We performed a systematic review of studies that compared beta-lactams vs. beta-lactams plus aminoglycosides for the treatment of febrile neutropenia in cancer patients. Method: We searched CENTRAL, MEDLINE, and Embase for studies published up to October 2023, and randomized controlled trials (RCTs) that compared anti-Pseudomonas aeruginosa beta-lactam monotherapy with any combination of an anti-Pseudomonas aeruginosa beta-lactam and an aminoglycoside were included. Result: The all-cause mortality rate of combination therapy showed no significant differences compared with that of monotherapy (RR 0.99, 95% CI 0.84 to 1.16, high certainty of evidence). Infection-related mortality rates showed that combination therapy had a small positive impact compared with the intervention with monotherapy (RR 0.83, 95% CI 0.66 to 1.05, high certainty of evidence). Regarding treatment failure, combination therapy showed no significant differences compared with monotherapy (RR 0.99, 95% CI 0.94 to 1.03, moderate certainty of evidence). In the sensitivity analysis, the treatment failure data published between 2010 and 2019 showed better outcomes in the same beta-lactam group (RR 1.10 [95% CI, 1.01–1.19]). Renal failure was more frequent with combination therapy of any daily dosing regimen (RR 0.46, 95% CI 0.36 to 0.60, high certainty of evidence). Conclusions: We found combining aminoglycosides with a narrow-spectrum beta-lactam did not spare the use of broad-spectrum antibiotics. Few studies included antibiotic-resistant bacteria and a detailed investigation of aminoglycoside serum levels, and studies that combined the same beta-lactams showed only a minimal impact with the combination therapy. In the future, studies that include the profile of antibiotic-resistant bacteria and the monitoring of serum aminoglycoside levels will be required.
我们对比较β-内酰胺类药物与β-内酰胺类联合氨基糖苷类药物治疗癌症患者发热性中性粒细胞减少症的研究进行了系统综述。方法：我们检索了截至2023年10月发表的CENTRAL、MEDLINE和Embase数据库，纳入了比较抗铜绿假单胞菌β-内酰胺单药疗法与抗铜绿假单胞菌β-内酰胺联合氨基糖苷类任何组合的随机对照试验。结果：联合疗法的全因死亡率与单药疗法相比无显著差异（RR 0.99，95% CI 0.84至1.16，证据确定性高）。感染相关死亡率显示，联合疗法较单药干预有轻微积极影响（RR 0.83，95% CI 0.66至1.05，证据确定性高）。在治疗失败方面，联合疗法与单药疗法相比无显著差异（RR 0.99，95% CI 0.94至1.03，证据确定性中等）。敏感性分析显示，2010年至2019年间发表的治疗失败数据在同种β-内酰胺组中表现出更好的结果（RR 1.10 [95% CI, 1.01–1.19]）。采用任何每日给药方案的联合疗法更易引发肾功能衰竭（RR 0.46，95% CI 0.36至0.60，证据确定性高）。结论：我们发现氨基糖苷类联合窄谱β-内酰胺类药物并不能减少广谱抗生素的使用。现有研究很少纳入耐药菌及详细的氨基糖苷血药浓度监测，且同种β-内酰胺联合治疗的研究显示联合疗法仅产生极小的影响。未来需要开展纳入耐药菌特征及监测氨基糖苷血药浓度的研究。
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