肾功能不全与肾功能正常患者应用利奈唑胺致血小板减少发生情况分析

目的探讨应用利奈唑胺患者的肾功能对该药所致血小板减少的影响,为肾功能不全患者安全使用利奈唑胺提供依据。方法收集2008年1月至2011年5月因革兰阳性菌致肺部感染在空军总医院住院、单独或联合应用利奈唑胺治疗的肾功能不全、肾功能正常患者的临床资料进行回顾性分析,主要观察指标为用药前后血小板计数和血清肌酐、尿素氮水平。为排除联合用药的影响,按照年龄、住院时间匹配原则,选择同期因感染住院且肾功能正常、未使用利奈唑胺但使用利奈唑胺联合疗法中的另外1种抗菌药物的患者,作为单独应用该种抗菌药物的对照。结果应用利奈唑胺患者共43例,其中肾功能不全患者(肾功能不全组,22例)男15例,女7例,年龄38～93(74.8±14.2)岁,16例联用利奈唑胺和其他抗菌药物,包括替考拉宁(1例)、美罗培南(4例)、万古霉素(1例)、甲硝唑(1例)、亚胺培南西司他丁钠(6例)和头孢哌酮舒巴坦(3例);肾功能正常患者(肾功能正常组,21例)男17例、女4例,年龄38～90(73.8±13.7)岁。替考拉宁、美罗培南、万古霉素、甲硝唑、亚胺培南西司他丁钠和头孢哌酮舒巴坦组各22例。应用利奈唑胺的时间:肾功能不全组为1～13(5.4±3.6)d,肾功能正常组为2～13(5.9±3.0)d。肾功能不全组应用利奈唑胺前后血小板计数分别为(207±94)×109/L和(131±97)×109/L,差异有统计学意义(P<0.01)。肾功能正常组患者应用利奈唑胺前后小板计数分别为(208±89)×109/L和(181±94)×109/L,差异无统计学意义(P>0.05)。肾功能不全组与肾功能正常组血小板减少发生率分别为59.1%(13/22)与28.6%(6/21),差异有统计学意义(P<0.05)。2组出现血小板减少的患者均无出血症状,停药3～10(5.7±3.3)d后均逐渐恢复至基线水平。肾功能不全组中联用甲硝唑、万古霉素、替考拉宁者各1例,均出现血小板减少;联用美罗培南者4例,3例出现血小板减少;联用头孢哌酮舒巴坦者3例,2例出现血小板减少;联用亚胺培南西司他汀钠者6例,3例出现血小板减少。而替考拉宁、美罗培南、万古霉素、甲硝唑、亚胺培南西司他丁钠和头孢哌酮舒巴坦组患者用药前后血小板计数差异均无统计学意义(均P>0.05),仅有头孢哌酮舒巴坦组的1例患者出现血小板减少(轻度)。肾功能不全组患者联用利奈唑胺和上述6种抗菌药物之一时血小板减少发生率与单独使用其中1种抗菌药物的各组患者比较,差异均有统计学意义(均P<0.05)。结论患者肾功能对利奈唑胺所致血小板减少发生率有一定影响。肾功能不全患者应用利奈唑胺期间应定期监测血小板计数,一旦出现血小板减少应立即停药。

Analysis of occurrence of linezolid induced thrombocytopenia in patients with renal insufficiency and normal renal function

Objective To explore the effects of renal function on linezolid-induced thrombocytopenia in patients who receiving the drug in order to provide evidence for safe use of linezolid in patients with renal insufficiency.Methods The clinical data of patients with renal insufficiency or normal renal function and pulmonary infection cansed by Gram positive bacteria,who were treated with linezolid alone or combined with other drugs,and hospitalized in the Air-Force General Hospital during the period from January 2008 to May 2011,were collected and analyzed retrospectively.The main observational indices such as platelet count,serum creatinine and urea nitrogen levels were measured before and after drug application.According to the principle of proprer matching in age and duration of hospitalization,some infection patients with normal renal function,who were hospitalized during the same time period and treated without linezolid,but with a antibacterial drug of the combined linezolid therapy,were selected as controls in order to exclude the influence due to drug combination.Results A total of 43 patients received linezolid,the patients with renal insufficiency(the renal insufficiency group,22 cases) comprised 15 male and 7 female aged 38-93(74.8±14.2) years,16 patients were treated with combined use of linezolid and other kinds of antibacterial agents,including teicoplanin(1 case),meropenem(4 cases),vancomycin(1 case),metronidazole(1 case),imipenem(6 cases),and cefoperazone/sulbactam(3 cases).The patients with normal renal function(normal renal function group,21 cases) included 17 male and 4 females aged 38-90(73.8±13.7) years.The patient’ s number in each group of teicoplanin,meropenem,vancomycin,metronidazole,imipenem and cefoperazone/sulbactam was 22 cases.The duration of linezolid therapy was 1-13(5.4±3.6) days in the renal insufficiency group,and 2-13(5.9±3.0) days in the normal renal function group.The platelet count in the renal insufficiency group before and after receiving linezolid were(207±94)×109/L and(131±97)×109/L,respectively.The difference was statistically significance(P<0.01).The platelet count in the normal renal function group before and after receiving linezolid was(208±89)×109/L and(181±94)×109/L,respectively(P>0.05).The incidence of thrombocytopenia in the renal insufficiency and normal renal function groups was 59.1%(13/22) and 28.6%(6/21),respectively.The difference was statistically significant(P<0.05).There were no symptoms of hemorrhage in patients with thrombocytopenia in the 2 groups.The platelet count gradually returned to baseline 3-10(5.7±3.3) days after drug withdraw.The patients in the renal insufficiency group,who received combination therapy with metronidazole(1 case),vancomycin(1 case),and teicoplanin(1 case) developed thrombocytopenia.Three cases developed thrombocytopenia in 4 patients who were treated with combined use of linezolid and meropenem;2 cases developed thrombocytopenia in 3 patients who were treated with combined use of linezolid and cefoperazone/sulbactam;3 of 6 patients who were treated with combined use of linezolid and imipenem developed thrombocytopenia.There were no statistically significance in platelet count before and after medication among teicoplanin,meropenem,vancomycin,metronidazole,imipenem,and cefoperazone/sulbactam groups(P>0.05 for all comparisons).Only one patient developed thrombocytopenia(mild) in the cefoperazone/sulbactam group.The differences in incidence of thrombocytopenia between the patients who were treated with combined use of linezolid and one of the 6 antibacterial agents mentioned above in the renal insufficiency group and the patients who received one of 6 antibacterial agents alone in the other groups were statistically significance(P<0.05 for all comparisons).Conclusion The patient’ s renal function may affect the incidence of linezolid-induced thrombocytopenia.The platelet count in patient with renal insufficiency should be monitored regularly when receiving linezolid.If thrombocytopenia occurs,the drug should be discontinued immediately.