DeJace P, Klastersky J
Am J Med. 1986 Jun 30;80(6B):29-38. doi: 10.1016/0002-9343(86)90476-6.
Febrile neutropenic patients are usually treated with a combination of a beta-lactam and an aminoglycoside. Since Pseudomonas aeruginosa is an important pathogen in these patients, the empiric use of possibly synergistic combinations against that organism has been traditionally recommended. The recent appearance of beta-lactams more active against P. aeruginosa and the well-known nephrotoxicity of aminoglycosides have led some to advocate the use of beta-lactam combinations for empiric treatment of fever in neutropenic cancer patients. This article reviews the available literature on the controlled use of combinations of beta-lactams in the treatment of febrile neutropenic patients as compared with that of combinations of beta-lactams and aminoglycosides. The review includes comparison of overall response, response in patients with septicemia or other infections, response associated with different pathogens, the effect of profound neutropenia, and an evaluation of the toxicities encountered. Overall, these results show that response rates with a combination of two beta-lactams are similar to those obtained with the combinations of a beta-lactam and an aminoglycoside for infections in patients with serious underlying disease and compromised mechanisms of defense. They also suggest that the steady emergence of resistance of pathogens to beta-lactams has often been overcome by the use of newer drugs in regard to infections caused by the Enterobacteriaceae but much less effectively in regard to P. aeruginosa. There are still important theoretic reasons for preferring an aminoglycoside-containing combination as empiric therapy in febrile neutropenic patients, and our overall conclusion is that it would be appropriate to conduct a large-scale trial comparing beta-lactam combinations with the traditional beta-lactam plus aminoglycoside regimens in that setting.
发热性中性粒细胞减少患者通常接受β-内酰胺类药物和氨基糖苷类药物联合治疗。由于铜绿假单胞菌是这些患者的重要病原体，传统上推荐经验性使用可能对该菌具有协同作用的联合用药方案。近年来出现了对铜绿假单胞菌活性更强的β-内酰胺类药物，且氨基糖苷类药物具有众所周知的肾毒性，这使得一些人主张使用β-内酰胺类联合用药方案对中性粒细胞减少的癌症患者进行发热的经验性治疗。本文回顾了与β-内酰胺类药物和氨基糖苷类药物联合用药相比，β-内酰胺类药物联合用药在治疗发热性中性粒细胞减少患者方面的现有文献。该综述包括总体反应、败血症或其他感染患者的反应、不同病原体相关的反应、严重中性粒细胞减少的影响以及所遇到毒性的评估。总体而言，这些结果表明，对于患有严重基础疾病和防御机制受损的患者的感染，两种β-内酰胺类药物联合使用的反应率与β-内酰胺类药物和氨基糖苷类药物联合使用的反应率相似。它们还表明，对于肠杆菌科细菌引起的感染，病原体对β-内酰胺类药物耐药性的不断出现常常可以通过使用更新的药物来克服，但对于铜绿假单胞菌引起的感染，效果则要差得多。在发热性中性粒细胞减少患者中，仍有重要的理论依据支持首选含氨基糖苷类药物的联合用药方案作为经验性治疗，我们的总体结论是，在这种情况下进行一项大规模试验，比较β-内酰胺类联合用药方案与传统的β-内酰胺类加氨基糖苷类用药方案是合适的。
