产碳青霉烯酶肺炎克雷伯菌的治疗ppt课件

桂林医学院附属医院 替加环素能否用于产碳青酶烯酶肺 炎克雷伯菌（CRKP）的严重感染 桂林市中医医院桂林市中医医院 桂林医学院附属医院 微生物中的“收藏家” 虽然不是对抗 生素天然耐药 ，但因为只产 适量的青霉素 酶染色体，被 称为臭名昭著 的“多耐药质 粒的收藏家” 肺炎克雷伯菌 D类碳 青霉烯 酶 B类碳 青霉烯 酶 A类碳 青霉烯 酶 桂林医学院附属医院 耐药质 粒编码 KPC GES VIM IMP NDM OXA 桂林医学院附属医院 耐药进程 氨基糖苷类 内酰胺类 氟喹诺酮类 碳青霉烯类 桂林医学院附属医院 泛耐药CRKP 临床使用经验有限 因广泛使用，耐药菌株已 出现 Polymyxins 多粘霉素 ？ Fosfomycin 磷霉素 Tigecycline 替加环素 桂林医学院附属医院 Clinical studies, antimicrobial therapies, and outcomes for patients infected with KPC-producing K. pneumoniae ReferenceCountry (yr of publication) Study designNo. of patients with indicated infection Type of - lactamase (no. of isolates) Treatment with active drug (no. of patients) Outcome (no. of successes/no. of failures) 182USA (2009)Case series3 BSIsKPC-2 (3)Tetracycline- aminoglycoside (1) 1/0 Colistin (3)1/2 175Greece (2010)Case-control study 19 BSIsKPC-2 (19)Colistin (10)2/8 162China (2008)Tigecycline- aminoglycoside (1) 1/0 Colistin- aminoglycoside (9) 4/5 274Greece (2011)Case-control study 53 BSIsKPC-2 (53)Carbapenem (1) 0/1 Colistin (7)3/4 Tigecycline (5)3/2 Aminoglycoside (2) 2/0 Colistin- aminoglycoside (2) 2/0 桂林医学院附属医院 Clinical studies, antimicrobial therapies, and outcomes for patients infected with ML-producing K. pneumoniae ReferenceCountry (yr of publication) Study designNo. of patients with indicated type of infection Type of MBL (no. of isolates) Treatment (no. of patients) Outcome (no. of successes/no. of failures) 86Greece (2008)Tigecycline (1)1/0 56Spain (2008)Tigecycline- colistin (2) 1/1 269Taiwan (2001)Case series3 BSIsIMP-8 (3)Carbapenem (3) 1/2 143Taiwan (2004)Case series3 (2 pneumonias, 1 BSI) IMP-type enzyme (3) Carbapenem (1) 1/0 240Greece (2008)Case series17 (14 BSIs, 3 pneumonias) VIM-1 (17)Colistin (6)6/0 Tigecycline (1)0/1 175Greece (2010)Case-control study 18 BSIsVIM-1 (17)Colistin (10)6/4 VIM-type enzyme (1) Colistin- aminoglycoside (8) 4/4 67Greece (2009)Prospective observational study 67 BSIsVIM-1 (67)Carbapenem (14) 11/3 Carbapenem- colistin (8) 8/0 Colistin (15)11/4 No active drug (18) 13/5 桂林医学院附属医院 Regimen A, combination therapy with 2 active drugs, one of which was a carbapenem; regimen B, combination therapy with 2 active drugs, not including a carbapenem; regimen C, monotherapy with an aminoglycoside; regimen D, monotherapy with a carbapenem; regimen E, monotherapy with tigecycline; regimen F, monotherapy with colistin; regimen G, inappropriate therapy. Regimen A was superior to regimens B, E, F, and G (for A versus B, E, F, and G, the Pvalue was 0.02, 0.03, 0.0001, and 0.0001, respectively). Regimens B, C, and D were superior to regimen G (for B versus G, P = 0.014; for C versus G, P = 0.04; and for D versus G, P = 0.03). 桂林医学院附属医院 分析 The decreased clinical effectiveness of tigecycline in severe infections could be attributed partly to the pharmacokinetic/pharmacodynamic (PK/PD) profile of the drug. 替加环素在严重感染中的临床疗效减少，可能是 由于药物的PK/PD PK/PD：对不同类抗菌药物给药方案具有指导意义 桂林医学院附属医院 Tigecycline demonstrates mainly bacteriostatic activity against Gram-negative organisms, and the attainable drug concentrations at several anatomic sites are suboptimal. 替加环素对革兰氏阴性菌主要是抑菌效果 the attainable drug concentrations at several anatomic sites are suboptimal 在体外药效学模式中，随着浓度超过1mg/L时，其 抑菌作用保持不变，因此 实现药物浓度是次重要 的 桂林医学院附属医院 The peak serum concentrations achieved with the standard dosing regimen of the drug (50 mg twice daily) range from 0.6 to 0.9 g/ml while those attained in the urine and in the epithelial lining fluid are severalfold lower 按照替加环素的标准给药方案（50mg q12） 当血药浓度达到峰值时（ 0.6 to 0.9 g/ml ） ，其尿液和上皮表面液体中的浓度则非常低 桂林医学院附属医院 The drug concentrations attainable by this standard dosing regimen, combined with this drugs MIC profile for current CPE isolates, render it unlikely for tigecycline to cure CPE infections at anatomic sites where drug concentrations are suboptimal. 替加环素在某些部位浓度很低，且不足以达到抑 菌浓度。当CPE感染在这些部位时，则很难达到疗 效。 这使得替加环素不太可能治愈CPE在这些部位的严 重感染 桂林医学院附属医院 结论 Therefore, this drug should be used with caution against CPE, preferentially in combination with another active agent and after due consideration of the attainable drug concentration at the anatomic site of infection and of the MIC for the infecting organism. 因此，替加环素在对待产碳青霉烯酶肠杆菌（CPE ）时须谨慎使用。 综合考虑替加环素在感染部位的浓度以及其最低 抑菌浓度 优先结合另一个活性药物。 桂林医学院附属医院 谢谢聆听！谢谢聆听！谢谢聆听！谢谢聆听！ 桂林医学院附属医院 参考文献 产碳青霉烯酶肺炎克雷伯菌的耐药基因及流行病学研究进 展 Carbapenemases in Klebsiel