Prevalence of Antibiotic-Resistant Pathogens in Culture-Proven Sepsis and Outcomes Associated With Inadequate and Broad-Spectrum Empiric Antibiotic Use
Prevalence of Antibiotic-Resistant Pathogens in Culture-Proven Sepsis and Outcomes Associated With Inadequate and Broad-Spectrum Empiric Antibiotic Use
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DOI：
10.1001/jamanetworkopen.2020.2899
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发表时间：
2020-04-16
影响因子：
13.8
通讯作者：
Klompas, Michael
中科院分区：
文献类型：
--
作者：
Rhee, Chanu;Kadri, Sameer S.;Klompas, Michael
重要性建议所有疑似脓毒症的患者使用广谱抗生素，以最大限度地减少治疗不足的风险。然而，关于所有社区起病脓毒症患者中抗生素耐药病原体的净流行率或与不必要的广泛经验治疗相关的结果知之甚少。目的阐明培养阳性社区起病脓毒症患者中抗生素耐药病原体的流行病学以及与治疗不足和过度治疗相关的结果。设计、背景和参与者这项队列研究包括2009年1月至2015年12月在美国104家医院住院的17 430名脓毒症患者，入院后2天内临床培养阳性。数据分析发生在2018年1月至2019年12月，发现经验性抗生素治疗不足(即，=1种在治疗第一天或第二天给予所有抗生素不敏感的病原体)和不必要的广泛经验性治疗(例如，对耐甲氧西林金黄色葡萄球菌[MRSA]；对万古霉素耐药肠球菌[VRE]；耐头孢曲松革兰氏阴性[CTX-RO]细菌，包括铜绿假单胞菌；结果17 430例培养阳性社区败血症患者(年龄中位数69[四分位数范围]69[57-81]岁；女性9737例[55.9%])，2865例(16.4%)在医院死亡。最常见的培养阳性部位是尿液(9077例(52.1%))、血液(6968例(40.0%))和呼吸道(2912例(16.7%))。最常见的病原菌是大肠埃希菌5873株(33.7%)、S金黄色葡萄球菌3706株(21.3%)、链球菌2361株(13.5%)。在15183例可计算出所有抗生素-病原体药敏组合的病例中，大多数(12398例，81.6%)应用了足够的经验性抗生素。17430例患者中有11683例耐药菌(67.0%，主要是万古霉素和β-内酰胺类抗生素)，但耐药菌并不常见(MRSA，2045例(11.7%)；CTX-RO，2278例(13.1%)；VRE，360例(2.1%)；ESBLS，133例(0.8%))。至少1种耐药革兰氏阳性菌(即MRSA或VRE)的净感染率为13.6%(2376例)，至少1种耐药的革兰氏阴性菌(即CTX-RO、ESBL或CRE)的净患病率为13.2%(2297例)。经过详细的风险调整(不足的经验性抗生素：优势比，1.19；95%CI，1.03-1.37；P=0.02；不必要的宽泛经验性抗生素：优势比，1.22；95%的CI，1.06-1.40；P=.007)，不足和不必要的广泛经验性抗生素都与更高的死亡率相关。结论和相关性在本研究中，大多数社区起病的脓毒症患者没有耐药病原菌，但广谱抗生素经常被使用。经验抗生素的不足和不必要的广泛都与较高的死亡率有关。这些发现强调了需要更好的测试来快速识别耐药病原体的患者，并需要更明智地使用广谱抗生素进行经验性脓毒症治疗。
Importance Broad-spectrum antibiotics are recommended for all patients with suspected sepsis to minimize the risk of undertreatment. However, little is known regarding the net prevalence of antibiotic-resistant pathogens across all patients with community-onset sepsis or the outcomes associated with unnecessarily broad empiric treatment.Objective To elucidate the epidemiology of antibiotic-resistant pathogens and the outcomes associated with both undertreatment and overtreatment in patients with culture-positive community-onset sepsis.Design, Setting, and Participants This cohort study included 17 430 adults admitted to 104 US hospitals between January 2009 and December 2015 with sepsis and positive clinical cultures within 2 days of admission. Data analysis took place from January 2018 to December 2019.Exposures Inadequate empiric antibiotic therapy (ie, >= 1 pathogen nonsusceptible to all antibiotics administered on the first or second day of treatment) and unnecessarily broad empiric therapy (ie, active against methicillin-resistant Staphylococcus aureus [MRSA]; vancomycin-resistant Enterococcus [VRE]; ceftriaxone-resistant gram-negative [CTX-RO] organisms, including Pseudomonas aeruginosa; or extended-spectrum beta-lactamase [ESBL] gram-negative organisms when none of these were isolated).Main Outcomes and Measures Prevalence and empiric treatment rates for antibiotic-resistant organisms and associations of inadequate and unnecessarily broad empiric therapy with in-hospital mortality were assessed, adjusting for baseline characteristics and severity of illness.Results Of 17 430 patients with culture-positive community-onset sepsis (median [interquartile range] age, 69 [57-81] years; 9737 [55.9%] women), 2865 (16.4%) died in the hospital. The most common culture-positive sites were urine (9077 [52.1%]), blood (6968 [40.0%]), and the respiratory tract (2912 [16.7%]). The most common pathogens were Escherichia coli (5873 [33.7%]), S aureus (3706 [21.3%]), and Streptococcus species (2361 [13.5%]). Among 15 183 cases in which all antibiotic-pathogen susceptibility combinations could be calculated, most (12 398 [81.6%]) received adequate empiric antibiotics. Empiric therapy targeted resistant organisms in 11 683 of 17 430 cases (67.0%; primarily vancomycin and anti-Pseudomonal beta-lactams), but resistant organisms were uncommon (MRSA, 2045 [11.7%]; CTX-RO, 2278 [13.1%]; VRE, 360 [2.1%]; ESBLs, 133 [0.8%]). The net prevalence for at least 1 resistant gram-positive organism (ie, MRSA or VRE) was 13.6% (2376 patients), and for at least 1 resistant gram-negative organism (ie, CTX-RO, ESBL, or CRE), it was 13.2% (2297 patients). Both inadequate and unnecessarily broad empiric antibiotics were associated with higher mortality after detailed risk adjustment (inadequate empiric antibiotics: odds ratio, 1.19; 95% CI, 1.03-1.37; P = .02; unnecessarily broad empiric antibiotics: odds ratio, 1.22; 95% CI, 1.06-1.40; P = .007).Conclusions and Relevance In this study, most patients with community-onset sepsis did not have resistant pathogens, yet broad-spectrum antibiotics were frequently administered. Both inadequate and unnecessarily broad empiric antibiotics were associated with higher mortality. These findings underscore the need for better tests to rapidly identify patients with resistant pathogens and for more judicious use of broad-spectrum antibiotics for empiric sepsis treatment.