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Once-Daily Plazomicin for Complicated Urinary Tract Infections

Florian M.E. Wagenlehner ... 传染病 • 2019.02.21
• 无发热男性尿路感染患者的抗生素疗程






我们以1∶1的比例将609例复杂性尿路感染(UTI;包括急性肾盂肾炎)患者随机分组,分别接受plazomicin(每日1次,每次15 mg/kg体重)或美罗培南(每8小时1 g)静脉治疗,并且在至少4日的静脉治疗后可以选择采用降级口服治疗(oral step-down therapy),总共治疗7~10日。主要目的是证明在复杂性UTI(包括急性肾盂肾炎)的治疗中,plazomicin不劣于美罗培南,非劣效性界值为15个百分点。主要终点是在微生物学改良意向治疗人群中,第5日和治愈验证(test-of-cure)访视(治疗开始后15~19日)时的复合治愈(临床治愈并且微生物学根除)。



对于主要疗效终点,plazomicin不劣于美罗培南。第5日时,在plazomicin组88.0%的患者(191例患者中的168例)和美罗培南组91.4%的患者(197例患者中的180例)中观察到复合治愈(差异,-3.4个百分点;95%置信区间[CI],-10.0~3.1)。治愈验证访视时,分别在81.7%(191例患者中的156例)和70.1%(197例患者中的138例)的患者中观察到复合治愈(差异,11.6个百分点;95% CI,2.7~20.3)。治愈验证访视时,plazomicin组微生物学根除的患者百分比高于美罗培南组,包括对氨基糖苷类药物不敏感的肠杆菌(78.8% vs. 68.6%)和产超广谱β-内酰胺酶的肠杆菌(82.4% vs. 75.0%)的根除。后期随访时(治疗开始后24~32日),与美罗培南组相比,plazomicin组微生物学复发(3.7% vs. 8.1%)或临床复发(1.6% vs. 7.1%)的患者较少。plazomicin组7.0%患者和美罗培南组4.0%患者的血清肌酐水平升高至比基线水平高≥0.5 mg/dL(≥40 μmol/L)。



对于肠杆菌(包括耐多药菌株)引起的复杂性UTI和急性肾盂肾炎的治疗,plazomicin每日1次用药不劣于美罗培南(由Achaogen和美国生物医学高级研究与发展管理局[Biomedical Advanced Research and Development Authority]资助;EPIC在ClinicalTrials.gov注册号为NCT02486627)。


Florian M.E. Wagenlehner, M.D., Daniel J. Cloutier, Pharm.D., Allison S. Komirenko, Pharm.D., Deborah S. Cebrik, M.S., M.P.H., Kevin M. Krause, M.B.A., Tiffany R. Keepers, Ph.D., Lynn E. Connolly, M.D., Ph.D., Loren G. Miller, M.D., M.P.H., Ian Friedland, M.D., and Jamie P. Dwyer, M.D. for the EPIC Study Group*
From the Justus Liebig University, Giessen, Germany (F.M.E.W.); Achaogen, South San Francisco (D.J.C., A.S.K., D.S.C., K.M.K., T.R.K., L.E.C., I.F.), the David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles (L.G.M.), and Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance (L.G.M.) — all in California; and Vanderbilt University Medical Center, Nashville (J.P.D.). Address reprint requests to Dr. Wagenlehner at the Clinic for Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Rudolf-Buchheim Str. 7, 35392 Giessen, Germany, or at florian.wagenlehner@chiru.med.uni-giessen.de. *A complete list of the principal investigators in the EPIC Study is provided in the Supplementary Appendix, available at NEJM.org.



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