Optimal early vancomycin target exposure remains controversial. To clarify the therapeutic exposure range, we investigated the association between vancomycin exposure and treatment outcomes or nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. This retrospective study reviewed clinical data obtained from 131 patients with MRSA infections between January 2017 and September 2019. Clinical outcomes included treatment failure, 30-day mortality, microbiological failure, and acute kidney injury. We measured serum vancomycin levels after the first dose to 48 h and estimated vancomycin exposure using the Bayesian theorem. The minimum inhibitory concentration (MIC) of antimicrobial agents was determined using the broth microdilution method. Classification and Regression Tree analyses identified day 1 and 2 exposure thresholds associated with an increased risk of failure and nephrotoxicity. Treatment failure (27.9% vs. 33.3%) and 30-day mortality (26.6% vs. 31.74%) were numerically but not significantly reduced in patients with the area under the curve (AUC)_24–48h/MIC_BMD ≥ 698. Patients with AUC_ss/MIC_BMD ≥ 679 exhibited a significantly increased risk of acute kidney injury (27.9% vs. 10.9%, p = 0.041). These findings indicate that AUC_ss/MIC_BMD ratios > 600 may cause nephrotoxicity. AUC/MIC_BMD at days 1 and 2 do not appear to be significantly associated with particular clinical outcomes, but further studies are needed.

中文翻译：

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早期监测更好吗？万古霉素早期暴露对耐甲氧西林金黄色葡萄球菌感染患者的治疗效果和肾毒性的影响

最佳万古霉素靶标早期暴露仍存在争议。为了阐明治疗暴露范围，我们研究了万古霉素暴露与耐甲氧西林金黄色葡萄球菌患者的治疗结果或肾毒性之间的关联（MRSA）感染。这项回顾性研究回顾了2017年1月至2019年9月期间从131例MRSA感染患者中获得的临床数据。临床结果包括治疗失败，30天死亡率，微生物学失败和急性肾损伤。我们测量了首次给药后48小时的血清万古霉素水平，并使用贝叶斯定理估算了万古霉素的暴露量。使用肉汤微稀释法确定抗菌剂的最低抑菌浓度（MIC）。分类和回归树分析确定了第1天和第2天的暴露阈值与失败和肾毒性风险增加相关。在曲线下面积（AUC）的患者中，治疗失败（27.9％vs. 33.3％）和30天死亡率（26.6％vs. 31.74％）有所数字，但没有显着降低_24-48小时/ MIC _BMD ≥698.患者AUC _SS / MIC _BMD ≥679表现出显著增加急性肾损伤（27.9％对10.9％，的风险p = 0.041）。这些发现表明AUC _ss / MIC _BMD比> 600可能会引起肾毒性。第1天和第2天的AUC / MIC _BMD似乎与特定的临床结果没有显着相关，但需要进一步的研究。