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.

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.

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).

A Liquid Chromatography Assay for the Simultaneous Quantification of Piperacillin and Ciprofloxacin in Human Plasma and Dialysate in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy

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.

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), E.coli (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 moxifloxacin.CONCLUSION: Enterococcus species , E.coli 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.

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.

Impact of extended-infusion piperacillin-tazobactam in a Canadian community hospital

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.

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。

Tazobactam/Piperacillin复剂的儿科药代动力学和临床疗效

本文概述了Tazobactam/Piperacillin复剂儿科领域药代动力学和临床应用研究。

原子吸收光谱法测定注射用哌拉西林钠中钠含量

目的建立原子吸收分光光度法测定注射用哌拉西林钠中钠含量,同时对国产制剂成盐情况进行评价。方法原子吸收分光光度法(atomic absorption spectrophotometry,AAS)。采用钠元素空心阴极灯光源;空气-乙炔火焰原子化器;检测波长589.0 nm;4%氯化铯溶液作为电离抑制剂,临用稀释50倍。结果原研企业4批次样品中钠含量平均值4.46%,16家国内生产企业204批次样品中钠元素含量平均值4.41%,均高于理论值4.26%,不同生产企业的产品钠含量差异大,多批次超出理论值±5%范围。结论该方法操作简单、专属性强、结果准确,可通过钠含量的测定,对哌拉西林钠原料成盐工艺水平进行评估。

宣壅清肺汤治疗老年重症肺炎临床观察

目的观察宣壅清肺汤治疗老年重症肺炎的临床效果。方法2021年1月—2022年1月医院收治的老年重症肺炎患者120例随机分为抗生素治疗组(60例)和联合宣壅清肺治疗组(60例)。联合宣壅清肺治疗组采用常规治疗联合宣壅清肺汤治疗,抗生素治疗组进行常规治疗,两组均治疗2周。统计两组治疗2周后的疗效,比较两组治疗前和治疗2周后中医证候积分、血清炎性因子水平、肺功能、血气指标及病情情况。结果治疗2周后,联合宣壅清肺治疗组总有效率为93.33%(56/60),高于抗生素治疗组[80.00%(48/60),P<0.05]。治疗2周后与治疗前比较,两组咳嗽、发热、痰黄或黏稠带血、气喘息粗、胸闷烦躁、口干渴评分及血清可溶性细胞间黏附分子-1(soluble intercellular adhesion molecule-1,sICAM-1)、干扰素-γ(interferon-γ,IFN-γ)、血小板活化因子(platelet activating factor,PAF)、高迁移率族蛋白B1(high mobility group protein B1,HMGB1)水平、二氧化碳分压(carbon dioxide partial pressure,PaCO_(2))、急性生理学及慢性健康状况(scores of acute physiology and chronic health status,APACHEⅡ)、全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)、临床肺部感染(clinical pulmonary infection,CPIS)、肺炎严重指数(pneumonia severity index,PSI)评分降低,联合宣壅清肺治疗组低于抗生素治疗组(P<0.05);两组第1秒用力呼气容积(first second forced expiratory volume,FEV1)、用力肺活量(forced vital capacity,FVC)、氧分压(oxygen partial pressure,PaO_(2))升高,联合宣壅清肺治疗组高于抗生素治疗组(P<0.05)。结论宣壅清肺汤可改善老年重症肺炎患者中医证候,通过降低机体炎症反应提高其肺功能及血气指标,疗效较好。

两种抗感染药物治疗重症肺炎的效果及炎症因子水平预后比较

目的:探究哌拉西林钠他唑巴坦与亚胺培南西司他丁钠治疗重症肺炎的效果及对炎症因子水平、预后的影响。方法:选取2020年1月至2023年3月我院收治的105例重症肺炎患者,用随机数字表法分为A组(n=53)和B组(n=52),A组用亚胺培南西司他丁钠治疗,B组用哌拉西林钠他唑巴坦钠治疗。比较两组患者临床症状消失时间(咳嗽、肺阴影、肺啰音、体温恢复时间),比较治疗前和治疗7d后,两组患者严重程度[肺部感染量表(CPIS)、急性生理学及慢性健康状况(APACHEⅡ)、Murray肺损伤量表(MLIS)]、血气指标[氧饱和度(SpO_(2))、血氧分压(PaO_(2))、二氧化碳分压(PaCO_(2))]及炎症因子[白细胞总数(WBC)、C-反应蛋白(CRP)、降钙素原(PCT)]水平,统计不良反应发生情况。结果:B组咳嗽、肺阴影、肺啰音消失时间及体温恢复时间均短于A组(P均<0.05);治疗7d后,两组患者CPIS、APACHEⅡ、MLIS评分、PaCO_(2)、炎症因子(WBC、CRP、PCT)水平均显著降低,B组水平变化大于A组(P均<0.05);部分血气指标(SpO_(2)、PaO_(2))水平显著升高,B组水平变化大于A组(P均<0.05);两组患者不良反应发生率无显著性差异(P>0.05)。结论:哌拉西林钠他唑巴坦钠与亚胺培南西司他丁钠均可减轻重症肺炎患者病情及临床症状,改善血气状况,缓解炎症反应,但哌拉西林钠他唑巴坦钠效果更佳。

β-内酰胺类抗生素/β-内酰胺酶抑制剂复方制剂点评标准的建立及应用分析

目的建立β-内酰胺类抗生素/β-内酰胺酶抑制剂复方制剂的点评标准,结合临床应用情况,分析其应用效果,促进临床合理使用β-内酰胺类抗生素/β-内酰胺酶抑制剂复方制剂。方法参照相关指南及专家共识,制订β-内酰胺类抗生素/β-内酰胺酶抑制剂复方制剂的药物利用评价(DUE)标准。通过建立的DUE标准,采用回顾性研究方法,评价2019年7—12月南华大学附属第二医院使用头孢哌酮/舒巴坦和哌拉西林/他唑巴坦的894例病例的用药合理性。结果894例病例中,适应证合理率为93.62%,给药剂量合理率为90.49%,用药疗程合理率为89.37%,微生物送检合理率为75.84%。结论建立的头孢哌酮/舒巴坦和哌拉西林/他唑巴坦DUE标准能够作为临床合理用药的重要参考,该院头孢哌酮/舒巴坦和哌拉西林/他唑巴坦使用基本合理。

哌拉西林与头孢他啶对小儿肺炎的疗效差异研究

目的本文主要探究哌拉西林和头孢他啶对小儿肺炎的临床疗效的差异。方法选择2021年5月—2022年5月在院治疗的80例小儿肺炎的患者,依据治疗方法分为头孢他啶组、哌拉西林组,每组40例。头孢他啶组除常规治疗外给予头孢他啶抗感染,哌拉西林组除常规治疗外给予哌拉西林抗感染。比较两组小儿肺炎患者的治疗效果、症状消失时间、不良反应。结果哌拉西林组治疗效果优于头孢他啶组,哌拉西林组症状消失时间比头孢他啶组短,哌拉西林组不良反应比头孢他啶组少,两组治疗效果、症状消失时间、不良反应的比较差异有统计学意义(P<0.05)。结论哌拉西林是治疗小儿肺炎较为有效的方法,具有治疗效果好、不良反应少的优点,值得临床推广。

哌拉西林及头孢类药物在肺部感染新生儿中的疗效及对肠道益生菌菌落平衡的影响分析

目的:探讨肺部感染新生儿使用头孢类药物与哌拉西林的治疗效果。方法:选取2021年5月~2022年12月期间本院新生儿科收治86例新生儿肺部感染患儿作为研究对象。使用数字表格法将患儿分为I组(28例)、II组(28例)和III组(30例)。I组使用哌拉西林治疗,II组使用头孢类药物治疗,III组采用联合用药治疗。另纳入30例健康新生儿设为对照组。观察各组疗效、不良反应、益生菌菌群平衡情况。结果:III组治愈率最高为96.67%、其次I组治愈率为92.86%、II组治愈率为89.29%,但三组数据统计学分析,差异无统计学意义(P>0.05)。III组不良反应发生率显著高于I组、II组(P<0.05)。I组发生率为0%,显著低于III组的26.67%(χ^(2)=6.563,P<0.05);II组不良反应发生率为3.57%,显著低于III组的26.67%(χ^(2)=4.262,P<0.05);I组不良反与II组比较无显著差异(P>0.05)。以对照组健康新生儿作为参照,对照组类杆菌、双歧杆菌、乳酸菌等益生菌肠道菌群数均明显高于I组、II组、III组(P<0.05)。而I组与II组类杆菌、双歧杆菌、乳酸菌等益生菌肠道菌群数均明显高于III组(P<0.05),I组类杆菌、双歧杆菌、乳酸菌等益生菌肠道菌群数均明显高于II组(P<0.05)。结论:在肺部感染新生儿治疗中,联合哌拉西林、头孢类药物疗效与单一用药类似,但联合用药会增加肠道不良反应情况,且对肠道益生菌菌落平衡破坏较为严重;而单一用药以哌拉西林对肠道益生菌菌落数平衡影响最轻。

临床药师参与处置哌拉西林他唑巴坦与莫西沙星致三系减少患者的药学实践及体会

目的分析1例患者发生三系减少的可能原因与处置办法,为临床哌拉西林他唑巴坦(TZP)与莫西沙星(MFX)的安全合理使用提供参考。方法临床药师参与了1例使用TZP与MFX后发生三系减少患者的药学会诊与药学监护,综合考虑患者的用药情况和发病过程,对三系减少发生的可能原因进行分析和文献复习,并提出了处置建议。结果临床药师综合考虑患者的用药情况和病程,分析三系减少可能是由TZP与MFX引起的,遂建议停用TZP与MFX,并调整抗感染方案及给予对症处理。结论TZP与MFX存在血液系统的不良反应,临床药师应不断加强学习,在临床开展药学实践工作时发挥自身作用,提供相关药学监护,保障患者用药安全合理。