Rationale:Acute eosinophilic pneumonia(AEP)is an acute pulmonary illness caused by eosinophilic infiltration of the lung parenchyma.It can happen after using drugs such as daptomycin and minocycline.AEP induced by imi...Rationale:Acute eosinophilic pneumonia(AEP)is an acute pulmonary illness caused by eosinophilic infiltration of the lung parenchyma.It can happen after using drugs such as daptomycin and minocycline.AEP induced by imipenem/cilastatin is a rare condition.Patient’s Concern:A 45-year-old male patient,who previously suffered from a urinary tract infection and treated with imipenem/cilastatin antibiotic,was presented to us with acute respiratory distress,soon after the initiation of the antibiotic.Computed tomography identified pulmonary infiltrates in the upper and middle lung fields and eosinophils were found to account for 36%of differential count of the broncho-alveolar lavage fluid.He also developed peripheral eosinophilia as the disease progressed.Diagnosis:AEP,secondary to imipenem/cilastatin therapy.Interventions:Steroid therapy was administered and imipenem/cilastatin antibiotic was discontinued.Outcomes:The patient improved completely following the therapy and had clear lung fields on follow-up.Lessons:Imipenem/cilastatin is an uncommon cause of AEP and requires close monitoring during therapy.展开更多
This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma co...This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma concentration-time curve(AUC)of cilastatin were significantly increased,while renal clearance and cumulative urinary excretion of cilastatin were decreased.At the same time,imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1(hOAT1)-HEK293 and human OAT3(hOAT3)-HEK293 cells.Probenecid,p-aminohippurate,and benzylpenicillin inhibited the uptake of imipenem and cilastatin in rat kidney slices and in hOAT1-and hOAT3-HEK 293 cells,respectively.The uptakes of imipenem and cilastatin in hOAT1-and hOAT3-HEK 293 cells were significantly higher than that in mock-HEK-293 cells.Moreover,the K m values of cilastatin were increased in the presence of imipenem with unchanged V max,indicating that imipenem inhibited the uptake of cilastatin in a competitive manner.When imipenem and cilastatin were co-administered,the level of imipenem was higher compared with imipenem alone both in vivo and in vitro.But,cilastatin significantly inhibited the uptake of imipenem when dehydropeptidase-1(DPEP1)was silenced by RNAi technology in hOAT1-and hOAT3-HEK 293 cells.In conclusion,imipenem and cilastatin are the substrates of OAT1 and OAT3.OAT1 and OAT3 mediate the DDI between imipenem and cilastatin.Meanwhile,cilastatin also reduces the hydrolysis of imipenem by inhibiting the uptake of imipenem mediated by OAT1 and OAT3 in the kidney as a complement.展开更多
目的应用蒙特卡罗模拟亚胺培南-西司他丁钠不同输注方法针对不同致病菌的最佳给药方案。方法回顾性分析某三甲医院2021年常见革兰阴性杆菌分布情况,按照2020年美国临床实验室标准化协会标准,对肺炎克雷伯菌、大肠埃希菌、铜绿假单胞菌...目的应用蒙特卡罗模拟亚胺培南-西司他丁钠不同输注方法针对不同致病菌的最佳给药方案。方法回顾性分析某三甲医院2021年常见革兰阴性杆菌分布情况,按照2020年美国临床实验室标准化协会标准,对肺炎克雷伯菌、大肠埃希菌、铜绿假单胞菌和鲍曼不动杆菌设定均匀分布的抑菌浓度(MIC)值,确定亚胺培南-西司他丁钠8种给药方案,运用PK/PD模型进行蒙特卡罗模拟10000例患者的目标获得概率(PTA),获得最佳给药方案。结果若MIC≤2μg·mL^(-1)时,除传统输注法0.5 g q8h与1 g q8h的给药方案PTA<90%,其余给药方案PTA均>90%;当MIC≥4μg·mL^(-1)时,采用持续输注的部分给药方式仍获得较好的抗菌效果(PTA>90%),而传统输注达不到理想的抗菌疗效(PTA<90%)。结论对亚胺培南-西司他丁钠敏感的革兰阴性杆菌,采用q6h的给药方案,传统输注与持续输注都能取得理想的治疗效果,而采用q8h的给药方案,持续输注法抗菌疗效效果佳效;对亚胺培南-西司他丁钠产生耐药的革兰阴性杆菌,需采用持续输注法才能获得理想的抗菌疗效。展开更多
文摘Rationale:Acute eosinophilic pneumonia(AEP)is an acute pulmonary illness caused by eosinophilic infiltration of the lung parenchyma.It can happen after using drugs such as daptomycin and minocycline.AEP induced by imipenem/cilastatin is a rare condition.Patient’s Concern:A 45-year-old male patient,who previously suffered from a urinary tract infection and treated with imipenem/cilastatin antibiotic,was presented to us with acute respiratory distress,soon after the initiation of the antibiotic.Computed tomography identified pulmonary infiltrates in the upper and middle lung fields and eosinophils were found to account for 36%of differential count of the broncho-alveolar lavage fluid.He also developed peripheral eosinophilia as the disease progressed.Diagnosis:AEP,secondary to imipenem/cilastatin therapy.Interventions:Steroid therapy was administered and imipenem/cilastatin antibiotic was discontinued.Outcomes:The patient improved completely following the therapy and had clear lung fields on follow-up.Lessons:Imipenem/cilastatin is an uncommon cause of AEP and requires close monitoring during therapy.
基金supported by a grant from the National Natural Science Foundation of China (No. 81874324,81473280,U1608283)the Natural Science Foundation of Liaoning (No. 20170540293)Dalian Science and technology innovation fund (No. 2018J12SN065).
文摘This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma concentration-time curve(AUC)of cilastatin were significantly increased,while renal clearance and cumulative urinary excretion of cilastatin were decreased.At the same time,imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1(hOAT1)-HEK293 and human OAT3(hOAT3)-HEK293 cells.Probenecid,p-aminohippurate,and benzylpenicillin inhibited the uptake of imipenem and cilastatin in rat kidney slices and in hOAT1-and hOAT3-HEK 293 cells,respectively.The uptakes of imipenem and cilastatin in hOAT1-and hOAT3-HEK 293 cells were significantly higher than that in mock-HEK-293 cells.Moreover,the K m values of cilastatin were increased in the presence of imipenem with unchanged V max,indicating that imipenem inhibited the uptake of cilastatin in a competitive manner.When imipenem and cilastatin were co-administered,the level of imipenem was higher compared with imipenem alone both in vivo and in vitro.But,cilastatin significantly inhibited the uptake of imipenem when dehydropeptidase-1(DPEP1)was silenced by RNAi technology in hOAT1-and hOAT3-HEK 293 cells.In conclusion,imipenem and cilastatin are the substrates of OAT1 and OAT3.OAT1 and OAT3 mediate the DDI between imipenem and cilastatin.Meanwhile,cilastatin also reduces the hydrolysis of imipenem by inhibiting the uptake of imipenem mediated by OAT1 and OAT3 in the kidney as a complement.
文摘目的应用蒙特卡罗模拟亚胺培南-西司他丁钠不同输注方法针对不同致病菌的最佳给药方案。方法回顾性分析某三甲医院2021年常见革兰阴性杆菌分布情况,按照2020年美国临床实验室标准化协会标准,对肺炎克雷伯菌、大肠埃希菌、铜绿假单胞菌和鲍曼不动杆菌设定均匀分布的抑菌浓度(MIC)值,确定亚胺培南-西司他丁钠8种给药方案,运用PK/PD模型进行蒙特卡罗模拟10000例患者的目标获得概率(PTA),获得最佳给药方案。结果若MIC≤2μg·mL^(-1)时,除传统输注法0.5 g q8h与1 g q8h的给药方案PTA<90%,其余给药方案PTA均>90%;当MIC≥4μg·mL^(-1)时,采用持续输注的部分给药方式仍获得较好的抗菌效果(PTA>90%),而传统输注达不到理想的抗菌疗效(PTA<90%)。结论对亚胺培南-西司他丁钠敏感的革兰阴性杆菌,采用q6h的给药方案,传统输注与持续输注都能取得理想的治疗效果,而采用q8h的给药方案,持续输注法抗菌疗效效果佳效;对亚胺培南-西司他丁钠产生耐药的革兰阴性杆菌,需采用持续输注法才能获得理想的抗菌疗效。
