Castor is one of the top 10 oil crops in the world and has extremely valuable uses.Castor inflorescences directly affect yield,so the study of inflorescence development is very important in increasing castor yield.Our...Castor is one of the top 10 oil crops in the world and has extremely valuable uses.Castor inflorescences directly affect yield,so the study of inflorescence development is very important in increasing castor yield.Our previous studies have shown that the PIP5K gene family(PIP5Ks)is associated with inflorescence development.In this study,to determine the function of each PIP5K gene in castor,a female Lm-type castor line,aLmAB2,was used to determine the relative expression levels of the PIP5Ks in castor inflorescences.Six PIP5K genes were heterologously overexpressed in Arabidopsis thaliana,the relative expression of each gene and the effect on plants was determined in A.thaliana,and the relationships among the PIP5Ks in castor were inferred.The expression levels of the PIP5Ks in the female Lm-type castor line aLmAB2 were analyzed.The relative expression levels of the PIP5K9 and PIP5K11 genes were high(p<0.05)in isofemale inflorescences,and those of PIP5K1,PIP5K2,PIP5K6,and PIP5K8 were high(p<0.05)in female inflorescences but low(p<0.05)in bisexual inflorescences.The PIP5Ks were heterologously overexpressed in A.thaliana,and T3-generation plants with stable genetic resistance,i.e.,AT-PIP5K^(+)plants(AT-PIP5K1^(+),AT-PIP5K2^(+),AT-PIP5K6^(+),AT-PIP5K8^(+),AT-PIP5K9^(+),and ATPIP5K11^(+) plants),were obtained.Biological tests of the AT-PIP5K+plants showed that the growth of the main stem was significantly delayed in AT-PIP5K+plants compared with Columbia wild-type(WT)A.thaliana plants;the PIP5K1 and PIP5K2 genes promoted lateral stem growth and flower and silique development;and the PIP5K6,PIP5K8,PIP5K9 and PIP5K11 genes inhibited lateral stem growth and flower and silique development.The correlations among PIP5Ks in castor suggest that there may be a synergistic relationship among PIP5K1,PIP5K2,and PIP5K6 in castor inflorescences,and PIP5K8,PIP5K9,and PIP5K11 are complementary to the other three genes.展开更多
AIM：To analyze the in vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens isolated from patients with acute cholangitis. METHODS： In this prospective study a total of 65 patients with acute c...AIM：To analyze the in vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens isolated from patients with acute cholangitis. METHODS： In this prospective study a total of 65 patients with acute cholangitis due to biliary stone obstruction （n = 7）, benign biliary stricture （n = 16）, and malignant biliary stricture （n = 42） were investigated with regard to spectrum of bacterial infection and antibiotic resistance. Pathogens were isolated from bile cultures in all study patients. In 22 febrile patients, blood cultures were also obtained. In vitro activity of moxifloxacin and piperacillin/ sulbactam was determined by agar diffusion. RESULTS： Thirty-one out of 65 patients had positive bile and/or blood cultures. In 31 patients, 63 isolates with 17 different species were identified. The predominant strains were Enterococcus species （26/63）, Ecoli （13/63） and Klebsiella species （8/63）. A comparable in vitro activity of moxifloxacin and piperacillin/sulbactam was observed for E.coli and Klebsiella species. In contrast, Enterococcus species had higher resistances towards moxifloxacin. Overall bacteria showed antibiotic resistances in vitro of 34.9% for piperacillin/sulbactam and 36.5% for moxifioxacin.CONCLUSION： Enterococcus species, E.co/i and Klebsiella species were the most common bacteria isolated from bile and/or blood from patients with acute cholangitis. Overall, a mixed infection with several species was observed, and bacteria showed a comparable in vitro activity for piperacillin/sulbactam and moxifloxacin.展开更多
We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment i...We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.展开更多
BACKGROUND Respiratory tract infections in the elderly are difficult to cure and can easily recur,thereby posing a great threat to patient prognosis and quality of life.AIM To investigate the therapeutic effects of di...BACKGROUND Respiratory tract infections in the elderly are difficult to cure and can easily recur,thereby posing a great threat to patient prognosis and quality of life.AIM To investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection.METHODS Seventy-four elderly patients with respiratory tract infection were randomly allocated to a study(n=37;treated with cefoperazone sodium/sulbactam sodium)or control(n=37;treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support)group.Both groups were treated for 7 d.Time to symptom relief(leukocyte recovery;body temperature recovery;cough and sputum disappearance;and rale disappearance time),treatment effect,and laboratory indexes[procalcitonin(PCT),C-reactive protein(CRP),white blood cell count(WBC),and neutrophil percentage(NE)]before and 7 d after treatment and the incidence of adverse reactions were assessed.RESULTS In the study group,the time to WBC normalization(6.79±2.09 d),time to body temperature normalization(4.15±1.08 d),time to disappearance of cough and sputum(6.19±1.56 d),and time to disappearance of rales(6.68±1.43 d)were shorter than those of the control group(8.89±2.32 d,5.81±1.33 d,8.77±2.11 d,and 8.69±2.12 d,respectively;P=0.000).Total effective rate was higher in the study group(94.59%vs 75.68%,P=0.022).Serum PCT(12.89±3.96μg/L),CRP(19.62±6.44 mg/L),WBC(20.61±6.38×10^(9)/L),and NE(86.14±7.21%)levels of the study group before treatment were similar to those of the control group(14.05±4.11μg/L,18.79±5.96 mg/L,21.21±5.59×10^(9)/L,and 84.39±6.95%,respectively)with no significant differences(P=0.220,0.567,0.668,and 0.291,respectively).After 7 d of treatment,serum PCT,CRP,WBC,and NE levels in the two groups were lower than those before treatment.Serum PCT(2.01±0.56μg/L),CRP(3.11±1.02 mg/L),WBC(5.10±1.83×10^(9)/L),and NE(56.35±7.17%)levels were lower in the study group than in the control group(3.29±0.64μg/L,5.67±1.23 mg/L,8.13±3.01×10^(9)/L,and 64.22±8.08%,respectively;P=0.000).There was no significant difference in the incidence of adverse reactions between the groups(7.50%vs 12.50%,P=0.708).CONCLUSION Piperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.展开更多
Piperacillin is a polar organic substance,and can reduce the interfacial tension of oil and water when dissolved in water.In this study,changes in dichloromethane–water interfacial tensions and microdroplet sizes dur...Piperacillin is a polar organic substance,and can reduce the interfacial tension of oil and water when dissolved in water.In this study,changes in dichloromethane–water interfacial tensions and microdroplet sizes during piperacillin synthesis from an aqueous solution of ampicillin and dichloromethane solution of 4-ethyl-2,3-dioxo-1-piperazine carbonyl chloride(EDPC)were observed using a pendent drop technique and a coaxial ring tube system with embedded high-speed camera,respectively.It was found that the rapid N-acylation reaction caused the piperacillin at the interface to synthesize rapidly and diffuse out slowly,resulting in the interfacial tension decreased from 19.5 m N·m-1 to 7.2 m N·m-1 rapidly and then increased slowly as the concentrations of ampicillin and EDPC were 0.05 mol·L-1 and 0.1 mol·L-1.Meanwhile,the increase in the concentration of EDPC increased the peak concentration of piperacillin at the interface,and the addition of ethyl acetate to the ampicillin solution promoted mass transfer and reduced the aggregation of piperacillin effectively.During synthesis,the interfacial tension decreased,leading to a change in droplet sizes in the micro-reaction system.The two-phase reaction was carried out in a coaxial ring tube,with ampicillin and EDPC solutions as continuous and dispersed phases,respectively.The reaction reduced the dripping flow area,and the addition of ethyl acetate to the ampicillin solution slightly affected the division of the flow pattern.Under the same flow conditions,the droplet sizes of the reaction group were smaller than those of the no reaction group.The experimental results demonstrated that the increase of the continuous phase,decrease in the dispersed phase flow rate,or increase in EDPC concentration making droplet sizes smaller,and the addition of ethyl acetate slightly affected droplet sizes.These findings are important for the design and optimization of piperacillin synthesis reactors.展开更多
To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam,renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats.A b...To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam,renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats.A bacteremia model was established to investigate the pharmacokinetic properties of piperacillin and tazobactam under different conditions.Renal slices were taken to examine the uptake of piperacillin and tazobactam.Pharmacokinetic studies ofβ-lactamase in rats were performed to study the contribution of rOat1/3 to the inhibition of tazobactam onβ-lactamase.The AUC(from 2.93±0.58 to 6.52±1.44 mg·min/ml)and the plasma clearance(CL P)(from 2.41±1.20 to 0.961±0.212 ml/min/kg)of tazobactam were both altered after the intravenous coadministration of piperacillin and tazobactam in the bacteremia rats.The renal clearance(CL R)of tazobactam decreased from 1.30±0.50 to 0.361±0.043 ml/min/kg.In summary,there was a beneficial interaction between piperacillin and tazobactam mediated by rOat1 and rOat3.Piperacillin enhances the inhibitory effect of tazobactam onβ-lactamase through the inhibition of rOat1 and rOat3 in rats.The contribution rate of rOat1/3 for the synergistic effect was 20%when the two drugs were coadministered.展开更多
Antibiotics cause 36 percent of all cases of drug-induced AKI （acute kidney injury）. Research suggests that drug-induced AKI increases hospital length of stay, ventilator days and mortality. The purpose of this stud...Antibiotics cause 36 percent of all cases of drug-induced AKI （acute kidney injury）. Research suggests that drug-induced AKI increases hospital length of stay, ventilator days and mortality. The purpose of this study was to determine which administration method of piperacillin/tazobactam （pip/tazo） would have a higher incidence of AKI in combination with vancomycin. All patients greater than 18 years old admitted to the general medical floor, who were receiving combination therapy were included in the study. Excluded patients comprised： patients with a baseline SCr （serum creatinine） greater than 2 mg/dL, receiving peritoneal dialysis or hemodialysis, an ICU stay, pregnancy, and concomitant use of defined nephrotoxic agents. AKI was defined as an absolute increase in SCr of 0.5 mg/dL or a 50% increase from baseline. The primary outcome of AKI occurred in 18 out of 63 patients （28.6%） in the standard-infusion pip/tazo plus vancomycin group and 9 out of 35 patients （25.7%） in the extended-infusion pip/tazo plus vancomycin group （Z = -0.30, p-value = 0.381）. AKI is very prevalent with one of our most frequently used empiric antibiotic combinations. While this study found no significant difference, as pharmacists, we learned it is still necessary to closely monitor patients＇ receiving this antibiotic combination.展开更多
AIM: To report our experience with empiric antimicrobial monotherapy (piperacillin/tazobactam, of which no data are available in such specific circumstances) in microbiologically-documented infections in patients with...AIM: To report our experience with empiric antimicrobial monotherapy (piperacillin/tazobactam, of which no data are available in such specific circumstances) in microbiologically-documented infections in patients with benign and malignant conditions of the biliary tract.METHODS: Twenty-three patients, 10 with benign and 13 with malignant conditions affecting the biliary tree and microbiologically-documented infections were recruited and the efficacy of empirical antibiotic therapy was assessed.RESULTS: The two groups featured similar demographic and clinical data. Overall, the infective episodes were most due to Gram negative agents, more than 60% of such episodes (mostly in malignant conditions) were preceded by invasive instrumental maneuvers. Empirical antibiotic therapy with a single agent (piperacillin/tazobactam) was effective in more than 80% of cases. No deaths were reported following infections. CONCLUSION: An empiric therapeutic approach with piperacillin/tazobactam is highly effective in biliary tract infections due to benign or malignant conditions.展开更多
Pseudomonas aeruginosa remains an important pathogen. Our purpose was to determine the minimum inhibitory con-centration (MIC) and pharmacodynamic (PD) parameters predicting a positive response to therapy with piperac...Pseudomonas aeruginosa remains an important pathogen. Our purpose was to determine the minimum inhibitory con-centration (MIC) and pharmacodynamic (PD) parameters predicting a positive response to therapy with piperacil-lin-tazobactam. Medical records were retrospectively reviewed at 3 centers. Data were recorded to assess age, type of disease, renal function, weight (body mass), MIC, antimicrobial treatment, and clinical outcome. Success was response to piperacillin-tazobactam alone, or in combination with another active agent;failure was lack of response. Of 78 eva-luable patients, 63 responded (7 UTI;56 non-UTI) and 15 did not;26 responding received combination therapy and 37 monotherapy. Piperacillin-tazobactam treatment was successful in 53 of 63 of non-UTI disease with a MIC of ≤64/4 μg/mL, but in only 3 of 7 with a MIC of >64/4 μg/mL (P = 0.023);overall 9 of 10 infections by strains with MICs = 32 - 64 μg/mL had a successful outcome. Piperacillin estimated time above MIC at 20% separated those responding from those that did not (P = 0.019).展开更多
Piperacillin/tazobactam and ciprofloxacin are often used in combination as initial empiric anti-biotic therapy in critical ill patients. Especially in patients undergoing continuous renal replacement therapy (CRRT) th...Piperacillin/tazobactam and ciprofloxacin are often used in combination as initial empiric anti-biotic therapy in critical ill patients. Especially in patients undergoing continuous renal replacement therapy (CRRT) the pharmacokinetics of antimicrobial agents can be highly variable. In order to avoid under- or overdosage of antibiotics therapeutic drug monitoring (TDM) is highly re-commendable. Based on two known HPLC assays for piperacillin a new method in combination with solid phase extraction (SPE) for the simultaneous determination of piperacillin and ciprofloxacin was developed. Method validation was performed according to the EMA guideline on validation of bioanalytical methods. The HPLC column used was a Perfect Bond ODS-HD C18 analytical column (100 mm × 4.6 mm i.d., particle size 5 μm), equipped with a guard column (10 mm × 4.6 mm, particle size 5 μm) containing the same packing material. Detection wavelength was set at 228 nm for piperacillin and benzylpenicillin was used as internal standard (IS). Ciprofloxacin was determined at two wavelengths (280 nm, 315 nm). This newly developed HPLC method in combination with SPE-extraction allows an accurate, precise, specific and efficient determination of piperacillin and ciprofloxacin in biological matrices. Results allow the calculation of all relevant pharmacokinetic data for critically ill patients undergoing CRRT and the optimization of dosing and TDM.展开更多
基金National Natural Science Foundation of China(31860071)Ministry of Education New Agricultural Research and Reform Practice Program(2020114)+4 种基金Surface Program of Inner Mongolia Natural Science Foundation(2021MS03008)Inner Mongolia Autonomous Region Grassland Talent Innovation Team-Rolling Support Program for Castor Molecular Breeding Research Innovation Talent Teams(2022)2023 Inner Mongolia Autonomous Region Science and Technology Department Establishes the Project of Key Laboratory Construction of Castor Breeding and Comprehensive Utilization in Inner Mongolia Autonomous RegionInner Mongolia University for Nationalities 2022 Basic Research Operating Expenses of Colleges and Universities directly under the Autonomous Region Project(237)Open Fund Project of Castor Industry Collaborative Innovation Center of Inner Mongolia Autonomous Region(MDK2021011,MDK2022014).
文摘Castor is one of the top 10 oil crops in the world and has extremely valuable uses.Castor inflorescences directly affect yield,so the study of inflorescence development is very important in increasing castor yield.Our previous studies have shown that the PIP5K gene family(PIP5Ks)is associated with inflorescence development.In this study,to determine the function of each PIP5K gene in castor,a female Lm-type castor line,aLmAB2,was used to determine the relative expression levels of the PIP5Ks in castor inflorescences.Six PIP5K genes were heterologously overexpressed in Arabidopsis thaliana,the relative expression of each gene and the effect on plants was determined in A.thaliana,and the relationships among the PIP5Ks in castor were inferred.The expression levels of the PIP5Ks in the female Lm-type castor line aLmAB2 were analyzed.The relative expression levels of the PIP5K9 and PIP5K11 genes were high(p<0.05)in isofemale inflorescences,and those of PIP5K1,PIP5K2,PIP5K6,and PIP5K8 were high(p<0.05)in female inflorescences but low(p<0.05)in bisexual inflorescences.The PIP5Ks were heterologously overexpressed in A.thaliana,and T3-generation plants with stable genetic resistance,i.e.,AT-PIP5K^(+)plants(AT-PIP5K1^(+),AT-PIP5K2^(+),AT-PIP5K6^(+),AT-PIP5K8^(+),AT-PIP5K9^(+),and ATPIP5K11^(+) plants),were obtained.Biological tests of the AT-PIP5K+plants showed that the growth of the main stem was significantly delayed in AT-PIP5K+plants compared with Columbia wild-type(WT)A.thaliana plants;the PIP5K1 and PIP5K2 genes promoted lateral stem growth and flower and silique development;and the PIP5K6,PIP5K8,PIP5K9 and PIP5K11 genes inhibited lateral stem growth and flower and silique development.The correlations among PIP5Ks in castor suggest that there may be a synergistic relationship among PIP5K1,PIP5K2,and PIP5K6 in castor inflorescences,and PIP5K8,PIP5K9,and PIP5K11 are complementary to the other three genes.
文摘AIM：To analyze the in vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens isolated from patients with acute cholangitis. METHODS： In this prospective study a total of 65 patients with acute cholangitis due to biliary stone obstruction （n = 7）, benign biliary stricture （n = 16）, and malignant biliary stricture （n = 42） were investigated with regard to spectrum of bacterial infection and antibiotic resistance. Pathogens were isolated from bile cultures in all study patients. In 22 febrile patients, blood cultures were also obtained. In vitro activity of moxifloxacin and piperacillin/ sulbactam was determined by agar diffusion. RESULTS： Thirty-one out of 65 patients had positive bile and/or blood cultures. In 31 patients, 63 isolates with 17 different species were identified. The predominant strains were Enterococcus species （26/63）, Ecoli （13/63） and Klebsiella species （8/63）. A comparable in vitro activity of moxifloxacin and piperacillin/sulbactam was observed for E.coli and Klebsiella species. In contrast, Enterococcus species had higher resistances towards moxifloxacin. Overall bacteria showed antibiotic resistances in vitro of 34.9% for piperacillin/sulbactam and 36.5% for moxifioxacin.CONCLUSION： Enterococcus species, E.co/i and Klebsiella species were the most common bacteria isolated from bile and/or blood from patients with acute cholangitis. Overall, a mixed infection with several species was observed, and bacteria showed a comparable in vitro activity for piperacillin/sulbactam and moxifloxacin.
文摘We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.
文摘BACKGROUND Respiratory tract infections in the elderly are difficult to cure and can easily recur,thereby posing a great threat to patient prognosis and quality of life.AIM To investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection.METHODS Seventy-four elderly patients with respiratory tract infection were randomly allocated to a study(n=37;treated with cefoperazone sodium/sulbactam sodium)or control(n=37;treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support)group.Both groups were treated for 7 d.Time to symptom relief(leukocyte recovery;body temperature recovery;cough and sputum disappearance;and rale disappearance time),treatment effect,and laboratory indexes[procalcitonin(PCT),C-reactive protein(CRP),white blood cell count(WBC),and neutrophil percentage(NE)]before and 7 d after treatment and the incidence of adverse reactions were assessed.RESULTS In the study group,the time to WBC normalization(6.79±2.09 d),time to body temperature normalization(4.15±1.08 d),time to disappearance of cough and sputum(6.19±1.56 d),and time to disappearance of rales(6.68±1.43 d)were shorter than those of the control group(8.89±2.32 d,5.81±1.33 d,8.77±2.11 d,and 8.69±2.12 d,respectively;P=0.000).Total effective rate was higher in the study group(94.59%vs 75.68%,P=0.022).Serum PCT(12.89±3.96μg/L),CRP(19.62±6.44 mg/L),WBC(20.61±6.38×10^(9)/L),and NE(86.14±7.21%)levels of the study group before treatment were similar to those of the control group(14.05±4.11μg/L,18.79±5.96 mg/L,21.21±5.59×10^(9)/L,and 84.39±6.95%,respectively)with no significant differences(P=0.220,0.567,0.668,and 0.291,respectively).After 7 d of treatment,serum PCT,CRP,WBC,and NE levels in the two groups were lower than those before treatment.Serum PCT(2.01±0.56μg/L),CRP(3.11±1.02 mg/L),WBC(5.10±1.83×10^(9)/L),and NE(56.35±7.17%)levels were lower in the study group than in the control group(3.29±0.64μg/L,5.67±1.23 mg/L,8.13±3.01×10^(9)/L,and 64.22±8.08%,respectively;P=0.000).There was no significant difference in the incidence of adverse reactions between the groups(7.50%vs 12.50%,P=0.708).CONCLUSION Piperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.
基金financially supported by the National Key Research and Development Program of China(2019YFA0905100)the National Natural Science Foundation of China(21878169 and 21991102)Tsinghua University Initiative Scientific Research Program(2018Z05JZY010)。
文摘Piperacillin is a polar organic substance,and can reduce the interfacial tension of oil and water when dissolved in water.In this study,changes in dichloromethane–water interfacial tensions and microdroplet sizes during piperacillin synthesis from an aqueous solution of ampicillin and dichloromethane solution of 4-ethyl-2,3-dioxo-1-piperazine carbonyl chloride(EDPC)were observed using a pendent drop technique and a coaxial ring tube system with embedded high-speed camera,respectively.It was found that the rapid N-acylation reaction caused the piperacillin at the interface to synthesize rapidly and diffuse out slowly,resulting in the interfacial tension decreased from 19.5 m N·m-1 to 7.2 m N·m-1 rapidly and then increased slowly as the concentrations of ampicillin and EDPC were 0.05 mol·L-1 and 0.1 mol·L-1.Meanwhile,the increase in the concentration of EDPC increased the peak concentration of piperacillin at the interface,and the addition of ethyl acetate to the ampicillin solution promoted mass transfer and reduced the aggregation of piperacillin effectively.During synthesis,the interfacial tension decreased,leading to a change in droplet sizes in the micro-reaction system.The two-phase reaction was carried out in a coaxial ring tube,with ampicillin and EDPC solutions as continuous and dispersed phases,respectively.The reaction reduced the dripping flow area,and the addition of ethyl acetate to the ampicillin solution slightly affected the division of the flow pattern.Under the same flow conditions,the droplet sizes of the reaction group were smaller than those of the no reaction group.The experimental results demonstrated that the increase of the continuous phase,decrease in the dispersed phase flow rate,or increase in EDPC concentration making droplet sizes smaller,and the addition of ethyl acetate slightly affected droplet sizes.These findings are important for the design and optimization of piperacillin synthesis reactors.
基金supported by the National Natural Science Foundation of China(Nos.81874324,81473280,U1608283,81603186)
文摘To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam,renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats.A bacteremia model was established to investigate the pharmacokinetic properties of piperacillin and tazobactam under different conditions.Renal slices were taken to examine the uptake of piperacillin and tazobactam.Pharmacokinetic studies ofβ-lactamase in rats were performed to study the contribution of rOat1/3 to the inhibition of tazobactam onβ-lactamase.The AUC(from 2.93±0.58 to 6.52±1.44 mg·min/ml)and the plasma clearance(CL P)(from 2.41±1.20 to 0.961±0.212 ml/min/kg)of tazobactam were both altered after the intravenous coadministration of piperacillin and tazobactam in the bacteremia rats.The renal clearance(CL R)of tazobactam decreased from 1.30±0.50 to 0.361±0.043 ml/min/kg.In summary,there was a beneficial interaction between piperacillin and tazobactam mediated by rOat1 and rOat3.Piperacillin enhances the inhibitory effect of tazobactam onβ-lactamase through the inhibition of rOat1 and rOat3 in rats.The contribution rate of rOat1/3 for the synergistic effect was 20%when the two drugs were coadministered.
文摘Antibiotics cause 36 percent of all cases of drug-induced AKI （acute kidney injury）. Research suggests that drug-induced AKI increases hospital length of stay, ventilator days and mortality. The purpose of this study was to determine which administration method of piperacillin/tazobactam （pip/tazo） would have a higher incidence of AKI in combination with vancomycin. All patients greater than 18 years old admitted to the general medical floor, who were receiving combination therapy were included in the study. Excluded patients comprised： patients with a baseline SCr （serum creatinine） greater than 2 mg/dL, receiving peritoneal dialysis or hemodialysis, an ICU stay, pregnancy, and concomitant use of defined nephrotoxic agents. AKI was defined as an absolute increase in SCr of 0.5 mg/dL or a 50% increase from baseline. The primary outcome of AKI occurred in 18 out of 63 patients （28.6%） in the standard-infusion pip/tazo plus vancomycin group and 9 out of 35 patients （25.7%） in the extended-infusion pip/tazo plus vancomycin group （Z = -0.30, p-value = 0.381）. AKI is very prevalent with one of our most frequently used empiric antibiotic combinations. While this study found no significant difference, as pharmacists, we learned it is still necessary to closely monitor patients＇ receiving this antibiotic combination.
文摘AIM: To report our experience with empiric antimicrobial monotherapy (piperacillin/tazobactam, of which no data are available in such specific circumstances) in microbiologically-documented infections in patients with benign and malignant conditions of the biliary tract.METHODS: Twenty-three patients, 10 with benign and 13 with malignant conditions affecting the biliary tree and microbiologically-documented infections were recruited and the efficacy of empirical antibiotic therapy was assessed.RESULTS: The two groups featured similar demographic and clinical data. Overall, the infective episodes were most due to Gram negative agents, more than 60% of such episodes (mostly in malignant conditions) were preceded by invasive instrumental maneuvers. Empirical antibiotic therapy with a single agent (piperacillin/tazobactam) was effective in more than 80% of cases. No deaths were reported following infections. CONCLUSION: An empiric therapeutic approach with piperacillin/tazobactam is highly effective in biliary tract infections due to benign or malignant conditions.
文摘Pseudomonas aeruginosa remains an important pathogen. Our purpose was to determine the minimum inhibitory con-centration (MIC) and pharmacodynamic (PD) parameters predicting a positive response to therapy with piperacil-lin-tazobactam. Medical records were retrospectively reviewed at 3 centers. Data were recorded to assess age, type of disease, renal function, weight (body mass), MIC, antimicrobial treatment, and clinical outcome. Success was response to piperacillin-tazobactam alone, or in combination with another active agent;failure was lack of response. Of 78 eva-luable patients, 63 responded (7 UTI;56 non-UTI) and 15 did not;26 responding received combination therapy and 37 monotherapy. Piperacillin-tazobactam treatment was successful in 53 of 63 of non-UTI disease with a MIC of ≤64/4 μg/mL, but in only 3 of 7 with a MIC of >64/4 μg/mL (P = 0.023);overall 9 of 10 infections by strains with MICs = 32 - 64 μg/mL had a successful outcome. Piperacillin estimated time above MIC at 20% separated those responding from those that did not (P = 0.019).
文摘Piperacillin/tazobactam and ciprofloxacin are often used in combination as initial empiric anti-biotic therapy in critical ill patients. Especially in patients undergoing continuous renal replacement therapy (CRRT) the pharmacokinetics of antimicrobial agents can be highly variable. In order to avoid under- or overdosage of antibiotics therapeutic drug monitoring (TDM) is highly re-commendable. Based on two known HPLC assays for piperacillin a new method in combination with solid phase extraction (SPE) for the simultaneous determination of piperacillin and ciprofloxacin was developed. Method validation was performed according to the EMA guideline on validation of bioanalytical methods. The HPLC column used was a Perfect Bond ODS-HD C18 analytical column (100 mm × 4.6 mm i.d., particle size 5 μm), equipped with a guard column (10 mm × 4.6 mm, particle size 5 μm) containing the same packing material. Detection wavelength was set at 228 nm for piperacillin and benzylpenicillin was used as internal standard (IS). Ciprofloxacin was determined at two wavelengths (280 nm, 315 nm). This newly developed HPLC method in combination with SPE-extraction allows an accurate, precise, specific and efficient determination of piperacillin and ciprofloxacin in biological matrices. Results allow the calculation of all relevant pharmacokinetic data for critically ill patients undergoing CRRT and the optimization of dosing and TDM.
