替加环素在治疗复杂性腹腔内感染方面有效。
Tigecycline is efficacious in the treatment of complicated intra-abdominal infections.
作者信息
Fomin Peter, Beuran Mircea, Gradauskas Audrius, Barauskas Giedrius, Datsenko Alexey, Dartois Nathalie, Ellis-Grosse Evelyn, Loh Evan
机构信息
National Medical University, Surgical Department, City Hospital No 12, Podvysotskogo Street 4-a, 01 103 Kyiv, Ukraine.
出版信息
Int J Surg. 2005;3(1):35-47. doi: 10.1016/j.ijsu.2005.03.011.
BACKGROUND
Empiric treatment of complicated intra-abdominal infections (cIAI) represents a clinical challenge because of the diverse bacteriology and the emergence of bacterial resistance. The efficacy and safety of tigecycline (TGC), a first-in-class, expanded broad-spectrum glycylcycline antibiotic, were compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI.
METHODS
In this prospective, double-blind, phase 3, multinational trial, patients were randomly assigned to intravenous (i.v.) TGC (100 mg initial dose, then 50 mg every 12 h) or i.v. IMI/CIS (500/500 mg every 6 h) for 5-14 days. Clinical response was assessed at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiologically modified intent-to-treat (m-mITT) populations (co-primary efficacy endpoint populations in which cure/failure response rates were determined).
RESULTS
Of 817 mITT patients (i.e., received > or = 1 dose of study drug), 641 (78%) comprised the m-mITT cohort (322 TGC, 319 IMI/CIS) and 523 (64%) were ME (266 TGC, 256 IMI/CIS). Patients were predominantly white (88%) and male (59%) with a mean age of 49 years. The primary diagnoses for the mITT group were complicated appendicitis (41%), cholecystitis (22%), and intra-abdominal abscess (11%). For the ME population, clinical cure rates at TOC were 91.3% (242/265) for TGC versus 89.9% (232/258) for IMI/CIS (95% CI -4.0, 6.8; P<0.001). Corresponding clinical cure rates within the m-mITT population were 86.6% (279/322) for TGC versus 84.6% (270/319) for IMI/CIS (95% CI -3.7, 7.5; P<0.001 for noninferiority TGC versus IMI/CIS). The most commonly reported adverse events for TGC and IMI/CIS were nausea (17.6% TGC versus 13.3% IMI/CIS; P=0.100) and vomiting (12.6% TGC versus 9.2% IMI/CIS; P=0.144).
CONCLUSIONS
TGC is efficacious in the treatment of patients with cIAIs and TGC met per the protocol-specified statistical criteria for noninferiority to the comparator, IMI/CIS.
背景
由于复杂腹腔内感染（cIAI）的细菌学多样且细菌耐药性不断出现，其经验性治疗面临临床挑战。将首个获批的、具有扩大的广谱抗菌活性的甘氨酰环素类抗生素替加环素（TGC）与亚胺培南/西司他丁（IMI/CIS）在cIAI患者中的疗效及安全性进行比较。
方法
在这项前瞻性、双盲、3期、多国试验中，患者被随机分配接受静脉注射TGC（首剂100mg，随后每12小时50mg）或静脉注射IMI/CIS（每6小时500/500mg），疗程5 - 14天。在治疗结束访视（TOC，治疗后14 - 35天）时对微生物学可评估（ME）人群和微生物学改良意向性治疗（m - mITT）人群（确定治愈/失败反应率的共同主要疗效终点人群）评估临床反应。
结果
在817例意向性治疗（ITT）患者（即接受≥1剂研究药物）中，641例（78%）构成m - mITT队列（322例TGC，319例IMI/CIS），523例（64%）为ME人群（266例TGC，256例IMI/CIS）。患者主要为白人（88%）和男性（59%），平均年龄49岁。ITT组的主要诊断为复杂性阑尾炎（41%）、胆囊炎（22%）和腹腔内脓肿（11%）。对于ME人群，TOC时TGC的临床治愈率为91.3%（242/265），而IMI/CIS为89.9%（232/258）（95%CI -4.0，6.8；P<0.001）。m - mITT人群中TGC和IMI/CIS相应的临床治愈率分别为86.6%（279/322）和84.6%（270/319）（TGC相对于IMI/CIS非劣效性的95%CI -3.7，7.5；P<0.001）。TGC和IMI/CIS最常报告的不良事件为恶心（TGC为17.6%，IMI/CIS为13.3%；P = 0.100）和呕吐（TGC为12.6%，IMI/CIS为9.2%；P = 0.144）。
结论
TGC在治疗cIAI患者中有效，且根据方案规定的统计标准，TGC相对于对照药物IMI/CIS具有非劣效性。
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