Trinh Trang D, Zasowski Evan J, Claeys Kimberly C, Casapao Anthony M, Compton Matthew, Lagnf Abdalhamid, Kidambi Shravya D, Levine Donald P, Rybak Michael J
Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA, USA.
Infect Dis Ther. 2018 Mar;7(1):161-169. doi: 10.1007/s40121-018-0187-0. Epub 2018 Feb 22.
Vancomycin remains the standard of care for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Treatment failures from heteroresistant vancomycin-intermediate subpopulations (hVISA) are challenging to detect. Minimum inhibitory concentrations (MIC) identified by modified population analysis profile (PAP) is an alternative testing method. The aim of this study was to evaluate the role of PAP MIC on vancomycin failures in two high inoculum infections: MRSA infective endocarditis and pneumonia.
Retrospective, observational study at Detroit Medical Center from 2008 to 2016. Adults ≥ 18 years with ≥ 1 positive MRSA blood culture from IE or pneumonia source and received ≥ 48 h vancomycin were included. The primary outcome was composite failure: MRSA bacteremia ≥ 7 days or 30-day all-cause mortality.
A total of 191 patients were included; 47.6% IE and 52.4% pneumonia. About 19% were hVISA isolates, median vancomycin PAP MIC of 3 (2, 3). More than half (54.5%) experienced composite failure with a larger proportion of PAP MIC ≥ 4 mg/L in this group (25 vs. 15%, p = 0.086). Patients with IE experienced prolonged bacteremia whereas patients with pneumonia experienced higher 30-day mortality. On logistic regression analysis, age [adjusted odds ratio (aOR), 1.026; 95% confidence interval (CI), 1.005-1.047; p = 0.014] and APACHE II score (aOR 1.039; 95% CI, 1.004-1.076; p = 0.029) independently predicted composite failure.
Vancomycin PAP MIC may be a more relevant predictor of patient outcomes in persistent bacteremic MRSA infections (e.g., IE). This susceptibility method is less applicable in other high inoculum infections with shorter bacteremia durations and higher mortality rates (e.g., pneumonia).
万古霉素仍然是侵袭性耐甲氧西林金黄色葡萄球菌（MRSA）感染治疗的标准药物。检测由异质性万古霉素中介亚群（hVISA）导致的治疗失败具有挑战性。通过改良群体分析谱（PAP）确定的最低抑菌浓度（MIC）是一种替代检测方法。本研究的目的是评估PAP MIC在两种高接种量感染（MRSA感染性心内膜炎和肺炎）中万古霉素治疗失败中的作用。
2008年至2016年在底特律医疗中心进行的回顾性观察研究。纳入年龄≥18岁、来自感染性心内膜炎或肺炎源的MRSA血培养≥1次阳性且接受万古霉素治疗≥48小时的成年人。主要结局是复合失败：MRSA菌血症≥7天或30天全因死亡率。
共纳入191例患者；47.6%为感染性心内膜炎，52.4%为肺炎。约19%为hVISA分离株，万古霉素PAP MIC中位数为3（2，3）。超过一半（54.5%）经历了复合失败，该组中PAP MIC≥4mg/L的比例更高（25%对15%，p=0.086）。感染性心内膜炎患者菌血症持续时间延长，而肺炎患者30天死亡率更高。逻辑回归分析显示，年龄[调整优势比（aOR），1.026；95%置信区间（CI），1.005-1.047；p=0.014]和急性生理与慢性健康状况评分系统II（APACHE II）评分（aOR 1.039；95%CI,1.004-1.076；p=0.029）独立预测复合失败。
万古霉素PAP MIC可能是持续性菌血症性MRSA感染（如感染性心内膜炎）患者预后更相关的预测指标。这种药敏方法在菌血症持续时间较短且死亡率较高的其他高接种量感染（如肺炎）中适用性较差。
