Micozzi Alessandra, Bucaneve Giampaolo
Dipartimento di Biotecnologie ed Ematologia Ematologia, Università La Sapienza, Roma.
Rev Clin Exp Hematol. 2005 Dec;9(2):E4.
Bacterial infections in patients with hematologic malignancies still represent a severe and life-treating problem. Several observational studies during the last decade have revealed that neutropenic patients with fever are a heterogeneous population with various differences regarding response to initial therapy, development of serious complications and mortality. The role of neutropenia as main risk factor for infections in hematologic patients and the definition of different level of risk related to neutrophils count and duration of neutropenia have been extensively studied and different categories of patients based on the risk of infection, mostly the condition of neutropenia, have been clearly defined. The strategies on antimicrobial therapy and supportive care in hematologic patients need to be continuously assessed, in fact new conditions favouring the occurrence of infectious complications in patients with hematologic malignancies have progressively emerged. The use of oral prophylactic antibiotics in neutropenic cancer patients is still a matter of debate. Before 2005, several trials showed how the prevention of infection can be extremely important in this setting of patients but none was conclusive. In 2005 two meta-analysis and two large randomized clinical trials gave new evidence that antibacterial prophylaxis can reduce in neutropenic patients several important outcomes including mortality. The use of the empiric antibacterial therapy represents the cornerstone of the antimicrobial strategies in the febrile neutropenic patients leading, over the span of 20 years, to a dramatic decrease of deaths: Actually beta-lactam monotherapy is commonly used for the empiric treatment of febrile neutropenia. Recently, large randomized clinical trials and meta-analysis showed that the addition of an aminoglycoside and/or a glycopeptides results in a more favourable outcome only in selected severe infections. The use of antibiotics should be prudent and safe also in neutropenic hematologic patients to prevent emergence of microbial resistance, to save costs, to reduce toxicity. For this reasons, according to the evidence, antibacterial prophylaxis should be restricted to high risk hematologic patients and empiric parenteral antibiotic monotherapy should be recommended in case of febrile neutropenia limiting the use of amynoglicosides and glycopeptides. In the next future, a major effort should be made to state in hematologic patients new risk factors which could more accurately define subgroups for targeted anti-infective strategies.
血液系统恶性肿瘤患者的细菌感染仍然是一个严重且危及生命的问题。过去十年的多项观察性研究表明,发热的中性粒细胞减少患者是一个异质性群体,在初始治疗反应、严重并发症的发生和死亡率方面存在各种差异。中性粒细胞减少作为血液系统疾病患者感染的主要危险因素,以及与中性粒细胞计数和中性粒细胞减少持续时间相关的不同风险水平的定义,已经得到了广泛研究,并且基于感染风险,主要是中性粒细胞减少的情况,明确划分了不同类别的患者。血液系统疾病患者的抗菌治疗和支持治疗策略需要持续评估,事实上,有利于血液系统恶性肿瘤患者发生感染并发症的新情况已逐渐出现。在中性粒细胞减少的癌症患者中使用口服预防性抗生素仍然存在争议。2005年之前,多项试验表明在这类患者中预防感染极为重要,但均无定论。2005年,两项荟萃分析和两项大型随机临床试验提供了新的证据,表明抗菌预防可降低中性粒细胞减少患者的多项重要结局,包括死亡率。经验性抗菌治疗是发热性中性粒细胞减少患者抗菌策略的基石,在20年的时间里,导致死亡人数大幅下降:实际上,β-内酰胺单药治疗常用于发热性中性粒细胞减少的经验性治疗。最近,大型随机临床试验和荟萃分析表明,仅在某些严重感染中添加氨基糖苷类和/或糖肽类药物会带来更有利的结果。在中性粒细胞减少的血液系统疾病患者中使用抗生素也应谨慎且安全,以防止微生物耐药性的出现、节省成本、降低毒性。因此,根据现有证据,抗菌预防应仅限于高危血液系统疾病患者,发热性中性粒细胞减少时应推荐经验性肠外抗生素单药治疗,限制氨基糖苷类和糖肽类药物的使用。在未来,应做出重大努力,确定血液系统疾病患者的新危险因素,从而更准确地界定有针对性抗感染策略的亚组。