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.

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.

Construction of universal quantitative models for the determination of cefoperazone sodium/sulbactam sodium for injection from different manufacturers using near-infrared reflectance spectroscopy

To develop near-infrared （NIR） reflectance spectroscopic methods for the quantitative analysis of cefoperazone sodium/ sulbactam sodium from different manufacturers for injection powder medicaments. Various powders of cefoperazone sodium/ sulbactam sodium were directly analyzed by non-destructive NIR reflectance spectroscopy using the spectrometer EQUINOX55. Two quantitative methods via integrating sphere （IS） and fiberoptic probe （FOP） models were explored from 6 batches of commercial samples and 42 batches of laboratory samples at a content ranging from 30% to 70% for cefoperazone and 60% to 20% for sulbactam. The root mean square errors of cross validation （RMSECV） and the root mean square errors of prediction （RMSEP） of IS were 1.79% and 2.85%, respectively, for cefoperazone sodium, and were 1.86% and 3.08%, respectively, for sulbactam sodium; and those of FOP were 2.93% and 2.92%, respectively, for cefoperazone sodium, and were 2.23% and 3.01%, respectively, for sulbactam sodium. Based on the ICH guidelines and Ref. 12, the quantitative models were then evaluated in terms of specificity, linearity, accuracy, precision, robustness and model transferability. The non-destructive quantitative NIR methods used in this study are applicable for rapid analysis of injectable powdered drugs from different manufacturers.

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.

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.

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.

Sclerotherapy with Leuprolide and Cefoperazone Sulbactam in the Management of Ovarian Endometriomas under Ultrasound Guidance: A Novel Approach

Endometriosis is an estrogen dependent gynecological disorder, which can occur throughout the reproductive age of women, causing chronic pelvic pain, substantial morbidity, and impaired fertility. It is clinically defined as the presence of ectopic endometrium resulting in sustained inflammatory reaction. In India, about 29,000,000 women suffer from endometriosis. Severe pelvic pain and recurrent endometriomas were observed even after surgery. We have conducted aspirations totally in 110 patients in which most of the patients were suffering from Stage III & Stage IV of endometriosis except for 7 patients for whom we have done as primary therapy for endometriomas. Among 110 patients, 4 patients didn’t turn up for follow up after first aspiration. This pilot study conducted with 110 patients in Ponni Hospital and Fertility Research Centre, Madurai aimed to evaluate pregnancy outcome in 51 infertile patients, and to alleviate pelvic pain, to restore a healthy sexual life and to reduce the recurrence rate of Ovarian Endometriomas (OE) in 59 patients, who did not seek fertility, After using the newer sclerosing agent Leuprolide with Cefoperazone Sulbactam (LCS) under ultrasound guidance. This prospective pilot study resulted in a highly significant achievement in pregnancy where 41 patients conceived out of 51 patients (80.39%) only 6 are in ongoing treatment. Those who didn’t seek fertility were 59 of which 43 have completed family 13 have one child and 3 unmarried girls. 96.61% were relieved of pain and recurrence and restored healthy sexual life, 2 are in ongoing treatment. We have not encountered any adverse effects during this treatment.

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.

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).

阿奇霉素联合头孢哌酮舒巴坦治疗小儿细菌性肺炎的效果分析

目的:分析阿奇霉素联合头孢哌酮舒巴坦治疗小儿细菌性肺炎的效果。方法:选取2017年2月—2023年2月北京丰台医院收治的66例细菌性肺炎患儿作为研究对象,根据随机数字表法分为观察组和对照组,各33例。两组均给予常规治疗,对照组在常规治疗基础上给予头孢哌酮舒巴坦治疗,观察组在对照组基础上给予阿奇霉素治疗。比较两组症状体征持续时间、胸部CT病灶持续时间、住院时间、D-二聚体(D-D)水平和炎性因子水平。结果:观察组发热持续时间、喘息持续时间、咳嗽持续时间、肺部啰音持续时间、胸部CT病灶持续时间及住院时间短于对照组,差异有统计学意义(P<0.001)。治疗前,两组D-D、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)水平比较,差异无统计学意义(P>0.05);治疗后,两组D-D、TNF-α、IL-6、IL-8水平低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05)。结论:阿奇霉素联合头孢哌酮舒巴坦治疗小儿细菌性肺炎的效果较好,可加速缓解症状,减轻炎性反应,促进康复。

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。

Study on the Effect of Shuanghuanglian Powder Needle Combined with Cefoperazone and Sulbactam Sodium on Pseudomonas aeruginosa in Vitro

Objective: To explore the antibacterial activity of combined use of Shuanghuanglian and cefoperazone sulbactam sodium on resistant strains of Pseudomonas aeruginosa. Methods: The Pseudomonas aeruginosa strains which were sensitive and resistant to cefoperazone sulbactam sodium were selected to prepare different test bacterial solutions respectively;The experimental liquid of Shuanghuanglian and Cefoperazone Sulbactam Sodium were prepared separately and set as different test groups and control groups;The Drug Sensitivity Tests of Shuanghuanglian and cefoperazone sulbactam sodium at different concentration gradients which were used alone or used in combination were carried out for different strains with sensitivity and resistance, And use standard entry as a reference control. Result: The results of drug sensitivity test of Shuanghuanglian combined with Cefoperazone-Sulbactam sodium against the resistant strains of Pseudomonas aeruginosa were compared with the results of drug sensitivity test of the two separately used, and the difference was statistically significant (P 〈 0.05) [The drug sensitivity test results of Shuanghuanglian and cefoperazone sulbactam sodium to Pseudomonas aeruginosa resistant strains were statistically significant compared with the drug sensitivity test results of Shuanghuanglian and Cefoperazone Sulbactam Sodium used separately (P 〈 0.05)];There was a dependence between strains and concentration in the effect of the combination of the two drugs. Conclusion: The combination of Shuanghuanglian and cefoperazone sulbactam sodium has synergistic antibacterial or bactericidal effect on Pseudomonas aeruginosa resistant strains. .

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.

The Study of Effect of Commercial Baicalin Combined with Cefoperazone Sulbactam Sodium on Pseudomonas aeruginosa in Vitro

Objective: To investigate the antibacterial effect of baicalin combined with cefoperazone-sulbactam sodium on drug-resistant strains of Pseudomonas aeruginosa. Method: Pseudomonas aeruginosa strains that are sensitive and resistant to cefoperazone-sulbactam sodium were selected to prepare different test bacterial solutions respectively;The test solutions of baicalin and cefoperazone sulbactam sodium were prepared respectively, and different test groups and control groups were set up;The drug sensitivity tests of different concentration gradients of baicalin and cefoperazone sulbactam sodium used alone and in combination were carried out for different sensitive and drug-resistant strains, and the standard strains were used as parallel control. Result: The drug susceptibility test results of the combined use of baicalin and cefoperazone-sulbactam against Pseudomonas aeruginosa drug-resistant strains were compared with the drug susceptibility results of the two used separately, and the difference was statistically significant (P Pseudomonas aeruginosa.

头孢哌酮钠舒巴坦钠致凝血功能异常的危险因素分析

目的 探讨头孢哌酮钠舒巴坦钠致凝血功能异常的危险因素分析。方法 收集经第三代头孢菌素抗生素(头孢哌酮钠舒巴坦钠)治疗的100例患者为研究对象。根据患者是否出现凝血功能异常分为异常组(n=29)和正常组(n=71)。比较2组性别、年龄、体温、脉搏、治疗疗程、白细胞计数(white cell count,WBC)、白蛋白、尿素氮、总胆红素(total bilirubin,TBIL)、降钙素原(procalcitonin,PCT)、C反应蛋白(C-reactive protein,CRP)、饮食情况、用药剂量、合并基础病等;通过多因素Logistic回归分析明确患者凝血功能异常的危险因素;通过Person系数分析WBC、白蛋白、尿素氮、CRP与凝血酶原时间(prothrombin time,PT)、活化部分凝血酶原时间(activated partial prothrombin time,APTT)的相关性。结果 2组性别、年龄、体温、脉搏、治疗疗程、TBIL、PCT、CRP、合并高血压、合并糖尿病比较差异无统计学意义(P>0.05);异常组白蛋白水平显著低于正常组,WBC、尿素氮、CRP水平、饮食<1 200 mL/d、用药剂量≥3 g/d占比均高于正常组(P<0.05);经ROC分析证实WBC、白蛋白、尿素氮、CPR水平均可用于头孢哌酮钠舒巴坦钠在抗感染过程中凝血功能异常的预测,曲线下面积分别为0.913、0.829、0.920、0.847(P<0.05);经多因素Logistic回归分析证实,饮食<1 200 mL/d、用药剂量≥3 g/d、WBC>11.385×10~9/L、白蛋白<28.815 g/L、尿素氮>14.199μmol/L、CRP>17.629 mg/L是凝血功能异常的危险因素(P<0.05);相关性分析显示,WBC、尿素氮、CPR水平与PT、APTT均呈正相关,白蛋白与PT、APTT呈负相关(P<0.05)。结论 头孢哌酮钠舒巴坦钠在抗感染过程中致凝血功能异常受到诸多因素影响,如较高的WBC、尿素氮、CPR水平,较低的白蛋白水平,较高的用药剂量,较少的饮食等,WBC、尿素氮、CPR水平越高及白蛋白水平越低,患者凝血功能越差。

头孢哌酮/舒巴坦致血小板减少列线图预测模型的建立与验证

目的探讨头孢哌酮/舒巴坦致成人住院患者血小板减少的预测因子,建立列线图预测模型并进行验证。方法回顾性收集西安市中心医院2021年6月30日至2023年6月30日使用头孢哌酮/舒巴坦治疗的成人住院患者资料,按7∶3随机分为训练集和内部验证集。采用单因素/多因素Logistic回归分析筛选头孢哌酮/舒巴坦致血小板减少的独立预测因子,通过R4.0.3软件“RMS”包绘制列线图;采用受试者工作特征曲线及C-index值评估模型的预测效能;采用Hosmer-Lemeshow拟合优度检验评价模型的校正度。以相同标准,收集西安市第一医院同期使用头孢哌酮/舒巴坦治疗的成人住院患者的临床资料,对列线图预测模型进行外部验证。结果共纳入西安市中心医院患者1045例,其中头孢哌酮/舒巴坦致血小板减少患者67例,发生率为6.41%。排除假阳性患者后,最终纳入患者473例,其中训练集331例、内部验证集142例。多因素Logistic回归分析结果显示,患者年龄[OR=1.043,95%CI(1.017,1.070)]、估算的肾小球滤过率(eGFR)[OR=0.988,95%CI(0.977,0.998)]、基线血小板[OR=0.989,95%CI(0.982,0.996)]、营养风险[OR=3.863,95%CI(1.884,7.921)]和累计限定日剂量数(DDDs)[OR=1.082,95%CI(1.020,1.147)]是头孢哌酮/舒巴坦致血小板减少的独立预测因子(P<0.05)。训练集和内部验证集的C-index值分别为0.824[95%CI(0.759,0.890)]和0.828[95%CI(0.749,0.933)],Hosmer-Lemeshow检验的χ^(2)值分别为0.441、1.804(P值分别为0.802、0.406)。外部验证集中,C-index值为0.808[95%CI(0.672,0.945)],Hosmer-Lemeshow检验的χ^(2)值为0.899(P值为0.638)。结论患者年龄、基线血小板、eGFR、营养风险和累计DDDs是头孢哌酮/舒巴坦致血小板减少的独立预测因子;所建列线图预测模型具有良好的预测效能和外推性,有助于临床快速、准确地识别头孢哌酮/舒巴坦致血小板减少的潜在风险。

哌拉西林-他唑巴坦对急性心肌梗死经皮冠状动脉介入治疗术后医院感染者炎性因子的影响

目的 探究哌拉西林-他唑巴坦对急性心肌梗死经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后医院感染患者炎性因子及心肌酶谱的影响。方法 以80例急性心肌梗死PCI术后医院感染患者作为研究对象,随机分为对照组和观察组,每组40例。对照组给予头孢呋辛,观察组给予哌拉西林-他唑巴坦。比较2组的临床疗效、炎性因子[超敏C反应蛋白(high-sensitivity C-reactive protein,hs-CRP)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)和白细胞介素-6(interleukin-6,IL-6)]、左心室重构[左心室舒张末期内径(left ventricular end-systolic diameter, LVESD)、收缩末期内径(left ventricular end-diastolic diameter, LVEDD)和左心室射血分数(left ventricular ejection fraction, LVEF)]、心肌酶谱指标[肌钙蛋白Ⅰ(cardiac troponin Ⅰ,cTnⅠ)、肌酸激酶同工酶(creatine kinase-MB, CK-MB)和肌酸脱氢酶(lactate dehydrogenase, LDH)]和不良反应。结果 治疗后,与对照组比较,观察组的总有效率明显较高(P<0.05);观察组的hs-CRP、MMP-9和IL-6均明显较低(P<0.05),LVESD、LVEDD均明显较低(P<0.05), LVEF明显较高(P<0.05), cTnⅠ、CK-MB和LDH均明显较低(P<0.05);2组不良反应总发生率比较差异无统计学意义(P>0.05)。结论 哌拉西林-他唑巴坦对急性心肌梗死PCI术后医院感染患者具有较好的临床疗效,可下调炎性因子,减轻左心室重构,降低心肌酶谱指标水平,且安全性高。

基于FAERS的哌拉西林他唑巴坦不良事件信号挖掘与分析

目的挖掘哌拉西林他唑巴坦(TZP)的药品不良事件(ADE)信号,促进临床合理、安全用药。方法采用比例失衡法对美国食品药品管理局不良事件报告系统(FAERS)自建库至2024年3月所有TZP ADE报告进行信号挖掘,分析报告病例的基本情况及不良反应相关信息。结果共提取得到主要怀疑药物涉及ADE报告数为20620513条,TZP为主要怀疑药物涉及ADE报告数为6489条。共挖掘ADE信号543个,涉及25个器官/系统分类(SOC),二次筛选最终检测出ADE信号数43个,其中新的ADE信号17个,ADE信号涉及SOC分类的数量排名前5为分别是皮肤及皮下组织类疾病、全身性疾病及给药部位各种反应、各类检查、感染及侵染类疾病、血液及淋巴系统疾病;ADE信号数排名前5位的首选术语分别为皮疹、发热、急性肾损伤、瘙痒、血小板减少症。青霉素类药物在血液及淋巴系统疾病存在多种不良反应信号,TZP导致血小板减少病例数最多,苯唑西林导致粒细胞缺乏关联强度比例报告比值比最高;TZP导致白细胞减少疗程中位数为11.00 d,累积剂量中位数为148.50 g;该药导致粒细胞缺乏疗程中位数为14.00 d,累积剂量中位数为216.00 g;该药导致血小板减少症疗程中位数为7.00d,累积剂量中位数为87.00 g。结论用药期间需密切关注皮肤及皮下组织类疾病相关不良反应,可能较胃肠道系统疾病更多;临床大剂量或长疗程应用TZP时可导致多个系统发生不良反应,尤其需密切关注血液及淋巴系统疾病相关不良反应,避免发生严重不良反应。