替加环素治疗多耐药重症胰腺炎相关腹腔感染的临床效果及有效血药浓度控制

Clinical effect and effective blood concentration control of tigecycline in the treatment of multidrug resistant severe acute pancreatitis associated abdominal infection

目的应用替加环素对多耐药重症胰腺炎(SAP)相关腹腔感染患者进行抗多药耐药菌(MDRB)治疗,分析其临床效果及有效血药浓度,旨在为临床治疗多耐药SAP相关腹腔感染提供依据。方法选取2015-01-01-2019-12-31平顶山市中医医院收治的53例多耐药重症胰腺炎相关腹腔感染患者为研究对象,应用替加环素进行抗菌治疗。检测患者治疗前后炎症指标(WBC、CRP、PCT、IL-6)和免疫功能指标(IgA、IgG、IgM)水平,观察临床疗效和病原菌学疗效。采用高效液相色谱法检测替加环素血药浓度(峰浓度、中浓度、谷浓度),计算曲线下面积(AUC_(0-24h)),并分析AUC_(0-24h)值与患者炎症指标、免疫功能指标的相关性。结果53例SAP相关性腹腔感染患者标本中共分离出94株病原菌,其中49株为多药耐药菌。应用替加环素抗菌治疗2周后,临床有效率为73.58%(39/53),病原菌清除率为84.91%(45/53)。有效患者和无效患者峰浓度分别为(1.46±0.17)和(1.27±0.14)mg/L,t=2.649,P=0.014;中浓度分别为(0.81±0.13)和(0.67±0.11)mg/L,t=2.540,P=0.018;谷浓度分别为(0.54±0.11)和(0.42±0.09)mg/L,t=2.589,P=0.016;MIC分别为(1.26±0.47)和(4.48±1.69)mg/L,t=-7.937,P<0.001;2组AUC_(0-24h)分别为(20.74±2.61)和(17.03±2.77)mg·h/L,t=3.183,P=0.004。ROC分析结果显示,患者AUC_(0-24h)水平评估替加环素临床疗效的AUC为0.917,当Cut-off值为21.46 mg·h/L时,灵敏度和特异性分别为0.908和0.896。应用替加环素抗菌治疗2周后,AUC_(0-24h)≥21.46 mg·h/L组与AUC_(0-24h)<21.46 mg·h/L组患者WBC分别为(3.42±1.19)×10^(9)L^(-1)和(14.07±4.36)×10^(9)L^(-1),t=13.742,P<0.001;CRP分别为(10.25±2.89)和(44.36±9.23)mg/L,t=20.345,P<0.001;PCT分别为(0.35±0.11)和(3.28±1.24)g/L,t=14.214,P<0.001;IL-6分别为(10.34±2.67)和(37.29±10.28)U/L,t=14.847,P<0.001;IgA分别为(1.59±0.18)和(2.27±0.26)g/L,t=11.086,P<0.001;IgG分别为(1.21±0.21)和(0.95±0.27)g/L,t=-3.833,P<0.001;IgM分别为(11.48±2.71)和(16.47±3.43)g/L,t=-5.264,P<0.001。结论替加环素治疗多耐药重症胰腺炎相关腹腔感染,安全有效,应用过程中AUC_(0-24h)的目标值需要达到21.46 mg·h/L,才能够得到较佳的治疗效果。

Objective The tigecycline was used for anti multidrug resistant bacteria(MDRB)treatment in patients with evere acute pancreatitis(SAP)-related abdominal infection,and its clinical effect and effective blood concentration were analyzed,so as to provide basis for clinical treatment of multidrug-resistant SAP-related abdominal infection.Methods A total of 53 patients with multidrug-resistant SAP-related abdominal infection were selected,who admitted to Pingdingshan Hospital of Traditional Chinese Medicine from January 1,2015 to December 31,2019 and treated with tigecycline.Levels of inflammatory indexes(WBC,CRP,PCT,IL-6)and immune function indicators(IgA,IgG,IgM)before and after treatment were detected,and the clinical efficacy and pathogenic efficacy were observed.The blood concentration of tigecycline(peak concentration,medium concentration,and trough concentration)was determined by HPLC,and the area under the curve(AUC_(0-24h))was calculated,and the correlation between AUC_(0-24h)value and inflammatory index and immune function index was analyzed.Results A total of 94 strains of pathogens were isolated from 53 patients with SAP-related abdominal infection,49 of which were MDRB.After two weeks of anti-bacterial treatment with tigecycline,the clinical effective rate was 73.58%(39/53),and the pathogen clearance rate was 84.91%(45/53).The peak concentrations of effective patients and ineffective patients were(1.46±0.17)and(1.27±0.14)mg/L,t=2.649,P=0.014,respectively.The medium concentrations were(0.81±0.13)and(0.67±0.11)mg/L,t=2.540,P=0.018.The valley concentrations were(0.54±0.11)and(0.42±0.09)mg/L,t=2.589,P=0.016.The MIC were(1.26±0.47)and(4.48±1.69)mg/L,t=-7.937,P<0.001.AUC_(0-24h)in the two groups were(20.74±2.61)and(17.03±2.77)mg·h/L,t=3.183,P=0.004.ROC analysis showed that the AUC for evaluating the clinical efficacy of tegacyclin at AUC_(0-24h)level was 0.917.When the Cut-off value was 21.46mg·h/L,the sensitivity and specificity were 0.908and 0.896,respectively.After 2weeks of antibacterial treatment with tegacyclin,the WBC of patients in AUC_(0-24h)≥21.46mg·h/L group and AUC_(0-24h)<21.46mg·h/L group were(3.42±1.19)×10^(9)L^(-1)and(14.07±4.36)×10^(9)L^(-1),respectively,t=13.742,P<0.001.CRP were(10.25±2.89)and(44.36±9.23)mg/L,t=20.345,P<0.001.PCT were(0.35±0.11)and(3.28±1.24)g/L,t=14.214,P<0.001.IL-6were(10.34±2.67)and(37.29±10.28)U/L,t=14.847,P<0.001.IgA were(1.59±0.18)and(2.27±0.26)g/L,t=11.086,P<0.001.IgG were(1.21±0.21)and(0.95±0.27)g/L,t=-3.833,P<0.001.IgM were(11.48±2.71)and(16.47±3.43)g/L,t=-5.264,P<0.001.Conclusions Tigecycline is safe and effective in the treatment of multi-drug resistant pancreatitis-associated abdominal infections.The target value of AUC_(0-24h)needs to reach 21.46mg·h/L to get better therapeutic effect.