Infectious Diseases Division, University of Nebraska Medical Center, Omaha, NE 68198-5400, USA.
J Antimicrob Chemother. 2011 Jun;66(6):1207-9. doi: 10.1093/jac/dkr138. Epub 2011 Apr 6.
Cefepime hydrochloride is approved for pneumonia, empirical therapy for febrile neutropenia, uncomplicated and complicated urinary tract infections, uncomplicated skin and skin structure infections and complicated intra-abdominal infections. A recent meta-analysis by Yahav et al. (Lancet Infect Dis 2007; 7: 338-48) concluded that cefepime was associated with a statistically significant increase in mortality (risk ratio 1.26, 95% confidence interval 1.08-1.49) when compared with other antibiotics. The US FDA decided to re-evaluate the meta-analysis data in collaboration with the drug sponsor. Two years later the FDA Alert summarized that 'data do not indicate a higher rate of death in cefepime-treated patients. Cefepime remains an appropriate therapy for its approved indications.' However, a thorough evaluation of the 52-page FDA report still shows that safety remains an unresolved issue. A Bayesian re-appraisal of the findings by the FDA and by Yahav et al. indicates that there is a 90.9% (by FDA trial-level meta-analysis), 80.8% (by FDA patient-level meta-analysis) and 99.2% (by Yahav et al. meta-analysis) probability that cefepime raises mortality in neutropenic fever patients, which translates into the following numbers needed to harm (NNH), i.e. to cause one extra death with the use of cefepime: FDA trial-level meta-analysis, NNH = 109; FDA patient-level meta-analysis, NNH = 76; Yahav et al. meta-analysis, NNH = 54. A similar harmful probability was observed with skin structure infections but not with pneumonias, intra-abdominal infections and urinary tract infections. In conclusion, cefepime should be avoided in patients with neutropenic fever or with skin structure infections.
盐酸头孢吡肟已获批准用于肺炎、发热性中性粒细胞减少症的经验性治疗、单纯性和复杂性尿路感染、单纯性皮肤和皮肤结构感染以及复杂性腹腔内感染。Yahav 等人最近的一项荟萃分析（Lancet Infect Dis 2007; 7: 338-48）得出结论，与其他抗生素相比，头孢吡肟与死亡率的统计学显著增加相关（风险比 1.26，95%置信区间 1.08-1.49）。美国 FDA 决定与药物赞助商合作重新评估荟萃分析数据。两年后，FDA 警报总结说，“数据并未表明头孢吡肟治疗患者的死亡率更高。头孢吡肟仍然是其批准适应症的适当治疗方法。”然而，对 FDA 报告的 52 页的全面评估仍表明安全性仍然是一个未解决的问题。FDA 和 Yahav 等人对这些发现进行的贝叶斯重新评估表明，头孢吡肟在中性粒细胞减少性发热患者中增加死亡率的可能性为 90.9%（通过 FDA 试验水平荟萃分析）、80.8%（通过 FDA 患者水平荟萃分析）和 99.2%（通过 Yahav 等人的荟萃分析），这转化为使用头孢吡肟导致额外死亡的需要伤害（NNH）的数量，即：FDA 试验水平荟萃分析，NNH = 109；FDA 患者水平荟萃分析，NNH = 76；Yahav 等人的荟萃分析，NNH = 54。在皮肤结构感染中观察到类似的有害概率，但在肺炎、腹腔内感染和尿路感染中则没有。总之，头孢吡肟应避免在中性粒细胞减少性发热或皮肤结构感染的患者中使用。
