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超声引导下替加环素联合抗生素治疗显著提高了急性髓系白血病诱导缓解含阿糖胞苷化疗后中性粒细胞减少性小肠结肠炎患者的生存率。

Ultrasonography-driven combination antibiotic therapy with tigecycline significantly increases survival among patients with neutropenic enterocolitis following cytarabine-containing chemotherapy for the remission induction of acute myeloid leukemia.

作者信息

Pugliese Novella, Salvatore Paola, Iula Dora Vita, Catania Maria Rosaria, Chiurazzi Federico, Della Pepa Roberta, Cerchione Claudio, Raimondo Marta, Giordano Claudia, Simeone Luigia, Caruso Simona, Pane Fabrizio, Picardi Marco

机构信息

Departments of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy.

Molecular Medicine and Medical Biotechnology, Federico II University Medical School, Naples, Italy.

出版信息

Cancer Med. 2017 Jul;6(7):1500-1511. doi: 10.1002/cam4.1063. Epub 2017 May 26.

Abstract

Neutropenic enterocolitis (NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia (AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100-6000 mg/m daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high-dose cytarabine, whereas 19% and 15% intermediate-dose and standard-dose cytarabine, respectively (P < 0.001). The 30-day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality (P < 0.001); whereas, standard-dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high-dose cytarabine-containing chemotherapy was the independent predictor of poor outcome (odds ratio [OR]: 0.109; 95% confidence interval [CI]: 0.032-0.364; P < 0.001), whereas ultrasonography-driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome (OR: 13.161; 95% CI: 1.587-109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic findings, with drug combinations which have broad antimicrobial coverage and good gut penetration, specifically those also including tigecycline, may be effective in improving 30-day survival rate after NEC onset.

摘要

中性粒细胞减少性小肠结肠炎(NEC)是一种主要在接受化疗(尤其是阿糖胞苷,一种对急性髓系白血病(AML)缓解有效的细胞毒性药物)后的AML患者中报道的腹部感染。关于不同阿糖胞苷给药方案和/或抗菌方案对NEC影响的具体数据很少。本研究的目的是确定NEC发病后30天内的预后预测因素。回顾性地在我们机构10年间住院接受每日100 - 6000mg/m阿糖胞苷化疗方案的440例新诊断AML患者中找出NEC发作病例。通过逻辑回归分析比较了两个亚组,即存活者与非存活者。在420例分析患者中有100例(23.8%)记录有NEC:42.5%接受了高剂量阿糖胞苷,而接受中剂量和标准剂量阿糖胞苷的分别为19%和15%(P < 0.001)。NEC导致的30天死亡率为23%。单因素分析中,含高剂量阿糖胞苷的抗白血病方案与高死亡率显著相关(P < 0.001);而标准剂量阿糖胞苷以及在肠道壁增厚超声表现时立即开始使用包括替加环素在内的抗生素联合治疗NEC与低死亡率显著相关。多因素分析中,含高剂量阿糖胞苷的化疗是预后不良的独立预测因素(比值比[OR]:0.109;95%置信区间[CI]:0.032 - 0.364;P < 0.001),而超声引导下使用包括替加环素在内的抗生素方案治疗NEC与良好预后相关(OR:13.161;95% CI:1.587 - 109.17;P = 0.017)。用于AML缓解的含高剂量阿糖胞苷的化疗方案与高NEC发生率及归因率相关。基于病理超声检查结果启动的强力抗菌治疗,使用具有广泛抗菌谱和良好肠道穿透性的药物联合,特别是那些也包括替加环素的联合用药,可能有效提高NEC发病后30天的生存率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a8d/5504336/649869a58b4f/CAM4-6-1500-g001.jpg

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