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[中性粒细胞减少症的抗菌预防与治疗]

[Antimicrobial prophylaxis and therapy in neutropenia].

作者信息

Link H

机构信息

Westpfalz-Klinikum, Medizinische Klinik 1, Hellmut-Hartert-Str. 1, D-67655 Kaiserslautern.

出版信息

Mycoses. 2003;46 Suppl 2:21-32.

PMID:15055140
Abstract

Cytostatic chemotherapy of hematological malignancies if often complicated by neutropenia, which increases the risk of infections, especially if the neutrophil count is below 500/ml. Frequently, fever is the first and in most patients the only sign of an infection. Unexplained fever is defined as follows: temperature of > or = 38.3 degrees C or > or = 38.0 degrees C for at least one hour, or measured twice within 12 hours, if the neutrophil count is < 500/ml or < 1.000/ml with predicted decline to 500/ml. Different risk categories can be identified according to the duration of neutropenia: low risk < or = 5 days, intermediate risk 6-9 days, high risk > or = 10 days. An empirical mono- or duotherapy with antipseudomonal and antistreptococcal agents should be initiated immediately. In the low risk patient group, oral therapy with cipro-, levo-, or ofloxacin combined with amoxicillin/clavulanic acid is permissible. For standard and high risk patients, monotherapy can be carried out with either ceftazidime, cefepime, piperacillin with a beta-lactam-inhibitor or a carbapenem. In duo-therapy, a single dose of an aminoglycoside is combined with acylaminopenicillin or a cephalosporin of the third or fourth generation. The addition of glycopeptides in empirical therapy should only be considered in the presence of severe mucositis, or if a catheter-associated infection is suspected. If fever persists after 72-96 hours of first-line therapy with antibiotics, the regimen should be modified (with the exception of e.g. coagulase-negative staphylococci infections, because these infections take longer to respond). Intermediate risk patients should additionally receive an aminoglycoside after monotherapy (penicillin or a cephalosporin). If a carbepenem was administered for monotherapy, this can be followed by a quinolone and/or a glycopeptide. In the high risk group, the same modifications should be made as in the intermediate risk group but with additional systemic antifungal treatment. In the presence of unexplained fever, fluconazole can be administered at first, but if this fails, amphotericin B (conventional or liposomal), voriconazole, itraconazole or caspofungin should be started. After defervescence to < 38 degrees C, treatment should be continued for seven days if the neutrophil count is < 1.000/ml, and for two days if the neutrophil count is > 1.000/ml. In documented infections treatment is directed against the responsible pathogen, however maintaining the broad spectrum activity. Lung infiltrates are often caused by fungal organisms, therefore an empiric antifungal therapy is necessary which is active against Aspergillus species. Antibacterial prophylaxis can reduce the incidence of bacterial infections, but not the mortality by infections. If the risk of fungal infections exceeds 15%, an antifungal prophylaxis with resorbable drugs can be given.

摘要

血液系统恶性肿瘤的细胞毒性化疗常并发中性粒细胞减少症,这会增加感染风险,尤其是当中性粒细胞计数低于500/ml时。发热通常是感染的首个症状,且在大多数患者中是唯一症状。不明原因发热的定义如下:体温≥38.3℃或≥38.0℃持续至少1小时,或在12小时内测量两次,前提是中性粒细胞计数<500/ml或<1000/ml且预计会降至500/ml。根据中性粒细胞减少症的持续时间可确定不同的风险类别:低风险≤5天,中风险6 - 9天,高风险≥10天。应立即开始使用抗假单胞菌和抗链球菌药物进行经验性单药或联合治疗。在低风险患者组中,可采用环丙沙星、左氧氟沙星或氧氟沙星联合阿莫西林/克拉维酸进行口服治疗。对于标准风险和高风险患者,单药治疗可使用头孢他啶、头孢吡肟、哌拉西林加β-内酰胺酶抑制剂或碳青霉烯类药物。联合治疗时,单剂量氨基糖苷类药物与酰氨基青霉素或第三代或第四代头孢菌素联合使用。经验性治疗中添加糖肽类药物仅应在存在严重粘膜炎或怀疑有导管相关感染时考虑。如果在使用抗生素进行一线治疗72 - 96小时后发热仍持续,应调整治疗方案(凝固酶阴性葡萄球菌感染等情况除外,因为这些感染起效较慢)。中风险患者在单药治疗(青霉素或头孢菌素)后应额外加用氨基糖苷类药物。如果单药治疗使用了碳青霉烯类药物,后续可使用喹诺酮类和/或糖肽类药物。在高风险组中,应进行与中风险组相同的调整,但需额外进行全身抗真菌治疗。在不明原因发热的情况下,可首先使用氟康唑,但如果治疗无效,应开始使用两性霉素B(常规或脂质体)、伏立康唑、伊曲康唑或卡泊芬净。体温降至<38℃后,如果中性粒细胞计数<1000/ml,治疗应持续7天;如果中性粒细胞计数>1000/ml,治疗应持续2天。在确诊感染时,治疗应针对致病病原体,但要保持广谱活性。肺部浸润常由真菌引起,因此需要进行针对曲霉菌属的经验性抗真菌治疗。抗菌预防可降低细菌感染的发生率,但不能降低感染导致的死亡率。如果真菌感染风险超过15%,可给予可吸收药物进行抗真菌预防。

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