Schimpff S C
Am J Med. 1986 May 30;80(5C):13-20.
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.
许多癌症患者在接受治疗后会出现粒细胞减少症，因此在中性粒细胞减少期可能会发烧。这些病例中约20%伴有革兰氏阴性杆菌血症；这些感染发生在粒细胞极度减少的患者中，且死亡率最高。大多数感染由三种微生物之一引起：大肠杆菌、铜绿假单胞菌或肺炎克雷伯菌。标准的治疗方法是经验性地使用抗生素联合治疗，最常用的是氨基糖苷类药物与抗假单胞菌青霉素或头孢菌素联合使用。对于那些高度关注氨基糖苷类药物相关肾毒性或耳毒性的患者，可考虑使用双β-内酰胺联合治疗。此外，随着越来越高效、超广谱抗菌药物的出现，也有人考虑使用单药进行经验性治疗。β-内酰胺/氨基糖苷类联合用药通常具有协同作用，不过偶尔也会发现拮抗作用。一些双β-内酰胺联合用药表现出拮抗作用，而在其他情况下，则可观察到协同作用或至少部分协同作用。抗生素联合用药可通过体外模型（如毛细管模型系统）或旨在模拟伴有革兰氏阴性杆菌血症的中性粒细胞减少状态的动物模型进行评估，以确定针对该患者群体的潜在药物或药物组合。这些临床前研究方法表明，一些药物可能作为单一疗法有效，实际上，其活性与一些标准抗生素联合用药相当。然而，临床试验中特别高危的、伴有严重持续性粒细胞减少和革兰氏阴性杆菌血症的患者数量不足，无法评估这些药物在这类患者中的有效性。总体而言，使用如欧洲癌症研究与治疗组织最近的抗菌药物试验中所采用的联合用药方案（该试验比较了阿洛西林/阿米卡星与头孢他啶/阿米卡星）似乎仍然是有利的。为了降低氨基糖苷类药物的毒性，患者被随机分配接受短期或全程的阿米卡星治疗。该研究应有助于确定是否有可能在保持两药联合治疗优势的同时，减少氨基糖苷类药物长期治疗的弊端。
