Division of Pulmonary and Critical Care, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah.
University of Utah, Salt Lake City.
JAMA Intern Med. 2020 Apr 1;180(4):552-560. doi: 10.1001/jamainternmed.2019.7495.
Use of empirical broad-spectrum antibiotics for pneumonia has increased owing to concern for resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The association of empirical anti-MRSA therapy with outcomes among patients with pneumonia is unknown, even for high-risk patients.
To compare 30-day mortality among patients hospitalized for pneumonia receiving empirical anti-MRSA therapy vs standard empirical antibiotic regimens.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective multicenter cohort study was conducted of all hospitalizations in which patients received either anti-MRSA or standard therapy for community-onset pneumonia in the Veterans Health Administration health care system from January 1, 2008, to December 31, 2013. Subgroups of patients analyzed were those with initial intensive care unit admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Primary analysis was an inverse probability of treatment-weighted propensity score analysis using generalized estimating equation regression; secondary analyses included an instrumental variable analysis. Statistical analysis was conducted from June 14 to November 20, 2019.
Empirical anti-MRSA therapy plus standard pneumonia therapy vs standard therapy alone within the first day of hospitalization.
Risk of 30-day all-cause mortality after adjustment for patient comorbidities, vital signs, and laboratory results. Secondary outcomes included the development of kidney injury and secondary infections with Clostridioides difficile, vancomycin-resistant Enterococcus species, or gram-negative bacilli.
Among 88 605 hospitalized patients (86 851 men; median age, 70 years [interquartile range, 62-81 years]), empirical anti-MRSA therapy was administered to 33 632 (38%); 8929 patients (10%) died within 30 days. Compared with standard therapy alone, in weighted propensity score analysis, empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio [aRR], 1.4 [95% CI, 1.3-1.5]), kidney injury (aRR, 1.4 [95% CI, 1.3-1.5]), and secondary C difficile infections (aRR, 1.6 [95% CI, 1.3-1.9]), vancomycin-resistant Enterococcus spp infections (aRR, 1.6 [95% CI, 1.0-2.3]), and secondary gram-negative rod infections (aRR, 1.5 [95% CI, 1.2-1.8]). Similar associations between anti-MRSA therapy use and 30-day mortality were found by instrumental variable analysis (aRR, 1.6 [95% CI, 1.4-1.9]) and among patients admitted to the intensive care unit (aRR, 1.3 [95% CI, 1.2-1.5]), those with a high risk for MRSA (aRR, 1.2 [95% CI, 1.1-1.4]), and those with MRSA detected on surveillance testing (aRR, 1.6 [95% CI, 1.3-1.9]). No significant favorable association was found between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1 [95% CI, 0.8-1.4]).
This study suggests that empirical anti-MRSA therapy was not associated with reduced mortality for any group of patients hospitalized for pneumonia. These results contribute to a growing body of evidence that questions the value of empirical use of anti-MRSA therapy using existing risk approaches.
重要性:由于对包括耐甲氧西林金黄色葡萄球菌(MRSA)在内的耐药菌的担忧,经验性使用广谱抗生素治疗肺炎的情况有所增加。抗 MRSA 经验性治疗与肺炎患者结局之间的关联尚不清楚,即使是高危患者也是如此。
目的:比较接受抗 MRSA 经验性治疗与标准经验性抗生素治疗的因社区获得性肺炎住院患者的 30 天死亡率。
设计、地点和参与者:这是一项回顾性多中心队列研究,纳入了 2008 年 1 月 1 日至 2013 年 12 月 31 日期间,退伍军人健康管理系统中因社区获得性肺炎接受抗 MRSA 或标准治疗的所有住院患者。分析的亚组患者包括最初入住重症监护病房、MRSA 危险因素、MRSA 监测检测阳性和 MRSA 入院培养阳性的患者。主要分析采用广义估计方程回归的逆概率治疗加权倾向评分分析;次要分析包括工具变量分析。统计分析于 2019 年 6 月 14 日至 11 月 20 日进行。
暴露:入院第 1 天内接受抗 MRSA 经验性治疗加标准肺炎治疗与仅接受标准治疗。
主要结局和测量指标:调整患者合并症、生命体征和实验室结果后 30 天全因死亡率的风险。次要结局包括肾损伤和艰难梭菌、万古霉素耐药肠球菌属或革兰阴性杆菌的继发性感染。
结果:在 88605 例住院患者(86851 例男性;中位年龄,70 岁[四分位距,62-81 岁])中,33632 例(38%)接受了抗 MRSA 经验性治疗,8929 例(10%)患者在 30 天内死亡。与单独接受标准治疗相比,在加权倾向评分分析中,抗 MRSA 经验性治疗加标准治疗与调整后死亡风险增加显著相关(调整风险比[aRR],1.4[95%CI,1.3-1.5]),肾损伤(aRR,1.4[95%CI,1.3-1.5])和继发性艰难梭菌感染(aRR,1.6[95%CI,1.3-1.9])、万古霉素耐药肠球菌属感染(aRR,1.6[95%CI,1.0-2.3])和继发性革兰阴性杆菌感染(aRR,1.5[95%CI,1.2-1.8])。通过工具变量分析(aRR,1.6[95%CI,1.4-1.9])和重症监护病房收治患者(aRR,1.3[95%CI,1.2-1.5])、MRSA 高危患者(aRR,1.2[95%CI,1.1-1.4])和监测检测到 MRSA 的患者(aRR,1.6[95%CI,1.3-1.9])也发现了抗 MRSA 治疗使用与 30 天死亡率之间的类似关联。在培养物中检测到 MRSA 的患者中,抗 MRSA 经验性治疗与死亡之间没有显著的有利关联(aRR,1.1[95%CI,0.8-1.4])。
结论和相关性:这项研究表明,抗 MRSA 经验性治疗与任何因肺炎住院的患者的死亡率降低均无关。这些结果为越来越多的质疑使用现有风险方法进行抗 MRSA 经验性使用价值的证据提供了补充。