Department of Pharmacy Practice, St. Louis College of Pharmacy, St. Louis, Missouri.
John Cochran Division, VA St. Louis Health Care System, St. Louis, Missouri.
Pharmacotherapy. 2019 Mar;39(3):261-270. doi: 10.1002/phar.2201. Epub 2019 Jan 7.
Minimizing the duration of broad-spectrum antimicrobial exposure in the critically ill is a commonly used strategy aimed at preventing resistance. Our objective was to correlate the duration of exposure to antipseudomonal β-lactam antibiotics with the development of new resistance in critically ill patients.
Single-center, retrospective cohort study.
A large, academic, tertiary care hospital.
A total of 7118 adults with a discharge diagnosis of severe sepsis or septic shock who received at least one dose of cefepime, meropenem, or piperacillin-tazobactam during their hospitalization between 2010 and 2015.
Cohort entry was defined as the first day of any antipseudomonal β-lactam initiation, and exposure was defined as the cumulative days of any antipseudomonal β-lactam exposure during the 60-day follow-up period. The primary outcome was development of new resistance to any antipseudomonal β-lactam > 3 days after cohort entry. New resistance was defined as detection of resistance to any antipseudomonal β-lactam not identified within 180 days before cohort entry. Patients without an outcome (i.e., did not develop new resistance) or who died by day 60 were censored. Cox proportional hazards models were performed to assess the risk of development of new resistance to any antipseudomonal β-lactam with each additional day of exposure. Analyses of each individual antipseudomonal β-lactam were evaluated as secondary outcomes. Each additional day of exposure to any antipseudomonal β-lactam resulted in an adjusted hazard ratio (aHR) of 1.04 (95% confidence interval [CI] 1.04-1.05) for new resistance development. The risk of developing new resistance to cefepime, meropenem, and piperacillin-tazobactam for each additional day of exposure resulted in an aHR of 1.08 (95% CI 1.07-1.09), 1.02 (95% CI 1.01-1.03), and 1.08 (95% CI 1.06-1.09), respectively.
Among critically ill patients who receive antipseudomonal β-lactam antibiotics, each additional day of exposure to cefepime, meropenem, and piperacillin-tazobactam is associated with an increased risk of new resistance development.
在危重病患者中，尽量减少广谱抗菌药物的暴露时间是预防耐药性的常用策略。我们的目的是将抗假单胞菌β-内酰胺类抗生素的暴露时间与危重病患者新耐药的发展相关联。
单中心回顾性队列研究。
一家大型学术性三级护理医院。
2010 年至 2015 年期间，共有 7118 名因严重败血症或感染性休克出院的成年人，他们在住院期间至少接受了一次头孢吡肟、美罗培南或哌拉西林他唑巴坦治疗。
队列进入定义为开始使用任何抗假单胞菌β-内酰胺类药物的第一天，暴露定义为在 60 天随访期间任何抗假单胞菌β-内酰胺类药物的累积暴露天数。主要结局是在队列进入后 3 天以上出现对任何抗假单胞菌β-内酰胺类药物的新耐药性。新耐药性定义为在队列进入前 180 天内未发现的任何抗假单胞菌β-内酰胺类药物的耐药性检测。没有结局（即没有出现新的耐药性）或在第 60 天死亡的患者被删失。使用 Cox 比例风险模型评估每增加一天暴露对任何抗假单胞菌β-内酰胺类药物新耐药性发展的风险。对每种单独的抗假单胞菌β-内酰胺类药物的分析作为次要结局进行评估。任何抗假单胞菌β-内酰胺类药物的暴露时间每增加一天，新耐药性发展的调整后危险比（aHR）为 1.04（95%置信区间[CI]1.04-1.05）。对于每种额外的抗假单胞菌β-内酰胺类药物暴露，新耐药性发展的 aHR 分别为 1.08（95%CI1.07-1.09）、1.02（95%CI1.01-1.03）和 1.08（95%CI1.06-1.09）。
在接受抗假单胞菌β-内酰胺类抗生素治疗的危重病患者中，头孢吡肟、美罗培南和哌拉西林他唑巴坦的暴露时间每增加一天，新耐药性发展的风险就会增加。
