多重耐药革兰阴性菌感染治疗.pptxVIP

多重耐药革兰阴性菌感染与治疗细菌感染性疾病治疗经验性治疗：根据病史、症状、体征及实验室检查，得出初步诊断，评估可能病原体和耐药性后，病情评估后使用抗菌药物。目标治疗：感染部位、病原菌及药敏已明确，有针对性的使用抗菌药物。Antibiotic treatment Appropriate initial antibiotic treatmentAvoidunnecessaryantibioticsA balancing actImproving the Probability of Positive OutcomesAppropriate therapyMatches antibiotic sensitivities of the organism to the antibiotic usedADEQUATE therapyChoose an appropriate initial antibiotic therapyUse optimal dosing (PD profiling)Select correct route of administration to ensure antibiotic penetration at site of infectionUse combination therapy, if necessaryATS/IDSA Guidelines. Am J Respir Crit Care Med. 2005;171:388-416.4030Inappropriate treatment (%)20100Pseudomonas aeruginosaAcinetobacterspp.S. aureusOtherKlebsiella pneumoniaeDoes Inappropriate Therapy Result From Antibiotic Resistance?Inappropriate therapy is more likely if antibiotic resistance is presentAntibiotic-resistant organisms are more commonly associated with inappropriate therapyAdapted from Kollef MH. Clin Infect Dis. 2000;31(suppl 4):S131–S138.感染部位浓度药动学（ADME）结果药 物病原菌体外药效MIC临床疗效细菌清除耐药性PK/PD药效学优化抗菌治疗的重要理论依据是药动学/药效学(PK/PD)研究的成果以血浓度代表?-内酰胺类: 优化药物暴露时间PK/PD靶值：疗效最大化所需要的 %TMIC 头孢菌素类60%–70% 青霉素类50% 碳青霉烯类 40% 40～50％→临床疗效：85％以上60～70％ →最佳细菌学疗效Drusano GL. Clin Infect Dis. 2003;36(suppl 1):S42-S50.肠杆菌科细菌 临床关注的主要?-内酰胺酶超广谱?-内酰胺酶(ESBLs)高产头孢菌素酶(AmpC酶)极少数菌株产碳青霉烯酶 (碳青霉烯酶KPC)MDRXDR or PDR产ESBLs菌株血行感染死亡率显著增加（Meta分析）产ESBLs菌株与不产ESBLs菌株血行感染死亡率比较的Meta分析包括16个研究产ESBLs菌株菌血症死亡率显著增加(pooled RR 1.85, 95% CI 1.39–2.47, P 0.001） Mortality and delay in effective therapy associated with extended-spectrum b-lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. Journal of Antimicrobial Chemotherapy (2007) 60, 913–920产ESBLs菌株亚胺培南MIC分布美罗培南和亚胺培南的血浆浓度（1g）（常规剂量：0.5 Q6H；最少剂量： 0.5 Q8H）TMICs 40%以上MIC90亚胺培南美罗培南Dreetz M et al. Antimicrob Agents Chemother 1996;40:105-109.抗菌药物对产ESBLs菌抗菌活性8％ 218％ 430％ 817% 1615% 322% 6410% 耐药3.0 Q8h3.0 Q12h头孢哌酮/舒巴坦(2:1) PK/PD研究MIC：32mg/LMIC：64mg/LMIC：16mg/L 经验性抗