Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland.
Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston.
Clin Infect Dis. 2018 Nov 28;67(12):1803-1814. doi: 10.1093/cid/ciy378.
Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic.
The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories.
Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0.
Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.
对所有一线抗生素的耐药性需要使用效果较差或毒性较大的“储备”药物。具有这种难以治疗的耐药性（DTR）的革兰氏阴性菌血流感染（GNBSI）的死亡率可能高于允许至少有一种有效的一线抗生素的表型。
分析了 Premier 数据库中患有特定 GNBSI 的住院患者。DTR 定义为所有β-内酰胺类药物（包括碳青霉烯类和氟喹诺酮类）体外中介/耐药。使用疾病预防控制中心（CDC）的定义，比较 DTR 与耐碳青霉烯类、耐扩展谱头孢菌素类和耐氟喹诺酮类的感染的发生率和氨基糖苷类耐药性。确定 DTR 的预测因素。检查 DTR、CDC 定义的至少有一种一线药物敏感的表型和活性类别逐渐丧失的调整后的相对风险（aRR）与死亡率的关系。
在 2009 年至 2013 年期间，92 家（53.2%）医院的 45011 例 GNBSI 中，有 471 例（1%）表现出 DTR，范围从大肠埃希菌的 0.04%到鲍曼不动杆菌的 18.4%。在 DTR 患者中，79%接受了肠外氨基糖苷类药物、替加环素或多粘菌素 B/多粘菌素 E；33%的患者对所有氨基糖苷类药物均耐药。DTR 的预测因素包括城市医疗保健和更高的基线疾病严重程度。DTR 与耐碳青霉烯类（1.2；95%置信区间，1.0-1.4；P =.02）、耐扩展谱头孢菌素类（1.2；1.1-1.4；P =.001）或耐氟喹诺酮类（1.2；1.0-1.4；P =.008）感染相比，DTR 的粗死亡率更高。每降低一级一线药物的活性，死亡率 aRR 增加 20%，从 3-5 增加到 1-2 再增加到 0。
对一线抗生素的不敏感性与 GNBSI 患者的生存率降低有关。DTR 是一种简单的床边预后指标，可预测治疗性核心耐药性。
