg Doripenem levofloxacin 82.1% 83.4% 95.1% 90.2% fluoroquinolones doripenem 9 cephalosporins fluoroquinolones piperacillin/tazobactom crabapenem 10,11 Enterbacteriaceae Pseudomonas aeruginosa Escherichia coli (ESBL) 20% Doripenem levofloxacin WBC PCT P (0.002 0.050) doripenem WBC 15830.9 (/ul) PCT 24.5 (mg/dl) doripenem Doripenem 12-14 carbapenems valproic acid probenecid doripenem doripenem 13-15 doripenem 11-13,15 伍 結 論 Gram(-) Pseudomonas aeruginosa (Enterbacteriaceae) (Acinetobacter) -lactamase Enterbacteriaceae Gram(-) doripenem 參 考 資 料 : 1. 2011 12 2. 2011 2012 22 301-307. 3. 2005 1(2) 65-78. 4. Richards Chesley L. Urinary Tract Infections in the frail elderly: issues for diagnosis, treatment and prevention. Int Urol Nephrol. 2004; 36(3): 457-63. 5. 1 0 0 2011 6. Centers for Disease Control, R.O.C (Taiwan): Guidelines for antimicrobial therapy of urinary tract infections in Taiwan. Microbiol Immunol Infect. 2000; 33: 271-272. 7. CDC-Carbapenem-resistant Enterobacteriaceae -HAI http://www.cdc.gov/hai/organisms/cre/ 8. FDA approves new drug to treat complicated urinary tract and intra-abdominal infections. Available at:www.fda. gov/bbs/topics/news/2007/new01728.html. Accessed December 10, 2007 9. Naber K. G, L. Llorens, K. Kaniga, et al: Intravenous doripenem 500 mg versus levofloxacin 250 mg,with an option to switch to oraltherapy for the treatment of complicated lower urinarytract infection and pyelonephritis. Antimic Agent Chemother.2009; 53; 3782-92. 10. Hagerman JK, Knechtel SA, Klepser ME. Doripenem: A new extended-spectrum carbapenem antibiotic. Formul 2007; 42: 676-688. 11. Matthews SJ, Lancaster JW. Doripenem monohydrate, a broad-spectrum carbapenem antibiotic. Clinical therapeutics 2009; 31: 42-63. 12. Hussar DA. New Drugs: Doripenem, raltegravir, and ixabepilone. Journal of the American Pharmacists Association 2008; 48: 108-11. 13. Cada DJ, Levien TL, Mistry B, Baker DE. Formulary Drug Reviews-Doripenem for Injection. Hospital Pharmacy 2008; 43: 210-21. 14. Editorial : Doripenem (doribax)--a new parenteral carbapenem.med Lett Drugs Ther. 2008; 50: 5-7. 15. Pharmaceutical OMN. Doribax (doripenem) package insert, Ortho-McNeil Pharmaceutical. Raritan (NJ) 2007. 294 Dec. 31 2013 藥 學 雜 誌 第 117 冊 67
Efficacy of Doripenem in the Elderly with Urinary Tract Infections Mei-Jung Huang 1, Chung-Hsuan Wang 2 Department of Pharmacy 1, Department of Emergency Medicine 2 Show Chwan Memorial Hospital Abstract Urinary tract infection is one of the most common infections in the elderly, for which the most common pathogen is Escherichia coli. As antibiotic resistance getting increasing, it becomes progressively more difficult to treat these common Gram (-) bacteria, hindering physicians from effectively choosing antibiotics to treat them. The aim of this study is to investigate the safety and efficacy of using a new carbapenem doripenem to treat refractory infections in the Intensive Care Unit (ICU) retrospectively, and to facilitate the doctors' decision making process by comparing the success rates between doripenem and levofloxacin for treating urinary tract infections (UTI) in the elderly. Totally 170 patients over the age of 65 who infections which were treated with doripenem in the ICU for over three days from October 2010 to December 2011 were reviewed. In order to compare the effectiveness of doripenem and levofloxacin for treatment of UTI in the elderly, during the same period of time, 55 elderly patients treated with doripenem and 128 elderly patients treated with levofloxacin were included for evaluation. SPSS 17.0 was used for statistical analysis. Result: among the 170 ICU cases of infections treated with doripenem, 121 patients became stable, and were transferred to general wards, resulting in a survival rate of 71.2%. After treatment with doripenem, both the patients' white blood cell count (WBC) and C - reactive protein (CRP) show improved with statistical significance. In cases of diagnostic UTI, the survival rates in doripenem group (n=55) was 85.5%, while in levofloxacin group (n=128) was 97.6%. The most prevalent microorganisms isolated from UTI patients in this study were Escherichia coli and Escherichia coli (ESBL). In summary, our studies have shown that for all infections vs. UTI treated with doripenem survival rates are 71.2% and 85.5%, respectively. Clinically, if a refractory infection in the elderly is suspected to be caused by Gram (-) bacteria, the new drug doripenem might be an alternative choice of antibiotic. 68 THE JOURNAL OF TAIWAN PHARMACY Vol.29 No.4 Dec. 31 2013