Prophylaxis and treatment of bacterial infections: do we need new strategies?

Alessandra Micozzi, Giampaolo Bucaneve
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Abstract

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.

预防和治疗细菌感染:我们需要新的策略吗?
恶性血液病患者的细菌感染仍然是一个严重的、危及生命的问题。过去十年的几项观察性研究表明,发热中性粒细胞减少患者是一个异质性人群,在对初始治疗的反应、严重并发症的发展和死亡率方面存在各种差异。对中性粒细胞减少作为血液病患者感染的主要危险因素的作用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进行了广泛的研究,并明确了基于感染风险的不同类别的患者,主要是中性粒细胞减少的情况。血液病患者的抗菌治疗和支持性护理策略需要不断评估,事实上,有利于恶性血液病患者发生感染性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是一个有争议的问题。在2005年之前,几项试验表明,预防感染对这类患者极为重要,但没有一项是结论性的。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,表明抗菌药物预防可以降低中性粒细胞减少症患者的几个重要结局,包括死亡率。经验性抗菌治疗的使用代表了发热性中性粒细胞减少症患者抗菌策略的基石,在20年的时间里,死亡率急剧下降:实际上-内酰胺单药治疗通常用于发热性中性粒细胞减少症的经验性治疗。最近,大型随机临床试验和荟萃分析表明,添加氨基糖苷和/或糖肽仅在选定的严重感染中产生更有利的结果。在嗜中性粒细胞减少血液病患者中使用抗生素也应谨慎和安全,以防止微生物耐药性的出现,节省费用,减少毒性。因此,根据证据,抗菌预防应仅限于高危血液病患者,在发热性中性粒细胞减少的情况下,应建议经验性肠外抗生素单药治疗,限制使用淀粉糖苷类和糖肽。在未来,血液病患者应作出重大努力,以说明新的危险因素,可以更准确地确定亚群靶向抗感染策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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