Fomin P, Koalov S, Cooper A, Babinchak T, Dartois N, De Vane N, Castaing N, Tellado J
National Medical University, Kyiv, Ukraine.
J Chemother. 2008 Oct;20 Suppl 1:12-9. doi: 10.1179/joc.2008.20.Supplement-1.12.
The polymicrobial nature of complicated intra-abdominal infections makes these infections particularly challenging to treat. The initial selection of antimicrobial therapy is therefore extremely important. Inappropriate empiric antimicrobial therapy has been shown to delay clinical resolution, increase length of hospital stay, and increase the risk of mortality. In addition, the increasing frequency with which resistant isolates (e.g., extended spectrum beta-lactamases [ESBLs]) are recovered from patients mandates that empiric antimicrobial therapy covers these difficult-to-treat organisms. Here, we assessed the efficacy of a new antimicrobial agent, tigecycline. This is a combined analysis of data from the European sites that participated in two Phase III, double-blind trials to evaluate the efficacy and safety of tigecycline, versus that of imipenem/cilastatin, in adults with complicated intra-abdominal infections. Patients received either tigecycline (initial dose of 100 mg, followed by 50 mg intravenously every 12 hours) or imipenem/cilastatin (500/500 mg intravenously every 6 hours) for 5-14 days. The primary end point was the clinical response at the test-of-cure visit (12-44 days after therapy) in the co-primary microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations. For the ME group, clinical cure rates at the test-of-cure visit were 92.4% (219/237) for tigecycline versus 88.8% (198/223) for imipenem/cilastatin (95% CI = -2.2, 9.4). Clinical cure rates for the mmITT populations were 87.3% (247/283) for tigecycline versus 83.5% (228/273) for imipenem/cilastatin (95% CI = -2.5, 10.0) at the test-of-cure visit. Pretherapy in vitro activity against baseline isolates for tigecycline and imipenem/cilastatin were also determined. The mean MIC(90) for tigecycline against the most commonly isolated aerobes and anaerobes was < or =2.0 microg/mL. No pretherapy isolates displayed resistance to tigecycline based on the breakpoints used. Bacterial susceptibilities to tigecycline appeared to be consistent with clinical responses. Most commonly reported treatment emergent adverse events for tigecycline and imipenem/cilastatin were nausea (14.7% and 11.8%, respectively, p = 0.267) and vomiting (10.7% and 7.3%, respectively p = 0.146). This combined analysis demonstrates that tigecycline is safe and effective for the treatment of complicated intra-abdominal infections, and reflects the findings of the global population.
复杂性腹腔内感染的多微生物性质使得这些感染的治疗极具挑战性。因此，抗菌治疗的初始选择极为重要。已证实不恰当的经验性抗菌治疗会延迟临床缓解、增加住院时间并增加死亡风险。此外，从患者中分离出耐药菌株（如超广谱β-内酰胺酶[ESBLs]）的频率不断增加，这就要求经验性抗菌治疗覆盖这些难以治疗的病原体。在此，我们评估了一种新型抗菌药物替加环素的疗效。这是一项对参与两项III期双盲试验的欧洲研究点的数据进行的综合分析，目的是评估替加环素与亚胺培南/西司他丁相比，在患有复杂性腹腔内感染的成人患者中的疗效和安全性。患者接受替加环素（初始剂量100mg，随后每12小时静脉注射50mg）或亚胺培南/西司他丁（每6小时静脉注射500/500mg）治疗5 - 14天。主要终点是在共同主要的微生物学可评估（ME）和微生物学改良意向性治疗（m - mITT）人群中，在治疗结束访视（治疗后12 - 44天）时的临床反应。对于ME组，在治疗结束访视时，替加环素的临床治愈率为92.4%（219/237），而亚胺培南/西司他丁为88.8%（198/223）（95%CI = -2.2，9.4）。在治疗结束访视时，m - mITT人群中替加环素的临床治愈率为87.3%（247/283），亚胺培南/西司他丁为83.5%（228/273）（95%CI = -2.5，10.0）。还测定了替加环素和亚胺培南/西司他丁对基线分离株的治疗前体外活性。替加环素对最常见分离的需氧菌和厌氧菌的平均MIC(90)≤2.0μg/mL。根据所使用的断点，没有治疗前分离株对替加环素显示耐药。细菌对替加环素的敏感性似乎与临床反应一致。替加环素和亚胺培南/西司他丁最常报告的治疗中出现的不良事件是恶心（分别为14.7%和11.8%，p = 0.267）和呕吐（分别为10.7%和7.3%，p = 0.146）。这项综合分析表明，替加环素治疗复杂性腹腔内感染安全有效，并反映了全球人群的研究结果。
