Elting L S, Rubenstein E B, Kurtin D, Rolston K V, Fangtang J, Martin C G, Raad I I, Whimbey E E, Manzullo E, Bodey G P
Department of Internal Medicine Specialties, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Cancer. 1998 Dec 15;83(12):2597-607. doi: 10.1002/(sici)1097-0142(19981215)83:12<2597::aid-cncr27>3.0.co;2-l.
Discrepancies between the severity of toxicities reported in early clinical trials and recent clinical experience with vancomycin have led to confusion regarding the need for routine serum vancomycin level monitoring and discontinuation of vancomycin when toxicities occur. Therefore, the authors examined the incidence, outcomes, and predictive factors of vancomycin-associated toxicities in general oncology practice with the goal of developing clinically relevant prediction rules and guidelines.
All 742 consecutive cancer patients who received vancomycin at a comprehensive cancer center during a 3-month period were followed prospectively for the development and outcome of phlebitis, rash, ototoxicity, and nephrotoxicity. Logistic regression was used to derive a multiple variable model of the risk of nephrotoxicity. A clinical prediction rule, the Nephrotoxicity Risk Score, was developed from the risk model and validated prospectively.
Phlebitis occurred in 3% of patients (95% confidence interval [95% CI], 2-4%), predominantly those with recently inserted central venous catheters. Rashes occurred in 11% of patients (95% CI, 9-13%); however, all but 4 patients also were receiving beta-lactam antibiotics. Clinical evidence of ototoxicity developed in 6% of patients (95% CI, 4-9%) who were receiving vancomycin plus other ototoxic agents and only 3% of patients (95% CI, 2-5%) not receiving other ototoxic agents (P = 0.08). Nephrotoxicity occurred in 17% of patients (95% CI, 15-20%). Logistic regression revealed that factors associated with an increased risk of nephrotoxicity included administration of other mild to moderate (P = 0.01) or severely nephrotoxic agents (P < 0.001) or an acute physiology and chronic health evaluation (APACHE) score > 40 (P = 0.002). Elevated serum vancomycin peak levels did not reliably predict subsequent nephrotoxicity.
Vancomycin-associated toxicities usually are mild and self-limiting. Some patients are at a significantly higher risk of nephrotoxicity but the authors believe these individuals can be identified reliably with the Nephrotoxicity Risk Index using information available at vancomycin initiation. Further testing of the Nephrotoxicity Risk Index is ongoing.
早期临床试验报告的万古霉素毒性严重程度与近期临床经验之间存在差异，这导致了关于常规监测血清万古霉素水平以及在出现毒性时停用万古霉素必要性的困惑。因此，作者研究了普通肿瘤学实践中万古霉素相关毒性的发生率、结局及预测因素，目的是制定具有临床相关性的预测规则和指南。
对一家综合癌症中心在3个月期间连续接受万古霉素治疗的742例癌症患者，前瞻性地随访静脉炎、皮疹、耳毒性和肾毒性的发生情况及结局。采用逻辑回归分析得出肾毒性风险的多变量模型。根据该风险模型制定了一项临床预测规则——肾毒性风险评分，并进行前瞻性验证。
3%的患者发生静脉炎（95%置信区间[95%CI]，2% - 4%），主要是近期插入中心静脉导管的患者。11%的患者出现皮疹（95%CI，9% - 13%）；然而，除4例患者外，其余患者也同时接受β-内酰胺类抗生素治疗。接受万古霉素加其他耳毒性药物治疗的患者中，6%出现耳毒性临床证据（95%CI，4% - 9%），而未接受其他耳毒性药物治疗的患者中只有3%出现耳毒性临床证据（95%CI，2% - 5%）（P = 0.08）。17%的患者发生肾毒性（95%CI，15% - 20%）。逻辑回归分析显示，与肾毒性风险增加相关的因素包括使用其他轻度至中度（P = 0.01）或重度肾毒性药物（P < 0.001），或急性生理与慢性健康评估（APACHE）评分> 40（P = 0.002）。血清万古霉素峰值水平升高并不能可靠地预测随后的肾毒性。
万古霉素相关毒性通常较轻且为自限性。一些患者发生肾毒性的风险显著更高，但作者认为使用万古霉素开始治疗时可获得的信息，通过肾毒性风险指数能够可靠地识别这些个体。肾毒性风险指数的进一步验证正在进行中。
