使用头孢妥珠治疗耐碳青霉烯类鲍曼不动杆菌感染的患者对头孢妥珠产生异抗性的频率。

IF 3.7 Q2 INFECTIOUS DISEASES JAC-Antimicrobial Resistance Pub Date : 2024-09-09 eCollection Date: 2024-10-01 DOI:10.1093/jacamr/dlae146
Ryan K Shields, Ava J Dorazio, Giusy Tiseo, Kevin M Squires, Alessandro Leonildi, Cesira Giordano, Ellen G Kline, Simona Barnini, Alina Iovleva, Marissa P Griffith, Daria Van Tyne, Yohei Doi, Marco Falcone
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引用次数: 0

摘要

背景:头孢克洛对耐碳青霉烯类鲍曼不动杆菌(CRAb)具有很强的体外活性,但这种活性并不能持续改善患者的治疗效果。有人提出头孢哌酮异质性耐药性或耐药亚群的存在是一种可能的解释。本研究的目的是探讨异抗性与 CRAb 感染患者预后之间的关联:方法:从美国和意大利的 27 名连续患者中收集基线 CRAb 分离物。一式三份的肉汤微量稀释法检测头孢菌素敏感性。一式两份的群体分析图谱确定了异抗性。通过比较基因组分析评估了耐药机制和菌株亲缘关系:结果:总体而言,59%的感染 CRAb 分离物被鉴定为对头孢球蛋白产生异抗;来自意大利的分离物(79%)的异抗率高于美国(38%)。夏尔森合并症和 SOFA 评分的中位数分别为 4 分和 5 分;44% 的患者患有肺炎,这是最常见的感染类型。28 天临床成功率和存活率分别为 30% 和 73%。肉汤微稀释法显示,头孢羟氨苄 MIC 值≥1 毫克/升的失败率高于 MIC 值≤0.5 毫克/升的失败率(81% 对 55%)。与易感 CRAb 相比,耐头孢球蛋白患者的临床失败率更高(81% 对 55%)。全基因组测序在 6 个分离株中发现了 TonB 依赖性受体基因 piuA 中的过早终止密码子,所有这些分离株都具有异抗性:这项试点研究支持这样的假设:头孢哌酮治疗失败可能与较高的 MICs 和/或存在异抗性有关。需要进一步研究来证实这些发现。
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Frequency of cefiderocol heteroresistance among patients treated with cefiderocol for carbapenem-resistant Acinetobacter baumannii infections.

Background: Cefiderocol exhibits potent in vitro activity against carbapenem-resistant Acinetobacter baumannii (CRAb), but this activity has not consistently translated to improved outcomes among patients. Cefiderocol heteroresistance, or the presence of a resistant subpopulation, has been proposed as one possible explanation. The objective of this study was to explore associations between heteroresistance and outcomes of patients with CRAb infections.

Methods: Baseline CRAb isolates were collected from 27 consecutive patients in the USA and Italy. Cefiderocol susceptibility was tested by broth microdilutions in triplicate. Heteroresistance was defined by population analysis profiling in duplicate. Resistance mechanisms and strain relatedness were evaluated through comparative genomic analysis.

Results: Overall, 59% of infecting CRAb isolates were identified as cefiderocol-heteroresistant; rates were higher among isolates from Italy (79%) than the USA (38%). The median Charlson Comorbidity and SOFA scores were 4 and 5, respectively; 44% of patients had pneumonia, which was the most common infection type. Rates of 28-day clinical success and survival were 30% and 73%, respectively. By broth microdilution, cefiderocol MICs ≥1 mg/L were associated with higher failure rates than MICs ≤0.5 mg/L (81% versus 55%). Rates of clinical failure were numerically higher among patients infected by cefiderocol-heteroresistant compared with susceptible CRAb (81% versus 55%). Whole-genome sequencing identified a premature stop codon in the TonB-dependent receptor gene piuA in six isolates, all of which were heteroresistant.

Conclusions: This pilot study supports the hypothesis that cefiderocol treatment failure may be associated with higher MICs and/or the presence of heteroresistance. Further studies are needed to confirm these findings.

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