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经验性第三代头孢菌素治疗成人社区获得性肠杆菌科菌血症:CLSI 折点修订的影响。

Empirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia: Impact of revised CLSI breakpoints.

机构信息

Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.

出版信息

Int J Antimicrob Agents. 2016 Apr;47(4):297-303. doi: 10.1016/j.ijantimicag.2016.01.010. Epub 2016 Feb 23.

Abstract

Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n=409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR)=19.96; P<0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR=13.91; P<0.001); bacteraemia because of pneumonia (OR=5.45; P=0.007); de-escalation after empirical therapy (OR=0.28; P=0.03); and isolates with a CTX MIC≤1mg/L (OR=0.17; P=0.02). Of note, isolates with a CTX MIC≤8mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ=1.00; P=0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC≤1mg/L.

摘要

第三代头孢菌素(3GCs)[头孢曲松(CRO)和头孢噻肟(CTX)]对肠杆菌科具有显著的活性,常用于治疗社区获得性菌血症。然而,支持临床和实验室标准协会(CLSI)更新解释标准的临床证据有限。本研究招募了接受经验性 CRO 或 CTX 治疗的社区获得性单一肠杆菌科菌血症的成年患者。从病历中收集临床信息,并使用肉汤微量稀释法测定 CTX MIC。根据明确抗生素的类型,将符合条件的患者(n=409)分为降级(260;63.6%)、未换药(115;28.1%)和升级(34;8.3%)组。多变量回归显示 28 天死亡率的 5 个独立预测因素:根据 McCabe 分类的致命合并症[比值比(OR)=19.96;P<0.001];菌血症发病时高 Pitt 菌血症评分(≥4)(OR=13.91;P<0.001);肺炎引起的菌血症(OR=5.45;P=0.007);经验性治疗后降级(OR=0.28;P=0.03);以及 CTX MIC≤1mg/L 的分离株(OR=0.17;P=0.02)。值得注意的是,CTX MIC≤8mg/L 的分离株(以前的 CLSI 折点表示敏感)与死亡率无关。此外,临床失败和 28 天死亡率有随着 CTX MIC 增加而增加的趋势(γ=1.00;P=0.01)。综上所述,本研究关注接受经验性 3GC 治疗的社区获得性肠杆菌科菌血症患者,提供了具有临床重要意义的证据,验证了将 CTX 敏感性折点降低至 MIC≤1mg/L 的建议。

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