Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections
Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections
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DOI：
10.1128/aac.02497-17
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发表时间：
2018-05-01
影响因子：
4.9
通讯作者：
Clancy, Cornelius J.
中科院分区：
文献类型：
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作者：
Shields, Ryan K.;Nguyen, M. Hong;Clancy, Cornelius J.
在我中心，头孢他啶-阿维巴坦用于治疗77例碳青霉烯类耐药肠杆菌科（CRE）感染患者。30天和90天生存率分别为81%和69%，这些比率高于感染开始时SAPS II和SOFA评分预测的比率。55%的患者取得了临床成功，但感染部位不同。肺炎的成功率最低（36%），菌血症（75%）和尿路感染（88%）的成功率较高。通过多变量分析，肺炎（P = 0.045）和接受肾脏替代治疗（RRT）（P = 0.046）与临床失败相关。32%的患者发生微生物学失败，感染KPC-3产生CRE的患者比感染KPC-2产生CRE的患者更常见（P = 0.002）。肺炎是微生物学失败的独立预测因子（P = 0.007）。10%的患者出现头孢他啶-阿维巴坦耐药，包括14%的肺炎克雷伯菌感染患者和32%的微生物学失败患者。RRT是耐药发生的独立预测因子（P = 0.009）。抗性仅在K.携带变体KPC-3酶的肺炎细菌。在全基因组序列的系统发育分析，耐药菌株从87.5%（7/8）的患者聚集在一个先前定义的序列类型258（ST 258）进化枝II亚系;耐药菌株从一个病人独立于其他ST 258进化枝II分离株聚类。总之，我们的报告为头孢他啶-阿维巴坦在CRE感染类型中的效用和局限性提供了新的见解。当务之急是确定头孢他啶-阿维巴坦给药和治疗方案，以改善肺炎患者和接受RRT患者的不良结局。
Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant Enterobacteriaceae (CRE) infections at our center. Thirty-and 90-day survival rates were 81% and 69%, respectively; these rates were higher than those predicted by SAPS II and SOFA scores at the onset of infection. Clinical success was achieved for 55% of patients but differed by the site of infection. Success rates were lowest for pneumonia (36%) and higher for bacteremia (75%) and urinary tract infections (88%). By multivariate analysis, pneumonia (P = 0.045) and receipt of renal replacement therapy (RRT) (P = 0.046) were associated with clinical failure. Microbiologic failures occurred in 32% of patients and occurred more commonly among patients infected with KPC-3-producing CRE than among those infected with KPC-2-producing CRE (P = 0.002). Pneumonia was an independent predictor of microbiologic failure (P = 0.007). Ceftazidime-avibactam resistance emerged in 10% of patients, including 14% of those infected with Klebsiella pneumoniae and 32% of those with microbiologic failure. RRT was an independent predictor of the development of resistance (P = 0.009). Resistance was identified exclusively among K. pneumoniae bacteria harboring variant KPC-3 enzymes. Upon phylogenetic analysis of whole-genome sequences, resistant isolates from 87.5% (7/8) of patients clustered within a previously defined sequence type 258 (ST258) clade II sublineage; resistant isolates from one patient clustered independently from other ST258 clade II isolates. In conclusion, our report offers new insights into the utility and limitations of ceftazidime-avibactam across CRE infection types. Immediate priorities are to identify ceftazidime-avibactam dosing and therapeutic regimens that improve on the poor outcomes among patients with pneumonia and those receiving RRT.