产碳青霉烯酶肺炎克雷伯菌治疗
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• 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
9
• Tigecycline demonstrates mainly bacteriostatic activity against Gram-negative organisms, and the attainable drug concentrations at several anatomic sites are suboptimal.
monotherapy with an aminoglycoside; regimen D, monotherapy with a carbapenem; regimen E, monotherapy with tigecycline; regimen F, monotherapy with colistin; regimen G, inappropriate
17 (14 BSIs, 3 pneumonias)
IMP-type enzyme (3)
VIM-1 (17)
Carbapenem (1) 1/0
Colistin (6)
6/0
Tigecycline (1)
0/1
18 BSIs
VIM-1 (17)
Colistin (10)
6/4
67 BSIs
VIM-type enzyme (1)
Reference 86 56 269 143 240
175
67
Country (yr of publication)
Greece (2008) Spain (2008)
Taiwan (2001) Taiwan (2004)
Greece (2008)
Study design
Case series Case series Case series
• 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 μg/ml ），其
尿液和上皮表面液体中的浓度则非常低
11
• The drug concentrations attainable by this standard dosing regimen, combined with this drug's MIC profile for current CPE isolates, render it unlikely for tigecycline to cure CPE infections at anatomic sites where drug concentrations are suboptimal.
of isolates)
of patients)
Tigecycline (1)
Outcome (no. of successes/no. of failures)
1/0
3 BSIs
IMP-8 (3)
Tigecycline-
1/1
colistin (2)
Carbapenem (3) 1/2
3 (2 pneumonias, 1 BSI)
VIM-1 (67)
Colistin-
4/4
aminoglycoside
(8)
Carbapenem (14) 11/3
Carbapenem-
ຫໍສະໝຸດ Baidu
8/0
colistin (8)
Colistin (15)
11/4
No active drug 13/5 (18)
7
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,
Colistin (3)
KPC-2 (19)
Colistin (10)
Outcome (no. of successes/no. of failures) 1/0
1/2
2/8
53 BSIs
KPC-2 (53)
Tigecycline-
1/0
aminoglycoside
(1)
Colistin-
4/5
aminoglycoside
Greece (2010)
Case-control study
Greece (2009)
Prospective observational study
No. of patients with indicated type of infection
Type of MBL (no. Treatment (no.
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
1
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”
2
3
耐药进程
4
泛耐药CRKP
5
Clinical studies, antimicrobial therapies, and outcomes for patients infected with KPC-producing K. pneumoniae
• Colistin-Resistant, Klebsiella pneumoniae Carbapenemase (KPC)–ProducingKlebsiella pneumoniae Belonging to the International Epidemic Clone ST258
15
• 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
10
• 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。
13
谢谢聆听！
14
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 Klebsiella pneumoniae and Other Enterobacteriaceae: an Evolving Crisis of Global Dimensions
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
• 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
12
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.
G, P = 0.03).
8
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.
Reference 182
175 162
274
Country (yr of publication)
USA (2009)
Study design Case series
Greece (2010) China (2008)
Case-control study
Greece (2011)
Case-control study
No. of patients with indicated infection 3 BSIs
19 BSIs
Type of βlactamase (no. of isolates)
KPC-2 (3)
Treatment with active drug (no. of patients)
Tetracyclineaminoglycoside (1)
(9)
Carbapenem (1) 0/1
Colistin (7)
3/4
Tigecycline (5)
3/2
Aminoglycoside 2/0 (2)
Colistin-
2/0
aminoglycoside
(2)
6
Clinical studies, antimicrobial therapies, and outcomes for patients infected with MβL-producing K. pneumoniae
• The peak serum concentrations achieved with the standard dosing regimen of the drug (50 mg twice daily) range from 0.6 to 0.9 μg/ml while those attained in the urine and in the epithelial lining fluid are severalfold lower
• PK/PD：对不同类抗菌药物给药方案具有指导意义
9
• Tigecycline demonstrates mainly bacteriostatic activity against Gram-negative organisms, and the attainable drug concentrations at several anatomic sites are suboptimal.
monotherapy with an aminoglycoside; regimen D, monotherapy with a carbapenem; regimen E, monotherapy with tigecycline; regimen F, monotherapy with colistin; regimen G, inappropriate
17 (14 BSIs, 3 pneumonias)
IMP-type enzyme (3)
VIM-1 (17)
Carbapenem (1) 1/0
Colistin (6)
6/0
Tigecycline (1)
0/1
18 BSIs
VIM-1 (17)
Colistin (10)
6/4
67 BSIs
VIM-type enzyme (1)
Reference 86 56 269 143 240
175
67
Country (yr of publication)
Greece (2008) Spain (2008)
Taiwan (2001) Taiwan (2004)
Greece (2008)
Study design
Case series Case series Case series
• 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 μg/ml ），其
尿液和上皮表面液体中的浓度则非常低
11
• The drug concentrations attainable by this standard dosing regimen, combined with this drug's MIC profile for current CPE isolates, render it unlikely for tigecycline to cure CPE infections at anatomic sites where drug concentrations are suboptimal.
of isolates)
of patients)
Tigecycline (1)
Outcome (no. of successes/no. of failures)
1/0
3 BSIs
IMP-8 (3)
Tigecycline-
1/1
colistin (2)
Carbapenem (3) 1/2
3 (2 pneumonias, 1 BSI)
VIM-1 (67)
Colistin-
4/4
aminoglycoside
(8)
Carbapenem (14) 11/3
Carbapenem-
ຫໍສະໝຸດ Baidu
8/0
colistin (8)
Colistin (15)
11/4
No active drug 13/5 (18)
7
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,
Colistin (3)
KPC-2 (19)
Colistin (10)
Outcome (no. of successes/no. of failures) 1/0
1/2
2/8
53 BSIs
KPC-2 (53)
Tigecycline-
1/0
aminoglycoside
(1)
Colistin-
4/5
aminoglycoside
Greece (2010)
Case-control study
Greece (2009)
Prospective observational study
No. of patients with indicated type of infection
Type of MBL (no. Treatment (no.
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
1
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”
2
3
耐药进程
4
泛耐药CRKP
5
Clinical studies, antimicrobial therapies, and outcomes for patients infected with KPC-producing K. pneumoniae
• Colistin-Resistant, Klebsiella pneumoniae Carbapenemase (KPC)–ProducingKlebsiella pneumoniae Belonging to the International Epidemic Clone ST258
15
• 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
10
• 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。
13
谢谢聆听！
14
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 Klebsiella pneumoniae and Other Enterobacteriaceae: an Evolving Crisis of Global Dimensions
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
• 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
12
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.
G, P = 0.03).
8
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.
Reference 182
175 162
274
Country (yr of publication)
USA (2009)
Study design Case series
Greece (2010) China (2008)
Case-control study
Greece (2011)
Case-control study
No. of patients with indicated infection 3 BSIs
19 BSIs
Type of βlactamase (no. of isolates)
KPC-2 (3)
Treatment with active drug (no. of patients)
Tetracyclineaminoglycoside (1)
(9)
Carbapenem (1) 0/1
Colistin (7)
3/4
Tigecycline (5)
3/2
Aminoglycoside 2/0 (2)
Colistin-
2/0
aminoglycoside
(2)
6
Clinical studies, antimicrobial therapies, and outcomes for patients infected with MβL-producing K. pneumoniae
• The peak serum concentrations achieved with the standard dosing regimen of the drug (50 mg twice daily) range from 0.6 to 0.9 μg/ml while those attained in the urine and in the epithelial lining fluid are severalfold lower