Carbapenem-Resistant Enterobacteriaceae Infections: Results From a Retrospective Series and Implications for the Design of Prospective Clinical Trials.
Carbapenem-Resistant Enterobacteriaceae Infections: Results From a Retrospective Series and Implications for the Design of Prospective Clinical Trials.
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DOI：
10.1093/ofid/ofx063
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发表时间：
2017
影响因子：
4.2
通讯作者：
Dudley MN
中科院分区：
文献类型：
--
作者：
Alexander EL;Loutit J;Tumbarello M;Wunderink R;Felton T;Daikos G;Fusaro K;White D;Zhang S;Dudley MN
多重耐药的革兰氏阴性菌，如耐碳青霉烯类肠杆菌科(CRE)的发生率不断增加，导致对新的抗菌药的迫切需求。大多数新抗菌药的研究都是在非耐药病原体患者身上进行的。我们对CRE感染患者进行了回顾性分析，以指导第三阶段临床试验的设计。这是一项在4个国家的22个中心进行的回顾性研究。收集了合并尿路感染(CUTI)/急性肾盂肾炎(AP)、医院获得性细菌性肺炎(HABP)、呼吸机相关细菌性肺炎(VABP)和CRE所致菌血症的患者的基线数据、治疗和结果。共查出Cre感染256例，其中CUTI/AP 75例，HABP 21例，VABP 20例，菌血症140例。患者群体有显著的合并症：32.8%患有慢性肾功能不全，26.2%免疫功能低下。病情严重程度高：29.3%的患者出现感染性休克。治疗方案千差万别；然而，大多数患者接受了联合治疗。所有感染部位的预后普遍较差(28天死亡率为28.1%)，尤其是在透析患者和败血症患者中。Cre感染发生在有大量并存的患者中，并与高死亡率和低临床治愈率有关。患有这些合并症的患者通常被排除在新药注册的临床试验之外。这些结果导致了3期试验的纳入/排除标准的变化，以更好地代表CRE感染的患者群体，并使登记成为可能。观察性研究在指导临床试验设计、告知现有护理标准以及为后续试验提供外部对照方面可能变得越来越重要。
The increasing incidence of multidrug-resistant Gram negatives, such as carbapenem-resistant Enterobacteriaceae (CRE), has resulted in a critical need for new antimicrobials. Most studies of new antimicrobials have been performed in patients with nondrug-resistant pathogens. We performed a retrospective analysis of patients with CRE infections to inform the design of phase 3 clinical trials. This was a retrospective study at 22 centers in 4 countries. Baseline data, treatment, and outcomes were collected in patients with complicated urinary tract infection (cUTI)/acute pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), and bacteremia due to CRE. Two hundred fifty-six cases of CRE infection were identified: 75 cUTI/AP, 21 HABP, 20 VABP, and 140 bacteremia. The patient population had significant comorbidities: 32.8% had chronic renal insufficiency, and 26.2% were immunocompromised. Illness severity at presentation was high: 29.3% presented with septic shock. Treatment regimens varied widely; however, a majority of patients received combination therapy. Outcomes were universally poor (28-day mortality was 28.1%) across all sites of infection, particularly in dialysis patients and those with sepsis. The CRE infections occured in patients with substantial comorbidities and were associated with high mortality and low rates of clinical cure with available antibiotics. Patients with these comorbidities are often excluded from enrollment in clinical trials for registration of new drugs. These results led to changes in the inclusion/exclusion criteria of a phase 3 trial to better represent the patient population with CRE infections and enable enrollment. Observational studies may become increasingly important to guide clinical trial design, inform on the existing standard of care, and provide an external control for subsequent trials.