Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with Hematologic malignancy who have zygomycosis
Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with Hematologic malignancy who have zygomycosis
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DOI：
10.1086/590004
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发表时间：
2008-08-15
影响因子：
11.8
通讯作者：
Kontoyiannis, Dimitrios P.
中科院分区：
文献类型：
--
作者：
Chamilos, Georgios;Lewis, Russell E.;Kontoyiannis, Dimitrios P.
背景资料。接合霉菌病是一种新出现的机会性霉菌病，发生在免疫功能低下的患者中，预后特别差。我们分析了1989-2006年间，在我所连续70名患有合霉菌病的恶性血液病患者中，延迟有效的两性霉素B治疗对预后的影响。我们使用分类和回归树分析来确定早期治疗和延迟治疗之间的死亡率临界点。以两性霉素B为基础的延迟治疗(即在确诊后6天开始治疗)导致确诊后12周的死亡率是早期治疗(82.9%对48.6%)的两倍；在研究的这些年中，这一点保持不变，在多变量分析中是不良结果的独立预测因素(优势比，8.1；95%可信区间，1.7-38.2；P=.008)。被诊断为感染时的活动性恶性肿瘤(P=.003)和单核细胞减少(P=.01)也独立地与不良预后相关，而挽救泊沙康唑治疗(P=.01)和中性粒细胞恢复(P=.009)则预示着良好的预后。由于很难及时区分接合霉菌病和曲霉病，因此对于合并真菌病风险较高的血液系统恶性肿瘤患者，应考虑采取积极的诊断策略，并及时应用具有抗接合霉菌活性的抗真菌药物。
Background. Zygomycosis is an emerging opportunistic mycosis among immunocompromised patients with a particularly poor prognosis.Methods. We analyzed the impact of delaying effective amphotericin B-based therapy on outcome among 70 consecutive patients with hematologic malignancy who had zygomycosis in our institution during the period 1989-2006. We used classification and regression tree analysis to identify the mortality breakpoint between early and delayed treatment.Results. Delayed amphotericin B-based therapy (i.e., initiating treatment >= 6 days after diagnosis) resulted in a 2-fold increase in mortality rate at 12 weeks after diagnosis, compared with early treatment (82.9% vs. 48.6%); this remained constant across the years of the study and was an independent predictor of poor outcome (odds ratio, 8.1; 95% confidence interval, 1.7-38.2;P = .008 ) in multivariate analysis. Active malignancy (P = .003) and monocytopenia (P = .01) at the time of diagnosis of infection were also independently associated with a poor outcome, whereas salvage posaconazole-based therapy (P = .01) and neutrophil recovery (P = .009) were predictive of a favorable outcome.Conclusions. Because discriminating between zygomycosis and aspergillosis in a timely fashion is difficult, the pursuit of aggressive diagnostic strategies and prompt initiation of antifungal agents with activity against Zygomycetes should be considered for patients with hematological malignancy who are at an increased risk for zygomycosis.