Empiric antibiotic therapy for granulocytopenic cancer patients.
Empiric antibiotic therapy for granulocytopenic cancer patients.
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粒细胞减少性癌症患者的经验性抗生素治疗。
DOI：
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发表时间：
1986
期刊：
影响因子：
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通讯作者：
Schimpff Sc
中科院分区：
文献类型：
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作者：
Schimpff Sc
摘要许多癌症患者由于治疗而出现粒细胞减少症，因此，在粒细胞减少症发作期间可能会发热。其中大约20%的病例伴有相关的革兰氏阴性杆菌血症;这些感染发生在最严重的粒细胞减少症患者中，并且死亡率最高。大多数感染是由以下三种微生物之一引起的：大肠杆菌、铜绿假单胞菌或肺炎克雷伯菌。治疗的标准方法是经验性地使用抗生素组合，最常见的是氨基糖苷类抗生素与抗假单胞菌青霉素或头孢菌素的组合。对于高度关注氨基糖苷类药物相关肾毒性或耳毒性的患者，可考虑双β-内酰胺联合给药。此外，随着越来越多的活性，特别是广谱抗菌药物的引入，已考虑使用单一药物的经验性治疗。β-内酰胺类/氨基糖苷类联合用药通常具有协同作用，尽管有时可检测到拮抗作用。一些双β-内酰胺组合表现出拮抗作用，而在其他情况下，可以观察到协同作用或至少部分协同作用。抗生素组合可通过体外模型（如毛细血管模型系统）或通过设计用于模拟具有革兰氏阴性菌血症的血小板减少状态的动物模型进行评估，以确定用于该患者群体的潜在药剂或药剂组合。这些临床前方法表明，一些药物可能被证明是有效的单一疗法，而且实际上，在活性上与一些标准抗生素组合相当。然而，临床试验没有足够数量的特别高风险的患者，严重的，持续的粒细胞减少症和革兰氏阴性杆菌血症，能够评估他们在这些患者中的有用性。一般来说，使用诸如在最近的欧洲癌症治疗研究组织抗微生物试验中使用的那些组合似乎仍然是有利的，该试验将阿洛西林/阿米卡星与头孢他啶/阿米卡星进行了比较。为了减少氨基糖苷类药物的毒性，患者被随机分配接受阿米卡星短期或整个治疗时间。这项研究应该有助于确定是否有可能保持两种药物联合治疗的优点，同时减少长期氨基糖苷类药物治疗的缺点。
Abstract Many cancer patients become granulocytopenic as a result of therapy and, as such, are likely to have fever during neutropenic episodes. Approximately 20 percent of these episodes have an associated gram-negative rod bacteremia; these infections occur among the most profoundly granulocytopenic patients and are associated with the highest mortality. Most infections are caused by one of three organisms: Escherichia coli, Pseudomonas aeruginosa, or Klebsiella pneumoniae. The standard approach to therapy has been the empiric utilization of an antibiotic combination, most often an aminoglycoside with either an anti-Pseudomonas penicillin or a cephalosporin. In patients for whom concern about aminoglycoside-associated nephro- or ototoxicity is high, a double beta-lactam combination has been considered. Also, with the introduction of increasingly active, exceptionally broad-spectrum antimicrobials, empiric therapy with single agents has been considered. Beta-lactam/aminoglycoside combinations more often than not are synergistic, although antagonism can be detected on occasion. Some double beta-lactam combinations demonstrate antagonism, whereas in other cases, synergism, or at least partial synergism, can be observed. Antibiotic combinations can be evaluated through in vitro models, such as the capillary model system, or through animal models designed to mimic the neutropenic state with gram-negative bacteremia, to determine potential agents or combinations of agents for this patient population. These preclinical approaches have suggested that some agents may prove effective as monotherapy and, indeed, have been comparable in activity to some of the standard antibiotic combinations. However, clinical trials have had insufficient numbers of particularly high-risk patients with profound, persistent granulocytopenia and gram-negative rod bacteremia to be able to assess their usefulness in such patients. In general, it still appears to be advantageous to use combinations such as those used in the most recent European Organization for Research on Treatment of Cancer antimicrobial trial, which compared azlocillin/amikacin with ceftazidime/amikacin. In order to reduce aminoglycoside toxicity, patients were randomly assigned to receive amikacin either for a short period or for the entire length of therapy. The study should help to determine whether it is possible to maintain the advantages of two-drug combinations while reducing the disadvantages of prolonged aminoglycoside therapy.