The impact of polymyxin B dosage on in-hospital mortality of patients treated with this antibiotic
The impact of polymyxin B dosage on in-hospital mortality of patients treated with this antibiotic
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DOI：
10.1093/jac/dkq285
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发表时间：
2010-10-01
影响因子：
5.2
通讯作者：
Zavascki, Alexandre P.
中科院分区：
文献类型：
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作者：
Elias, Laura S.;Konzen, Daniele;Zavascki, Alexandre P.
为了评估剂量对接受静脉注射多粘菌素B的患者的院内死亡率的影响，从2003年1月至2009年12月进行了一项回顾性队列研究。分析了年龄≥ 18岁、静脉注射多粘菌素B ≥ 72 h的患者。评估临床协变量，并从病历中检索数据。在微生物学证实的感染患者和菌血症患者中进行亚组分析。还评估了肾毒性。对整个队列和亚组进行Logistic回归分析，共纳入276例患者。总住院死亡率为60.5%（167/276）。最终LRM显示严重脓毒症或脓毒性休克[校正比值比（aOR）4.07; 95%置信区间（CI）2.22-7.46]，机械通气的存在（aOR 3.14; 95% CI 1.73-5.71），Charlson共病评分（aOR 1.25; 95% CI 1.09-1.44）和年龄（aOR 1.02; 95%CI 1.01-1.04）与院内死亡率增加独立相关，而多粘菌素B ≥ 200 mg/天与该结局的风险降低相关（aOR 0.43; 95% CI 0.23-0.79）。多粘菌素B ≥ 200 mg/天对两个亚组（微生物记录的感染和菌血症）的住院死亡率的影响更高。多粘菌素B剂量≥ 200 mg/d的患者发生严重肾损害的风险显著升高，多粘菌素B剂量≥ 200 mg/d的患者住院死亡率较低。这些较高剂量的获益超过治疗期间重度肾功能不全的风险。仍需要开展包括药代动力学/药效学分析在内的大型前瞻性研究，以确定多粘菌素B的最佳给药方案。
To assess the impact of dosage on in-hospital mortality of patients receiving intravenous polymyxin B.A retrospective cohort study was performed from January 2003 to December 2009. Patients >= 18 years receiving intravenous polymyxin B for >= 72 h were analysed. Clinical covariates were assessed and data were retrieved from medical records. Subgroup analyses were performed in patients with microbiologically confirmed infections and in patients with bacteraemia. Renal toxicity was also assessed. Logistic regression models (LRMs) were performed for the entire cohort and subgroups.A total of 276 patients were included. The overall in-hospital mortality was 60.5% (167 of 276). The final LRM showed that severe sepsis or septic shock [adjusted odds ratio (aOR) 4.07; 95% confidence interval (CI) 2.22-7.46], presence of mechanical ventilation (aOR 3.14; 95% CI 1.73-5.71), Charlson co-morbidity score (aOR 1.25; 95% CI 1.09-1.44) and age (aOR 1.02; 95% CI 1.01-1.04) were independently associated with increased in-hospital mortality, while >= 200 mg/day polymyxin B was associated with lower risk for this outcome (aOR 0.43; 95% CI 0.23-0.79). The effect of >= 200 mg/day polymyxin B on in-hospital mortality was higher in both subgroups (microbiologically documented infections and bacteraemia). Patients receiving >= 200 mg/day of polymyxin B had significantly higher risk of severe renal impairment.A dosage of >= 200 mg/day polymyxin B was associated with lower in-hospital mortality. The benefit of these higher doses outweighed the risk of severe renal dysfunction during therapy. Large prospective studies including pharmacokinetic/pharmacodynamic analysis are still required to define the best dosage regimens of polymyxin B.