万古霉素单药与联合β-内酰胺类药物对脓毒症患者急性肾损伤发生和预后的影响

The effects of vancomycin monotherapy and combined beta-lactam therapy on occurrence and prognosis of acute kidney injury in patients with sepsis

目的探讨万古霉素(VAN)单药治疗与VAN联合哌拉西林-他唑巴坦(TZP)或美罗培南(MEM)的抗生素方案对脓毒症患者急性肾损伤(AKI)发生、持续时间、恢复情况及临床预后的影响。方法研究纳入接受VAN、TZP或MEM治疗并维持至少48 h的脓毒症患者338例,其中78例患者接受VAN单药治疗(VAN组),175例患者接受VAN+TZP治疗(VAN+TZP组),余85例患者接受VAN+MEM治疗(VAN+MEM组)。比较3组患者临床资料、AKI发生情况和临床结果。采用Kaplan-Meier分析和Log-rank检验比较3组患者AKI发生概率。采用多因素Logistic回归模型分析AKI发生的独立危险因素。结果VAN+TZP组与VAN+MEM组患者的急性生理与慢性健康评估Ⅱ(APACHEⅡ)评分、去甲肾上腺素使用比例明显高于VAN组。VAN+TZP组肾上腺素、多巴胺使用比例明显高于VAN组与VAN+MEM组。与VAN组和VAN+TZP组比较,VAN+MEM组患者的两性霉素与氨基糖苷类使用比例最高,而血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂(ACEI/ARB)使用比例最低(P<0.05)。3组患者VAN剂量及抗生素疗程差异无统计学意义。VAN+TZP组患者AKI发生率明显高于VAN组与VAN+MEM组(50.3%vs.23.1%vs.25.9%,P<0.01),而后2组患者AKI发生率差异无统计学意义(P>0.0167)。VAN+TZP组患者AKI 2级比例明显高于VAN组与VAN+MEM组(21.7%vs.7.7%vs.9.4%,P<0.01)。3组患者30 d内透析需求、AKI恢复率、AKI恢复时血肌酐(SCr)、AKI持续时间、住院天数与30 d病死率差异无统计学意义(P>0.05)。Kaplan-Meier分析显示,VAN+TZP组患者AKI的累积发生风险明显高于VAN组和VAN+MEM组患者(log-rankχ^2=14.491,P=0.001)。多因素Logistic回归模型分析结果显示,APACHEⅡ评分增加(OR=1.041,95%CI:1.008~1.075,P=0.013)、使用去甲肾上腺素(OR=2.200,95%CI:1.254~3.860,P=0.006)和VAN+TZP联合治疗(OR=2.064,95%CI:1.104~3.856,P=0.023)是影响AKI发生的独立危险因素。结论VAN+TZP联合治疗的脓毒症患者AKI发生率高于VAN单药和VAN+MEM联合治疗,但对最终临床结果没有决定性的影响。

Objective To explore the effects of vancomycin(VAN)monotherapy and combination of VAN+piperacillin-tazobactam(TZP)or meropenem(MEM)on the incidence,duration,recovery and clinical prognosis of acute kidney injury(AKI).Methods A total of 338 sepsis patients admitted to the emergency department of the Second Affiliated Hospital of Hainan Medical College from January 2018 to May 2020 and were given VAN,TZP or MEM and maintained for at least 48 h were enrolled.Of these patients,78 patients received VAN monotherapy(group VAN),175 patients received combination therapy with VAN+TZP(group VAN+TZP),and 85 patients received combination therapy with VAN+MEM(group VAN+MEM).The clinical data,incidence of AKI and clinical outcomes were compared between the three groups.Kaplan-Meier analysis and Log-rank test were performed to compare AKI developmental probability in the three groups.The independent risk factors of AKI were analyzed by multivariate Logistic regression model.Results The acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,and the proportion of norepinephrine use were significantly higher in group VAN+TZP and group VAN+MEM than those in group VAN.The proportion of adrenalin and dopamine use was significantly higher in group VAN+TZP than that in group VAN and group VAN+MEM.Compared with group VAN and group VAN+TZP,patients in group VAN+MEM had the highest proportion of amphotericin and aminoglycoside use,while the proportion of angiotensin converting enzyme inhibitors or angiotensin receptor blockers(ACEI/ARB)use was the lowest(P<0.05).There were no significant differences in the duration of antibiotic therapy and mean VAN daily dose between the three groups.The incidence of AKI was significantly higher in group VAN+TZP than that in group VAN and VAN+MEM(50.3%vs.23.1%vs.25.9%,P<0.001),while there was no significant difference between group VAN and group VAN+MEM(P>0.0167).The proportion of AKI stage 2 in group VAN+TZP was significantly higher than that in group VAN and group VAN+MEM(21.7%vs.7.7%vs.9.4%,P<0.01).There were no significant differences in the dialysis within 30 days,the recovery rate of AKI,serum creatinine(SCr)at AKI recovery,duration of AKI,length of hospital stay and 30-day mortality between the three groups(P>0.05).The Kaplan-Meier analysis showed that the cumulative risk of AKI was significantly higher in group VAN+TZP than that in group VAN and group VAN+MEM(log-rankχ^2=14.491,P=0.001).Multivariate Logistic regression model analysis showed that the APACHEⅡ scores(OR=1.041,95%CI:1.008-1.075,P=0.013),the use of norepinephrine(OR=2.200,95%CI:1.254-3.860,P=0.006)and the combination therapy of VAN+TZP(OR=2.064,95%CI:1.104-3.856,P=0.023)were independent risk factors for AKI.Conclusion The AKI incidence in sepsis patients treated with VAN+TZP is higher than those treated with VAN monotherapy and VAN+MEM.However,this does not have a decisive influence on final clinical outcomes.