Tazobactam,β lactamase inhibitor, was synthesized from 6 aminopenicillanic acid through eleven steps, including diazotization, bromination, oxidation, chlorization, cyclization, deprotection and so on. The designed...Tazobactam,β lactamase inhibitor, was synthesized from 6 aminopenicillanic acid through eleven steps, including diazotization, bromination, oxidation, chlorization, cyclization, deprotection and so on. The designed route was examined, particularly the azide substitution and cyclization. In the latter reaction, vinyl acetic ester was employed in place of acetylene.展开更多
A reversed-phase high performance liquid chromatographic (RP-HPLC) method wasdeveloped and validated for the simultaneous deteimination of ceftazidime and tazobactam ininject-able powder. Methods Chromatography was ca...A reversed-phase high performance liquid chromatographic (RP-HPLC) method wasdeveloped and validated for the simultaneous deteimination of ceftazidime and tazobactam ininject-able powder. Methods Chromatography was carried out on Zorbax 300SB-C_(18) column using amixture of methanol and aqueous solution of phosphate buffer (pH = 5.6) as mobile phase. The UVdetection wavelength was 220 run. Results The linear ranges of ceftazidime and tazobactam were 0.62- 631.8 μg·mL^(-1) and 0.66 - 677.50 μg·mL^(-1), respectively. The average recoveries were 98.8%- 101.4% for ceftazidime, and 99,1% - 100.2% for tazobactam. The RSD values of inter-day andintra-day assays were lower than 1.5% for ceftazidime and 2.6% for tazobactam. Conclusion Thismethod is reproducible, simple, precise, and rapid for the quality control of ceftazidime andtazobactam in injectable powder.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
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
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
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
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
Background:Studies have demonstrated improved clinical outcomes with extended infusion(EI)piperacillin/tazobactam(TZP)compared to standard infusion(SI).However,there is less evidence on its benefits in noncritically-i...Background:Studies have demonstrated improved clinical outcomes with extended infusion(EI)piperacillin/tazobactam(TZP)compared to standard infusion(SI).However,there is less evidence on its benefits in noncritically-ill patients.Hospital-wide EI TZP was implemented at our site on February 21,2012.Our objectives were to compare clinical,safety and economic outcomes between EI and SI TZP.Methods:A retrospective cohort study of all adult patients who received EI TZP(3.375 g IV q8h infused over 4 hours and SI TZP for≥48 hours during 3 years pre-and postimplementation was conducted.The primary study outcome was 14-day mortality while secondary outcomes included length of hospital stay(LOS),nursing plus pharmacy cost,occurrence of Clostridioides difficile infection,readmission within 30 days and change in Pseudomonas aeruginosa minimum inhibitory concentration(MIC)distribution for TZP.The primary outcome and binary secondary outcomes were analyzed using a logistic regression model.LOS was examined using time to event analysis.Cost was examined using linear regression modelling.Results:Overall,2034 patients received EI TZP and 1364 patients received SI TZP.EI TZP was associated with lower odds of mortality(OR 0.76,95%CI 0.63-0.91),lower odds of C.difficile infection(OR 0.59,95%CI 0.41-0.84)and 8%lower cost(estimate 0.92,95%CI 0.87-0.98)compared to SI TZP.Conclusions:Hospital-wide implementation of EI TZP was associated with lower odds of 14-day mortality and incidence of C.difficile infection with cost savings at our institution.展开更多
文摘Tazobactam,β lactamase inhibitor, was synthesized from 6 aminopenicillanic acid through eleven steps, including diazotization, bromination, oxidation, chlorization, cyclization, deprotection and so on. The designed route was examined, particularly the azide substitution and cyclization. In the latter reaction, vinyl acetic ester was employed in place of acetylene.
文摘A reversed-phase high performance liquid chromatographic (RP-HPLC) method wasdeveloped and validated for the simultaneous deteimination of ceftazidime and tazobactam ininject-able powder. Methods Chromatography was carried out on Zorbax 300SB-C_(18) column using amixture of methanol and aqueous solution of phosphate buffer (pH = 5.6) as mobile phase. The UVdetection wavelength was 220 run. Results The linear ranges of ceftazidime and tazobactam were 0.62- 631.8 μg·mL^(-1) and 0.66 - 677.50 μg·mL^(-1), respectively. The average recoveries were 98.8%- 101.4% for ceftazidime, and 99,1% - 100.2% for tazobactam. The RSD values of inter-day andintra-day assays were lower than 1.5% for ceftazidime and 2.6% for tazobactam. Conclusion Thismethod is reproducible, simple, precise, and rapid for the quality control of ceftazidime andtazobactam in injectable powder.
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.
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.
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Background:Studies have demonstrated improved clinical outcomes with extended infusion(EI)piperacillin/tazobactam(TZP)compared to standard infusion(SI).However,there is less evidence on its benefits in noncritically-ill patients.Hospital-wide EI TZP was implemented at our site on February 21,2012.Our objectives were to compare clinical,safety and economic outcomes between EI and SI TZP.Methods:A retrospective cohort study of all adult patients who received EI TZP(3.375 g IV q8h infused over 4 hours and SI TZP for≥48 hours during 3 years pre-and postimplementation was conducted.The primary study outcome was 14-day mortality while secondary outcomes included length of hospital stay(LOS),nursing plus pharmacy cost,occurrence of Clostridioides difficile infection,readmission within 30 days and change in Pseudomonas aeruginosa minimum inhibitory concentration(MIC)distribution for TZP.The primary outcome and binary secondary outcomes were analyzed using a logistic regression model.LOS was examined using time to event analysis.Cost was examined using linear regression modelling.Results:Overall,2034 patients received EI TZP and 1364 patients received SI TZP.EI TZP was associated with lower odds of mortality(OR 0.76,95%CI 0.63-0.91),lower odds of C.difficile infection(OR 0.59,95%CI 0.41-0.84)and 8%lower cost(estimate 0.92,95%CI 0.87-0.98)compared to SI TZP.Conclusions:Hospital-wide implementation of EI TZP was associated with lower odds of 14-day mortality and incidence of C.difficile infection with cost savings at our institution.
