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哌拉西林-他唑巴坦与其他抗菌药物治疗产AmpCβ-内酰胺酶肠杆菌科细菌所致血流感染的比较

Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC β-Lactamase-Producing Enterobacteriaceae.

作者信息

Cheng Lucy, Nelson Brian C, Mehta Monica, Seval Nikhil, Park Sarah, Giddins Marla J, Shi Qiuhu, Whittier Susan, Gomez-Simmonds Angela, Uhlemann Anne-Catrin

机构信息

Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.

NewYork-Presbyterian Hospital, New York, New York, USA.

出版信息

Antimicrob Agents Chemother. 2017 May 24;61(6). doi: 10.1128/AAC.00276-17. Print 2017 Jun.

Abstract

induction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics in , often resulting in the need to use carbapenems or cefepime (FEP). The clinical effectiveness of piperacillin-tazobactam (TZP), a weak inducer of AmpC beta-lactamases, is poorly understood. Here, we conducted a case-control study of adult inpatients with bloodstream infections (BSIs) due to , , or species from 2009 to 2015 to assess outcomes following treatment with TZP compared to FEP or meropenem (MEM). We collected clinical data and screened all isolates for the presence of alleles by PCR. Primary study outcomes were 30-day mortality and persistent bacteremia at ≥72 h from the time of treatment initiation. Of 493 patients with bacteremia, 165 patients met the inclusion criteria, of which 88 were treated with TZP and 77 with FEP or MEM. To minimize differences between covariates, we carried out propensity score matching, which yielded 41 matched pairs. Groups only differed by age, with patients in the TZP group significantly older ( = 0.012). There were no significant differences in 30-day mortality, persistent bacteremia, 7-day mortality, or treatment escalation between the two treatment groups, including in the propensity score-matched cohort. PCR amplification and sequencing of C genes revealed the presence of C in isolates with cefoxitin MICs below 16 μg/ml, in particular in spp., and demonstrated that these alleles were highly genetically diverse. Taken together, TZP may be a valuable treatment option for BSIs due to AmpC beta-lactamase-producing , diminishing the need for broader-spectrum agents. Future studies are needed to validate these findings.

摘要

AmpCβ-内酰胺酶的诱导会导致许多β-内酰胺类抗生素产生高水平耐药性,通常需要使用碳青霉烯类或头孢吡肟(FEP)。哌拉西林-他唑巴坦(TZP)作为AmpCβ-内酰胺酶的弱诱导剂,其临床疗效尚不清楚。在此,我们对2009年至2015年因肠杆菌科细菌、铜绿假单胞菌或不动杆菌属菌种导致血流感染(BSIs)的成年住院患者进行了一项病例对照研究,以评估与FEP或美罗培南(MEM)相比,TZP治疗后的结局。我们收集了临床数据,并通过PCR筛选所有分离株中AmpC等位基因的存在情况。主要研究结局为治疗开始后30天死亡率和≥72小时的持续性菌血症。在493例菌血症患者中,165例患者符合纳入标准,其中88例接受TZP治疗,77例接受FEP或MEM治疗。为尽量减少协变量之间的差异,我们进行了倾向评分匹配,得到41对匹配对。两组仅在年龄上存在差异,TZP组患者年龄显著更大(P = 0.012)。两个治疗组之间在30天死亡率、持续性菌血症、7天死亡率或治疗升级方面均无显著差异,包括在倾向评分匹配队列中。对AmpC基因进行PCR扩增和测序显示,在头孢西丁MIC低于16μg/ml的分离株中存在AmpC,特别是在阴沟肠杆菌中,并表明这些等位基因在遗传上高度多样。综上所述,TZP可能是治疗由产AmpCβ-内酰胺酶的肠杆菌科细菌引起的BSIs的一种有价值的治疗选择,从而减少对更广谱药物的需求。需要进一步的研究来验证这些发现。

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