Interpreting culture and susceptibility data in critical care: perks and pitfalls

Problem – The need for immediate, effective antimicrobial therapy in the critical care patient must be tempered by approaches which simultaneously minimize emergence of antimicrobial resistance. Ideally, therapy will successfully resolve clinical signs of infection, while eradicating infecting pathogens such that the risk of resistance is avoided. Increasing limitations associated with empirical antimicrobial choices direct the need for culture and susceptibility data as a basis of therapy. Even so, such in vitro data should be utilized within its limitations. Objectives – To demonstrate the attributes and limitations of patient and population culture and susceptibility (pharmacodynamic) data in the selection of antimicrobial drugs and to demonstrate the design of individualized dosing regimens based on integration of pharmacodynamic (PD) and pharmacokinetic (PK) data. Diagnosis – Limitations in culture and susceptibility testing begin with sample collection and continue through drug selection and dose design. Among the challenges in interpretation is discrimination between pathogens and commensals. Properly collected samples are critical for generation of data relevant to the patient's infection. Data are presented as minimum inhibitory concentrations (MICs). The MIC facilitate selection of the most appropriate drug, particularly when considered in the context of antimicrobial concentrations achieved in the patient at a chosen dose. Integration of MIC data with key PK data yields the C_max:MIC important to efficacy of concentration‐dependent drugs and T>MIC, which guides use of time‐dependent drugs. These indices are then used to design dosing regimens that are more likely to kill all infecting pathogens. In the absence of patient MIC data, population data (eg, MIC₉₀) may serve as a reasonable surrogate. Conclusions – Properly collected, performed, and interpreted culture and susceptibility data are increasingly important in the selection of and design of dosing regimens for antimicrobial drugs. Integration of PK and PD data as modified by host and microbial factors supports a hit hard, exit fast approach to therapy that will facilitate efficacy while minimizing resistance.     

色氨酸对5～10周龄扬州鹅生长性能和屠宰性能的影响

选用270只21日龄的扬州公鹅,随机分成6组,每组3个重复,每个重复15只鹅。采用2×3二因子试验设计,采用两种饲喂方式(自由采食和90%限制饲喂,限制饲喂组鹅饲料供给量为前一天自由采食组饲料消耗量的90%)和低、中、高3个色氨酸(Trp)水平(含量分别为0.14%,0.22%和0.30%),分别对3个不同生长阶段的生长性能和屠宰性能指标进行测定。结果表明,在28～42日龄,与低、高Trp组相比,中Trp组扬州鹅平均日采食量和平均日增重显著提高(P<0.05),饲喂方式和Trp水平对扬州鹅平均日采食量、平均日增重和饲料转化率有交互作用(P<0.05);在42～56日龄,自由采食组扬州鹅平均日采食量和饲料转化率极显著高于限制饲喂组(P<0.01),平均日增重显著高于限制饲喂组(P<0.05)。与低、高Trp组相比,中Trp组扬州鹅平均日采食量显著提高(P<0.05),Trp水平对平均日增重和饲料转化率无显著影响(P>0.05),饲喂方式和Trp水平对扬州鹅平均日采食量有交互作用(P<0.05);在56～70日龄,Trp水平对扬州鹅平均日采食量、平均日增重和饲料转化率均无显著影响(P>0.05)。饲喂方式和Trp水平对扬州鹅平均日增重和饲料转化率有交互作用(P<0.05);在28～70日龄,自由采食组扬州鹅平均日采食量和平均日增重极显著高于限制饲喂组(P<0.01)。与低、高Trp组相比,中Trp组扬州鹅平均日采食量和平均日增重显著提高(P<0.05),而Trp水平对饲料转化率无显著影响(P>0.05),饲喂方式和Trp水平对扬州鹅平均日采食量和平均日增重有交互作用(P<0.05)。自由采食组扬州鹅全净膛率、胸肌率和腹脂率显著高于限制饲喂组(P<0.01),随着Trp水平的增加,扬州鹅胸肌率显著增加(P<0.01),而Trp水平对其他屠宰性能指标无显著影响(P>0.05),饲喂方式和Trp水平对扬州鹅腹脂率有交互作用(P<0.01)。由此可知,饲粮中Trp水平过低或过高均会对扬州鹅生长性能产生不利影响,并且这种不利的影响具有阶段性,因此日粮添加适当水平的Trp能够一定程度改善扬州鹅生长性能。     

基于时-频域指标的控制系统演化校正

“道教文化养生”就是一切有益于健康生活的文化资源向道教养生理论与实践技术转化的综合形态。作为一种学说与实践技术，道教文化养生的形成与发展与道教组织形态同步。将近五千年来，道教先后经历了三大形态：元初道教、古典道教、制度道教。这三大形态的道教都充分运用传统文化资源，建构养生理论，开展养生实践。其代表性的养生体式有：斋醮养生、金丹养生、伦理养生、治世养生、文艺养生、环境养生。     

中国茶道中的道家理念研究

中国茶道源远流长,博大精深。它蕴涵着深刻的宗教文化基础。本文主要探讨了中国茶道与道家思想理念深厚悠远的渊源关系。道家学说为中国茶道注入了“天人合一”的哲学思想,并把崇尚自然,崇尚朴素,崇尚真的美学理念以及贵人、重生、保生尽年的理念贯彻其中,树立了茶道的灵魂,为中华茶文化乃至中华文化作出了重大贡献。     

中西医结合治疗晚期结肠癌的临床疗效

目的 探讨中西医结合治疗晚期结肠癌的临床疗效及生活质量研究。方法 选取在本院住院治疗的经病理检查确诊的晚期结肠癌患者73例,根据治疗方案随机分为中西医结合组（n=38）接受扶正消积汤联合XELOX方案（卡培他滨+奥沙利铂）治疗和西医组（n=35）单纯接受XELOX方案治疗,比较两组患者治疗后近期疗效、治疗前后中医症状积分、肿瘤标志物、免疫细胞水平以及生活质量的差异。结果 中西医结合组总的中医症状积分高于西医组（P<0.05）;中西医结合组治疗后的癌胚抗原（CEA）低于西医组和治疗前（P<0.05）;中西医结合组治疗后的CD4⁺、CD8⁺高于西医组（P<0.05）,与治疗前比无差异（P>0.05）。结论 中西医结合治疗晚期结肠癌的近期疗效,降低中医症状积分,提高生活质量方面均好于单独西医治疗,且对免疫系统的影响较小。     

Pharmacokinetics and Dosage Regimen of Ceftriaxone in Buffalo Calves

The pharmacokinetics and dosage regimen of ceftriaxone were investigated in buffalo calves (n = 6) following a single intravenous administration of ceftriaxone (10 mg/kg). The elimination rate constant was 0.18 +/- 0.01 h(-1) and the elimination half-life was 3.79 +/- 0.09 h. The apparent volume of distribution (Vd(area)) was 1.40 +/- 0.01 L/kg and the total plasma clearance was 0.26 +/- 0.01 L/(kg h). Approximately 43% of total administered dose of ceftriaxone was excreted in urine within 8 h. To maintain a minimum therapeutic concentration of 1 microg/ml, a satisfactory intravenous dosage regimen of ceftriaxone in buffalo calves is 13 mg/kg repeated at 12 h intervals.     

Use of Body Surface Area to Calculate Chemotherapeutic Drug Dose in Dogs: II. Limitations Imposed by Pharmacokinetic Factors

Anticancer drug dosages that specify the maximum dose and minimum dosing interval that are tolerated in a population of dogs are commonly recommended. Because the differences between the effective and toxic doses of most cancer chemotherapeutics is slight, it is important to achieve therapeutic concentrations in tumor tissues at the same time that concentrations in nontarget tissues are minimized. In order to determine the dosage regimen that will most likely accomplish these goals, similar drug concentrations must be achieved in all patients dosed according to a specific regimen. Dosing based on body surface area (BSA) is generally used in an effort to normalize drug concentrations. This is because it is well recognized that measures of many physiologic parameters that are responsible for drug disposition, including renal function and energy expenditure, can be normalized by use of BSA. However, there is substantial evidence that drug disposition is not always proportional to BSA. Differences in distribution, metabolism, and excretion pathways may preclude dose extrapolation among species or among individuals within a species based on BSA. Moreover, genetic differences in drug metabolism are well recognized in humans and in laboratory animals, and it is likely that similar differences exist among breeds of dogs. A review of the pharmacokinetic disposition of several cancer chemotherapeutics suggests that studies are needed to determine the most effective method to achieve equivalent anticancer drug concentrations in diverse veterinary patients.     

Some Pharmacokinetic Parameters and Dosage Regimens for a Long-Acting Formulation of Oxytetracycline in 6- to 8-Month-Old Male Calves

A two-way crossover study was conducted in crossbred male calves (6–8 months old) to determine the bioavailability, pharmacokinetics and dosage regimens for a long-acting formulation of oxytetracycline (OTC-LA). The half-lives of oxytetracycline after intravenous and intramuscular administration were 7.8 h and 24 h, respectively. The volume of distribution and total body clearance values of the drug were 0.86±0.07 L and 76.1±3.3 (ml/h)/kg, respectively. The maximum concentration of the drug in the serum (4.7–7.4 g/ml) was achieved 8–10 h after intramuscular administration. The minimum therapeutic serum concentration of drug of 0.5 g/ml was maintained between 15 min and 84 h after intramuscular administration. The intramuscular bioavailability of the drug was 89.1±4.2%. The dosage regimens to maintain the minimum therapeutic serum concentrations of OTC following intramuscular administration of OTC-LA were computed.     

Pharmacokinetic model of florfenicol in turbot (Scophthalmus maximus): establishment of optimal dosage and administration in medicated feed

The pharmacokinetics of florfenicol (FF) in turbot (Scophthalmus maximus) was studied after single intravenous (10 mg kg⁻¹) and oral (100 mg kg⁻¹) administration. The plasma concentration–time data of florfenicol were described by an open one‐compartment model. The elimination half‐life (t_1/2) was estimated to be 21.0 h, and the total body clearance, Cl, was determined as 0.028 L kg h⁻¹. The apparent volume distribution (V_d) was calculated to be 0.86 L kg⁻¹ and the mean residence time (MRT_iv) was 30.2 h. Following oral administration, the maximum plasma concentration (C_max) of 55.4 μg mL⁻¹ was reached at 12 h (T_max). The absorption constant (k_a) was 0.158 h⁻¹. The bioavailability was estimated to be 57.1%. The low bioavailability observed at higher doses was explained by the saturation of the mechanisms of absorption. The drug absorption process was limited by its inherent low solubility, which limited the amount of available FF absorbed in the gastrointestinal tract. Based on the pharmacokinetic data, an optimal dosing schedule for FF administration is hereby provided. Based on the minimum inhibitory concentration found for susceptible strains of Aeromonas salmonicida, oral FF administration of first, an initial dose of 30 mg FF kg⁻¹, followed by 6 maintenance doses at 18 mg kg⁻¹/daily could be effective against furunculosis in turbot.