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
目的评价碳青霉烯类抗生素美罗培南与亚胺培南/西司他汀在重症感染治疗中的疗效和安全性。方法利用计算机检索EMBASE、MEDLINE、Cochrane library和CNKI等数据库,纳入比较美罗培南与亚胺培南/西司他汀在相同给药剂量、给药方案下治疗重...目的评价碳青霉烯类抗生素美罗培南与亚胺培南/西司他汀在重症感染治疗中的疗效和安全性。方法利用计算机检索EMBASE、MEDLINE、Cochrane library和CNKI等数据库,纳入比较美罗培南与亚胺培南/西司他汀在相同给药剂量、给药方案下治疗重症感染疗效和安全性的随机对照试验(RCTs),采用Rev Man 5.2.6软件对入选试验进行Meta分析。结果共纳入16个随机对照试验,包括3055例重症感染患者。Meta分析结果显示,美罗培南相比亚胺培南/西司他汀在治疗重症感染中的临床有效率高[RR=1.03,95%CI(1.00,1.06)]。在临床治愈率[RR=1.04,95%CI(1.00,1.10)]与细菌清除率[RR=1.02,95%CI(0.97,1.07)]方面,美罗培南与亚胺培南/西司他汀相当。美罗培南组与药物相关不良反应发生率为11.6%,相比于亚胺培南/西司他汀组的13.6%[RR=0.85,95%CI(0.70,1.02)],但中枢神经系统不良反应在亚胺培南/西司他汀组发生率较高(P<0.01)。结论现有证据表明,美罗培南在重症感染治疗中的临床有效率略优于亚胺培南/西司他汀,中枢神经系统不良反应发生率显著低于亚胺培南/西司他汀。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.
文摘目的评价碳青霉烯类抗生素美罗培南与亚胺培南/西司他汀在重症感染治疗中的疗效和安全性。方法利用计算机检索EMBASE、MEDLINE、Cochrane library和CNKI等数据库,纳入比较美罗培南与亚胺培南/西司他汀在相同给药剂量、给药方案下治疗重症感染疗效和安全性的随机对照试验(RCTs),采用Rev Man 5.2.6软件对入选试验进行Meta分析。结果共纳入16个随机对照试验,包括3055例重症感染患者。Meta分析结果显示,美罗培南相比亚胺培南/西司他汀在治疗重症感染中的临床有效率高[RR=1.03,95%CI(1.00,1.06)]。在临床治愈率[RR=1.04,95%CI(1.00,1.10)]与细菌清除率[RR=1.02,95%CI(0.97,1.07)]方面,美罗培南与亚胺培南/西司他汀相当。美罗培南组与药物相关不良反应发生率为11.6%,相比于亚胺培南/西司他汀组的13.6%[RR=0.85,95%CI(0.70,1.02)],但中枢神经系统不良反应在亚胺培南/西司他汀组发生率较高(P<0.01)。结论现有证据表明,美罗培南在重症感染治疗中的临床有效率略优于亚胺培南/西司他汀,中枢神经系统不良反应发生率显著低于亚胺培南/西司他汀。
