Cefoperazone sodium/sulbactam sodium vs piperacillin sodium/tazobactam sodium for treatment of respiratory tract infection in elderly patients

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.

Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam Versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies

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.

Piperacillin enhances the inhibitory effect of tazobactam on β-lactamase through inhibition of organic anion transporter 1/3 in rats

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.

Assessment of Susceptibility, Pharmacodynamics, and Therapeutic Response for Interpretation of Piperacillin-Tazobactam <i>in Vitro</i>Activity in the Treatment of <i>Pseudomonas aeruginosa</i>Infection

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).

Retrospective Evaluation of Acute Kidney Injury： Extended Infusion versus Standard Infusion Piperacillin/Tazobactam with Vancomycin

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.

Empirical antibiotic treatment with piperacillin-tazobactam in Patients with microbiologically-documented biliary tract infections

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.

β-内酰胺酶抑制剂tazobactam与舒巴坦的比较研究

用琼脂二倍稀释法研究了ｔａｚｏｂａｃｔａｍ、舒巴坦与头孢哌酮、哌拉西林、头孢唑林、氨苄西林对６６株双重耐药菌的体外协同抗菌作用。研究结果表明：除铜绿假单胞菌外，ｔａｚｏ－ｂａｃ－ｔａｍ、舒巴坦与４种β－内酰胺类抗生素均有不同程度的协同增效作用。其中ｔａｚｏｂａｃｔａｍ与头孢哌酮的协同作用最强，可使头孢哌酮对大肠杆菌的ＭＩＣ５０从３２ｍｇ／Ｌ降至０．５ｍｇ／Ｌ。头孢哌酮与舒巴坦、哌拉西林与ｔａｚｏｂａｃｔａｍ的协同作用其次，氨苄西林与舒巴坦的协同作用较弱。并且随着ｔａｚｏｂａｃｔａｍ的浓度增大，其抑制作用逐渐增强。

Synthesis of Tazobactam,β-Lactamase Inhibitor

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.

新型抗菌药物Ceftolozane/tazobactam的研究进展

目的:了解新型抗菌药物Ceftolozane/tazobactam的研究进展。方法:查阅近年来国外相关文献,对Ceftolozane/tazobactam的作用机制、抗菌活性、临床研究、药动学、药效学以及不良反应等方面的研究进行归纳和总结。结果:Ceftolozane/tazobactam是头孢洛扎硫酸盐和β-内酰胺酶抑制剂他唑巴坦钠组成的复方制剂。硫酸头孢洛扎主要通过青霉素结合蛋白抑制细胞壁生物合成产生杀菌作用,他唑巴坦钠是某些β-内酰胺酶的不可逆抑制剂,对不同的革兰氏阴性、阳性菌和厌氧菌均具有抗菌活性。Ceftolozane/tazobactam对铜绿假单胞菌、产超广谱β-内酰胺酶的肠杆菌科细菌感染疗效确切;对复杂性尿路感染的临床治愈率和微生物根除率均优于左氧氟沙星;对多重耐药菌病原微生物及左氧氟沙星耐药的病原微生物有较好的疗效;与甲硝唑联用治疗复杂性腹腔感染具有一定的研究前景,为临床感染性疾病的治疗带来了新的选择。结论:Ceftolozane/tazobactam作为一种新型抗菌药物,为临床感染性疾病的治疗带来了新的选择,具有较高的临床研究价值。

Tazobactam/哌拉西林的药理和临床应用

哌拉西林(PIPC)是日本富山化学工业株式会社开发的β-内酰胺类抗生素,经临床使用多年,其安全性、有效性得到了较高评价.PIPC对各种细菌耐药株产生的β-内酰胺酶均不稳定.目前,全球有90%以上金葡球菌对青霉素耐药,因此,由细菌产生β-内酰胺酶类导致耐药问题日趋严重.为解决耐药问题,已成功开发并应用了数种β-内酰胺酶抑制剂与青霉素类或头孢菌素类复合制剂,扩大了抗菌谱,增强了抗菌活性.紧随舒巴坦(SBT)和克拉维酸(CVA)后,日本大鹏药品工业株式会社开发的新型β-内酰胺酶抑制剂tazobac-tam(TAZ)并与PIPC制成合剂(1:8),目前已在西班牙、英国、法国、德国等国家上市.TAZ/PIPC比已使用的Unasyn(舒巴坦/氨苄西林),Aug-mentin(克拉维酸/阿莫西林)等具有更广的抗菌谱和适应症.现将TAZ/PIPC的药理和临床应用综述如下.

哌拉西林与酶抑制剂Tazobactam的复合制剂

随着β-内酰胺类抗生素的广泛使用,以细菌产生灭活酶为主的耐药问题日益严重.β-内酰胺酶抑制剂与β-内酰胺类药物联用,增强后者抗菌活性.扩大其抗菌谱,已成为提高抗感染疗效的重要手段.Tazobactam(TAZ)是继克拉维酸、舒巴坦(Sulbactam)之后的又一种β-内酰胺酶抑制剂.该品由日本大凤公司开发并转让给美国Cyanamid公司生产.目前它与哌拉西林(PIP)的复合制剂(PIP/TAZ)已完成了临床试用,呈现出良好的临床应用前景.本文就该品的抗菌作用、药代动力学特点和临床应用情况等方面作一介绍.

Simultaneous Determination of Ceftazidime and Tazobactam in Injectable Powder by Reversed-Phase High Performance Liquid Chromatography

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.

In vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens of acute cholangitis

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.

新酶抑制剂Tazobactam的特性及其与哌拉西林的复合制剂

随着β-内酰胺类抗生素的广泛应用,许多微生物产生的各种β-内酰胺酶已形成了一个酶系家族,它们水解β-内酰胺类的内酰胺环使之丧失活性。而且,新β-内酰胺类的开发和应用,总是伴随着新β-内酰胺酶的产生和发展。目前全球有90％以上金葡菌对青霉素耐药。因此,由细菌产生β-内酰胺酶类导致耐药问题日趋严重。

Effects of piperacillin synthesis on the infterfacial tensions and droplet sizes

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.

哌拉西林与tazobactam复合制剂Tazocin

许多细菌产生的β-内酰胺酶(简称β-lase)水解β-内酰胺类抗生素的β-内酰胺环,使其丧失活性,是耐药性产生的机制之一.在克服β-lase所致耐药性的方法中,最有效的是应用β-内酰胺类抗生素与β-lase抑制剂的复合制剂.不可逆的竞争性β-lase抑制剂tazobactam(TAZ,YTR830)是继克拉维酸、舒巴坦后发现的作用谱更广和抑酶活性更强的β-lase抑制剂.哌拉西林(PIPC)与TAZ复合制剂tazocin(tazocillin,Zosyn,以下简称P/T),于1992年由日本大鹏药品开发,其后转让给美国Cyanamid、Lederle公司生产,目前已在欧美等许多国家应用.俄罗斯Yakovlev根据俄罗斯临床应用经验、美国Lederle公司提供的资料和最近大量文献报道,对其抗菌活性、药动学和临床应用等作了扼要的介绍.

哌拉西林/tazobactam对从住院患者分离的5626株菌的抗菌活性比较

<正>哌拉西林(PIPC)/tazobactam(TAZ)是PIPC的复合制剂.脲基青霉素具有广谱高活性,TAZ是一个新的β-内酰胺酶抑制剂,呈现抗质粒中介酶及Ⅰ类诱导酶活性.PIPC/TAZ体外对各种产β-内酰胺酶菌株活性极强.Verbist等测定了PIPC/TAZ的敏感性,并与单一的PIPC、阿莫西林/克拉维酸盐、头孢他啶、亚胺培南及环丙沙星对临床分离菌株的体外抗菌活性作出比较.实验由比利时及卢森堡的58家医院微生物实验室共同完成.考察了PIPC/TAZ及其它抗生素对新分离5625株革兰阴性及阳性菌的活性.肠杆菌科中可诱导Ⅰ类β-内酰胺酶的微生物对PIPC/TAZ、头孢他啶、亚胺培南及环丙沙星敏感度的百分率很相近,一般在81%~84%;不能诱导酶产生的菌类为93%~97%.PIPC/TAZ对铜绿假单胞菌的活性与头孢他啶类似、比亚胺培南或环丙沙星强;对革兰阳性葡萄球菌及肠球菌的活性较头孢他啶更高,看来它会成为一个很有希望的院内感染用抗生素.

不同配比哌拉西林钠他唑巴坦钠在重症肺炎治疗中的安全性及影响因素研究

目的:探讨不同配比哌拉西林钠他唑巴坦钠在重症肺炎患者治疗中的安全性及其影响因素。方法:回顾性调查2021年8月至2022年8月中国医科大学附属第一医院应用不同配比哌拉西林钠他唑巴坦钠治疗的重症肺炎患者的不良反应(粒细胞缺乏、血小板计数降低、过敏和腹泻)发生情况。根据治疗方案(复方制剂相关配比)分为治疗1组[采用哌拉西林钠他唑巴坦钠(4∶1)治疗]和治疗2组[采用哌拉西林钠他唑巴坦钠(8∶1)治疗]。统计分析患者年龄、性别、既往疾病、用药剂量、用药疗程等与各不良反应相关性。结果:治疗1组患者的总不良反应发生率为79.61%(609/765),低于治疗2组(84.55%,476/563),差异有统计学意义(P<0.05)。单因素Logistic回归分析结果显示,哌拉西林钠他唑巴坦钠(8∶1)的复方制剂配比(OR=1.098,P=0.012)、住院时间延长(OR=1.029,P<0.001)是不良反应发生的独立危险因素(P<0.05);多因素Logistic回归分析结果显示,年龄增长(OR=1.012,P=0.011)、用药疗程延长(OR=1.036,P=0.013)是总不良反应发生的影响因素。结论:哌拉西林钠他唑巴坦钠(4∶1)治疗重症肺炎具有更高的安全性。较长的用药疗程和住院时间可能增加应用哌拉西林钠他唑巴坦钠治疗患者的不良反应发生风险。