MIC profiling of ceftazidime/avibactam against two carbapenemase-producing Klebsiella pneumoniae isolates.
MIC profiling of ceftazidime/avibactam against two carbapenemase-producing Klebsiella pneumoniae isolates.
复制标题
DOI：
10.1016/j.jgar.2020.10.014
复制
发表时间：
2020-12
影响因子：
4.6
通讯作者：
Tam VH
中科院分区：
文献类型：
--
作者：
Zidaru A;Eales BM;Wang W;Merlau PR;Lasco TM;Sofjan AK;Tam VH
将改良药敏试验方法的结果与头孢他啶-阿维巴坦（CAZ/AVI）治疗的结局相关联。两个血流K。从2名无关患者中回收了来自腹部来源的肺炎分离株（CAZ/AVI易感）。两例患者均接受CAZ/AVI治疗，但结局不一致：KP 118（24小时内根除）和KP 286（持续菌血症超过30天）。通过Carba NP试验证实了两种分离株中的碳青霉烯酶产生。采用递增的阿维巴坦浓度（0 - 16 mg/L）测定CAZ最小抑菌浓度（MIC）。浓度-反应的特征在于S形抑制最大效应模型。最佳拟合参数值用于预测标准给药（每8小时2.5 g）后腹膜液中预期CAZ/AVI暴露相关的%T>MICi。这些CAZ/AVI暴露在中空纤维感染模型（HISTORY）中进行模拟，细菌反应与观察到的临床结果相关。在两种细菌分离株中，CAZ MIC的AVI依赖性降低得到了很好的表征（r2 > 0.98）。在HPLOS中，观察到持续抑制KP 118（T>MICi = 100%）超过5天，但KP 286（T>MICi < 100%）未观察到。这些观察结果与患者的临床病程一致。不一致的患者结局可能由CAZ/AVI的MIC谱解释。该方法在预测CAZ/AVI治疗的阳性临床结局方面似乎比传统的药敏试验更稳健，并且该方法的临床实用性应进一步研究。
To correlate results of a modified susceptibility testing method to outcomes of ceftazidime-avibactam (CAZ/AVI) therapy. Two bloodstream K. pneumoniae isolates (CAZ/AVI susceptible) from an abdominal source were recovered from 2 unrelated patients. Both patients were treated with CAZ/AVI but had discordant outcomes: KP118 (eradication within 24h) and KP286 (persistent bacteremia for over 30 days). Carbapenemase production in the two isolates was confirmed via Carba NP test. CAZ minimum inhibitory concentration (MIC) was determined with escalating avibactam concentration (0 – 16 mg/L). The concentration-response was characterized by the sigmoid inhibitory maximum effect model. The best-fit parameter values were used to predict %T>MICi associated with CAZ/AVI exposures expected in peritoneal fluid after standard dosing (2.5g every 8h). These CAZ/AVI exposures were simulated in the hollow-fiber infection model (HFIM), and the bacterial responses were correlated to observed clinical outcomes. The AVI-dependent reduction in CAZ MIC was well characterized in both bacterial isolates (r2 > 0.98). In HFIM, sustained suppression of KP118 (T>MICi = 100%) was observed over 5 days, but not with KP286 (T>MICi < 100%). These observations are consistent with the clinical courses of the patients. The discordant patient outcomes could be potentially explained by MIC profiling of CAZ/AVI. This method appears to be more robust than conventional susceptibility testing in predicting positive clinical outcome of CAZ/AVI therapy, and the clinical utility of this approach should be further investigated.
影响因子：
4.9
作者：
Chauzy, Alexia;Lamarche, Isabelle;Marchand, Sandrine
通讯作者：
Marchand, Sandrine
影响因子：
5.2
作者：
Tam, Vincent H.;Abodakpi, Henrietta;Sofjan, Amelia K.
通讯作者：
Sofjan, Amelia K.