1.Clinical efficacy of sulbactam-durlobactam in treating patients with carbapenem-resistant Acinetobacter baumannii pulmonary infection and drug concentration surveillance
Yue CHEN ; Lin QIAO ; Zhongyao XIE ; Wenqian CHEN ; Dongjie GUO ; Pengmei LI
Chinese Journal of Nosocomiology 2025;35(20):3105-3109
OBJECTIVE To evaluate the efficacy of sulbactam-durlobactam combined with meropenem in treating carbapenem-resistant Acinetobacter baumannii(CRAB)pulmonary infection.METHODS A total of 16 patients treated at China-Japan Friendship Hospital from Jan.1,2025 to Jun.1,2025 were included.Retrospective analy-sis was conducted on patients'basic situation,preliminary treatment regimens,infection-related diagnoses,etiolo-gy and clinical outcomes.Therapeutic drug monitoring(TDM)for sulbactam was also performed.RESULTS By the end of the treatment course,13 patients achieved etiological eradication of CRAB and clinical improvement,while 1 patient experienced CRAB recurrence within one month.Three patients showed treatment failure.TDM for sulbactam was performed in 13 patients.Except for one slightly lower,all achieved trough plasma concentra-tions above the minimum inhibitory concentration(MIC)(100%T>MIC,MIC=4 mg/L based on clinical breakpoints).Dosage adjustments based on plasma concentrations were made for 4 patients,with 3 receiving re-duced doses and 1 receiving an increased dose.CONCLUSIONS Sulbactam-durlobactam combined with meropenem demonstrates superior efficacy in treating CRAB compared to other regimens.Under the recommended dosage,all patients can achieve the PK/PD target for sulbactam.
2.Clinical efficacy of sulbactam-durlobactam in treating patients with carbapenem-resistant Acinetobacter baumannii pulmonary infection and drug concentration surveillance
Yue CHEN ; Lin QIAO ; Zhongyao XIE ; Wenqian CHEN ; Dongjie GUO ; Pengmei LI
Chinese Journal of Nosocomiology 2025;35(20):3105-3109
OBJECTIVE To evaluate the efficacy of sulbactam-durlobactam combined with meropenem in treating carbapenem-resistant Acinetobacter baumannii(CRAB)pulmonary infection.METHODS A total of 16 patients treated at China-Japan Friendship Hospital from Jan.1,2025 to Jun.1,2025 were included.Retrospective analy-sis was conducted on patients'basic situation,preliminary treatment regimens,infection-related diagnoses,etiolo-gy and clinical outcomes.Therapeutic drug monitoring(TDM)for sulbactam was also performed.RESULTS By the end of the treatment course,13 patients achieved etiological eradication of CRAB and clinical improvement,while 1 patient experienced CRAB recurrence within one month.Three patients showed treatment failure.TDM for sulbactam was performed in 13 patients.Except for one slightly lower,all achieved trough plasma concentra-tions above the minimum inhibitory concentration(MIC)(100%T>MIC,MIC=4 mg/L based on clinical breakpoints).Dosage adjustments based on plasma concentrations were made for 4 patients,with 3 receiving re-duced doses and 1 receiving an increased dose.CONCLUSIONS Sulbactam-durlobactam combined with meropenem demonstrates superior efficacy in treating CRAB compared to other regimens.Under the recommended dosage,all patients can achieve the PK/PD target for sulbactam.
3.Liver injury caused by the combination of voriconazole and nirmatrelvir/ritonavir
Adverse Drug Reactions Journal 2024;26(2):123-125
A 66-year-old male patient who underwent lung transplantation took a combination therapy with tacrolimus, mycophenolate sodium, and prednisone for a long time to resist rejection.Due to the occurrence of novel coronavirus and pulmonary fungal infection,the patient was given antiviral therapy with nirmatrelvir/ritonavir (Pavlovid), followed by antifungal therapy with voriconazole 2 days later. Before voriconazole treatment, the patient′s alanine aminotransferase was 34 U/L, and aspartate aminotransferase was 28 U/L. On the 4th day of the combination of voriconazole and Paxlovid, the patient′s blood trough concentration of voriconazole was 16.06 mg/L, alanine aminotransferase was 176 U/L, and aspartate amino- transferase was 166 U/L. Voriconazole was discontinued immediately and 2 days later,Paxlovid was discontinued. Five days after discontinuation of voriconazole, the patient′s liver function returned to normal; 9 days later, blood trough concentration of voriconazole was 5.84 mg/L. It was considered that the patient′s liver injury was caused by the combination of voriconazole and Paxlovid.
4.Liver injury caused by the combination of voriconazole and nirmatrelvir/ritonavir
Adverse Drug Reactions Journal 2024;26(2):123-125
A 66-year-old male patient who underwent lung transplantation took a combination therapy with tacrolimus, mycophenolate sodium, and prednisone for a long time to resist rejection.Due to the occurrence of novel coronavirus and pulmonary fungal infection,the patient was given antiviral therapy with nirmatrelvir/ritonavir (Pavlovid), followed by antifungal therapy with voriconazole 2 days later. Before voriconazole treatment, the patient′s alanine aminotransferase was 34 U/L, and aspartate aminotransferase was 28 U/L. On the 4th day of the combination of voriconazole and Paxlovid, the patient′s blood trough concentration of voriconazole was 16.06 mg/L, alanine aminotransferase was 176 U/L, and aspartate amino- transferase was 166 U/L. Voriconazole was discontinued immediately and 2 days later,Paxlovid was discontinued. Five days after discontinuation of voriconazole, the patient′s liver function returned to normal; 9 days later, blood trough concentration of voriconazole was 5.84 mg/L. It was considered that the patient′s liver injury was caused by the combination of voriconazole and Paxlovid.
5.A real-world survey of the effect of voriconazole on tacrolimus blood concentration after lung transplantation
Dongjie GUO ; Pengmei LI ; Wenqian CHEN ; Lihong LIU
China Pharmacy 2023;34(20):2519-2524
OBJECTIVE To provide a reference for the dose adjustment of tacrolimus in patients who underwent lung transplantation after combined use of voriconazole. METHODS The clinical data of lung transplantation patients who used voriconazole and tacrolimus in our hospital from January 2020 to December 2022 were collected retrospectively. The effects of voriconazole on the valley concentration, daily dose and standardized blood concentration of tacrolimus were analyzed by using SPSS 21.0 software; multiple linear regression analysis was conducted for the factors that may affect the standardized blood concentration of tacrolimus. RESULTS A total of 153 lung transplantation patients were included. After the combination of voriconazole, the average daily dose of tacrolimus decreased from 3.37 mg to 0.76 mg, and valley concentration and standardized blood concentration were increased significantly (P<0.000 1). The average daily dose of voriconazole was negatively correlated with the standardized blood drug concentration of tacrolimus (P=0.000 1,r=-0.224). The valley concentration of voriconazole was positively correlated with valley concentration (P<0.000 1,r=0.316) and standardized blood concentration (P<0.000 1,r= 0.249) of tacrolimus. After combination with voriconazole, the standardized blood drug concentration of patients who underwent single lung transplantation was significantly higher than those who underwent double lung transplantation, and the standardized blood concentration of tacrolimus after oral administration of voriconazole was significantly higher than after intravenous drip of voriconazole (P<0.05). Most liver and kidney function indicators showed no significant changes. The results of multiple factor regression analysis showed that the valley concentration of voriconazole had a significant impact on the standardized blood concentration of tacrolimus (P<0.001). CONCLUSIONS The valley concentration of voriconazole has greatest influence on the blood concentration and dose adjustment of tacrolimus, which is an independent influencing factor. In clinical practice, the dose of tacrolimus should be reduced in combination with voriconazole, and therapeutic drug monitoring should be conducted for both drugs.
6.Vasorelaxant effect and mechanism of niclosamide ethanolamine on rat coronary artery
Qiying SONG ; Pengmei GUO ; Lina DONG ; Miaomiao DONG ; Yu LIU
Chinese Journal of Comparative Medicine 2018;28(5):65-69
Objective To investigate the vasorelaxant effect and possible mechanism of niclosamide ethanolamine (NEN)on isolated rat coronary artery(RCA). Methods Wire myograph was used to record myogenic tone of vessels. The vasorelaxant effect of NEN was studied in RCA precontracted with either KCl or U46619. Study of related inhibitors was performed to investigate possible involvement of potassium channels and the mitogen-activated protein kinase(MAPK) signaling pathway in vasorelaxation. The effect of NEN on Ca2+mobilization was determined by observing vasoconstrictor-induced contractions in tissue solution deprived of Ca2+followed by Ca2+restoration. Results NEN(0.5-3.0 μmol/L) relaxed RCA precontracted with KCl or U46619 in a concentration-dependent manner. MAPK inhibitors(PD98059 and SB239063)reduced the relaxant effect of NEN,while the potassium-channel blockers(tetraethylamine,4-aminopyridine, BaCl2,and glibenclamide)did not significantly affect relaxation. NEN specifically inhibited the contraction component dependent on extracellular Ca2+influx in vessels stimulated with KCl and U46619, with a negligible effect on the component dependent on intracellular Ca2+release. Conclusions NEN exhibits vasodilator properties in RCA. Inhibition of extracellular Ca2+influx and activation of the MAPK signaling pathway may be involved in NEN-induced RCA vasorelaxation.
7.Mechanisms underlying contraction of rat isolated coronary artery induced by acidosis
Zefang HE ; Xiaomin HOU ; Rong YANG ; Fangwen FAN ; Pengmei GUO ; Yu LIU ; Mingsheng ZHANG
Chinese Journal of Pathophysiology 2017;33(5):838-842
AIM:To explore the mechanisms underlying contraction induced by extracelluar acidosis (pHex6.8) in rat isolated coronary artery (RCA).METHODS:Using the microvessel tension recorder system, the effects of acid-base transporters on RCA contraction induced by pHex6.8 were explored by applying the selective pharmacological inhibitors of Na+-H+ exchanger 1 (NHE-1) and Na+-HCO-3 cotransporter (NBC), HOE-642 and S0859, respectively.The effects of chloride channel on RCA contraction induced by pHex6.8 were explored by applying the inhibitors of chloride channel (NPPB and NFA), and by replacing the extracellular NaCl with equimolar NaBr.RESULTS:pHex6.8 augmented the resting tension of RCA, and the maximum contraction was (3.90±0.95) mN.HOE-642 at 30 μmol/L and S0859 at 100 μmol/L both inhibited the contraction of RCA induced by pHex6.8 (P<0.01).NPPB and NFA both inhibited the contraction of RCA induced by pHex6.8 or KCl (60 mmol/L) in a concentration-dependent manner.NPPB and NFA (100 μmol/L) both inhibited the contraction of RCA induced by U46619 (1 μmol/L).Replacing the extracellular NaCl with equimolar NaBr almost completely inhibited RCA contraction induced by pHex6.8 (P<0.01), but had no obvious effect on the contraction induced by KCl (60 mmol/L) or U46619 (1 μmol/L).CONCLUSION:Extracellular acidosis-induced contraction in RCA may be related to the activated NHE-1 and NBC, and it may be also related to the enhanced chloride transport across the membrane.
8.Cross-sectional Survey on Therapeutic Drug Monitoring of Vancomycin in Our Hospital
Dongjie GUO ; Pengmei LIN ; Wenwen DU ; Gang CUI ; Wenqian CHEN ; Xianglin ZHANG
China Pharmacy 2016;27(24):3320-3323
OBJECTIVE:To explore the necessity of developing therapeutic drug monitoring of vancomycin in our hospital and its existing problems,and provide a reasonable basis for the clinical rational use of vancomycin. METHODS:The cross-sectional survey was designed to collect the clinical data of 92 patients with therapeutic drug monitoring of vancomycin and statistically ana-lyze 192 cases of plasma concentration monitoring data. RESULTS:The average plasma trough concentration was (15.96 ± 8.06) mg/L;with the increase of age,the plasma trough concentration was increasing,there was no significant difference in the plasma trough concentration among different age groups (P=0.000);there were only 13 cases (6.77%) that obtained the plasma trough concentration within 30 min before the fourth dose;after using wancomycin,clearance rates of Cr and the endogenous creatinine were slightly higher than before,but there was no significant difference(P=0.722);36 cases(39.13%)showed vancomycin sus-ceptible gram positive cocci;after using wancomycin,the body temperature,white blood cell count and neutrophil percentage were lower than before,the differences were statistically significant (P=0.006,P=0.000,P=0.000);48 cases (52.17%) in treatment received initial loading dose,and only 15 cases (16.30%) did not use in combination with other anti infective drugs. CONCLU-SIONS:The results showed there are still a lot of problems in the treatment of vancomycin in our hospital,for example,the stan-dard rate of the plasma trough concentration is about 50%;most of the time of blood sampling is not reasonable;the detection rate of the pathogen is low;only about half of the cases are given the loading dose,etc. Therefore clinical pharmacists’intervention for blood sampling is an important part to promote rational drug therapy monitoring. Meanwhile,data interpretation of the monitoring results of serum drug concentration of vancomycin is a basic method for clinical pharmacists in clinical monitoring to correct the un-reasonable operations,and also the necessary measures for preventing the drug renal toxicity,it is a very important significance for the medication safety and effectiveness especially in severe infection patients,the elderly,the children and the people with renal function insufficiency.

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