住院患者使用头孢三代抗菌药物治疗的合理性研究

目的：探讨住院患者使用头孢三代抗菌药物治疗的合理性。方法选取2012年12月15～21日恩施土家族苗族自治州中心医院使用5种常用头孢三代抗菌药物的住院患者临床资料290例,对住院患者使用头孢三代抗菌药物治疗的合理性进行分析。结果用药居前5位的头孢三代抗菌药物依次为头孢哌酮／他唑巴坦（凯斯）43支、氟氧头孢（氟吗宁）28支、头孢哌酮／他唑巴坦（凯舒特）27支、头孢匹胺（希柏澳）8支、头孢哌酮／他唑巴坦（仙必他）6支;5种头孢三代抗菌药物中,大多数为每日用药2次,其次为每日用药4次和1次,有3例（1．03％）患者存在每日用药1次的用药频率不足的情况;290例患者中233例（80．34％）患者在规定剂量范围内用药,57例（19．66％）患者在规定剂量外用药,且均为超剂量用药;290例患者中应用抗菌药物超过10 d者67例,且连续用药最长时间高达21 d。结论抗菌药物应用中存在给药次数、给药频率、给药剂量与β‐内酰胺类抗菌药物药代动力学及药效动力学规律不相符的情况,需进一步加强合理用药的相关教育和培训。     

外科围手术期患者预防性应用抗菌药物分析

目的了解外科围手术期预防性使用抗菌药物现状,评估其用药合理性。方法随机抽取2009年1-12月265例外科手术患者病历,根据《抗菌药物临床应用指导原则》和《卫生部办公厅关于抗菌药物临床应用管理有关问题的通知》对抗菌药物使用进行合理性评价。结果 265例外科手术患者均使用了抗菌药物,使用率为100%,外科围手术期预防用抗菌药物不合理率为63.89%,存在的主要问题是用药指征过宽、起点过高、手术前预防用药时间不当、术后预防用药时间过长及盲目联合用药。结论外科围手术期抗菌药物预防性使用不合理现象突出,应积极开展合理使用抗菌药物培训,加强抗菌药物使用管理,规范围手术期抗菌药物的使用,从而提高外科围手术期抗菌药物使用合理性。     

神经外科患者围手术期抗菌药物应用时间的调查分析

目的探讨神经外科患者围手术期预防性使用抗菌药物的时间分布,评价其合理性。方法抽取2013年1月至2015年1月8家医院神经外科手术患者共2 400例,其中三级甲等医院4家、二级甲等医院4家,自行设计《抗菌药物应用时间调查表》,采集患者病历中应用抗菌药物名称,术前抗菌药物应用时间,术中是否追加抗菌药物,术后停用抗菌药物时间等信息。结果 2 400例神经外科患者中,Ⅰ类切口1 308例,Ⅱ类切口1 092例,抗菌药物预防性使用率为100%,合计使用抗菌药物11类35种,使用例次为6 314例次,557例次(7.74%)患者的使用时间不合理。结论需加强神经外科患者围手术期预防性使用抗菌药物的用药监测,促进合理用药。     

局麻下小手术预防使用抗菌药物情况调查

目的：为使抗菌药物使用更加合理、安全，对局麻下小手术预防使用抗菌药物情况进行调查。方法：制定调查表，调查2006—11／2008—04出院外科小手术患者使用抗菌药物情况。结果：调查346例小手术，使用抗菌药物率96．2％，人均术前用药时间38．5h，人均术后用药时间154．5h，二联用药率13．8％，使用高价格抗菌药物率占23．1％。结论：小手术预防使用抗菌药物率较高、时间较长，存在联合用药及使用高价格抗菌药物等情况，提示医院需采取有效的措施，加强抗菌药物的管理。     

阑尾炎手术患者围手术期预防性应用抗菌药物情况及合理性

目的调查分析阑尾炎手术患者围手术期预防性应用抗菌药物情况,探讨其用药的合理性。方法随机选取2018年4月至2020年1月在我院实施手术治疗的106例阑尾炎患者作为研究对象。统计患者围手术期预防性应用抗菌药物的情况,并了解其用药时间及联合用药情况,分析用药合理性。结果106例阑尾炎手术患者中,97例为预防性用药,占比为91.51%。预防性用药患者所用药物中,头孢呋辛钠用药频率最高,占比为32.52%,其次为左氧氟沙星、甲硝唑、谷氨酸诺氟沙星及替硝唑。65.98%的患者预防性用药的时间为4~7 d。单独应用1种抗生素共计5例(5.15%),两种抗菌药物联合应用共计89例(91.75%),三种药物联合应用共计3例(3.09%)。206例次用药中,用药合理的共计128例次(62.14%),用药不合理的共计78例次(37.86%)。不合理用药的原因中,前五位分别为选药不当、用药时间过长、联合用药不当、剂量过大及用药时机不合理。结论我院阑尾炎手术患者围手术期预防性应用抗菌药物的比例较高,两种药物联合应用占比较高,大多数患者用药合理。围手术期预防性应用抗菌药物不合理的原因主要是选药不当、用药时间过长、联合用药不当等,临床医师需对这些问题加强关注,进一步提高抗菌药物合理用药水平。     

不可忽视合理的给药时间

治疗疾病常离不开药物，影响药物作用的因素有很多，但与护理关系最密切的是给药时间是否合理。笔者对我省32家医院的住院部作了一次肌肉和静脉途径给药时间安排的调查，结果表明：一天用药2次的给药时间安排的合理性最差，每次用药间隔最短是6h，最长为18h。对这种传统的给药时间安排，本文做如下的探讨。1一般资料本组调查我省32家医院，其中省级医院6家，地市级医院13家，县市级医院13家。调查项目是肌肉和静脉途径，每日用药2－4次的给药时间安排。2结果调查结果是二种途径给药时间安排是一致的，具体给药时间安排（附表）。3讨论合理安…     

海外医学文献荟萃

危重患者抗菌药物持续静脉滴注或延长滴注时间：系统综述和meta分析 摘译：本研究对入住ICU危重患者使用以药物代谢动力学为基础的方法行抗菌药物持续静脉滴注或延长静脉滴注时间,并与传统间歇性静脉滴注抗菌药物进行比较,观察包括病死率在内的各种预后变化。     

我院围手术期患者抗菌药物应用情况分析

目的：了解我院围手术期患者抗菌药物应用情况，为促进临床合理用药提供参考。方法：对我院随机抽取的207例围手术期患者抗菌药物应用进行回顾性分析研究。结果：依据《抗菌药物临床应用指导原则》，207例围手术期患者99．5％应用抗菌药物：药物选择起点过高者53．4％；用药间隔不合理者35．4％；用药剂量大者44．7％；用药时机不当和持续时间长者普遍存在；联合应用2种以上抗菌药物者33．3％：无指征联合用药者7．3％：手术部位感染率4．8名。结论：我院围手术期抗菌药物的使用尚存在许多问题，需要加强规范化使用的管理。     

老年患者抗菌药物使用情况调查分析及护理策略

目的 了解老年患者抗菌药物使用状况,为护士对老年患者进行健康宣教、促进老年患者抗菌药物的合理使用提供依据.方法 采用便利抽样方法选取北京市海淀区某社区卫生服务中心就诊的老年患者60例,通过半结构式访谈法了解其最近一次使用抗菌药物的情况,运用内容分析法对访谈内容进行分析.结果 25％的老年患者（15例）无处方自行使用了抗菌药物,将60例老年患者分为自我用药组（15例）和处方用药组（45例）.泌尿系统感染是两组使用抗菌药物的首要原因.46.6％自我用药的老年患者和55.6％处方用药的老年患者在症状消失时即停服抗菌药物,两组中仅有4例会在症状消失后2～3d巩固用药后再停药.结论 社区老年患者中自我使用抗菌药物的用药行为不容忽视,处方用药的老年患者其抗菌药物的用药依从性有待增强,护理人员需要对老年患者进行合理使用抗菌药物的宣教和用药监护.     

围手术期预防使用抗菌药物监测

目的了解我院围手术期预防使用抗菌药物的现状并评价其合理性,促进围手术期合理预防用药。方法采用回顾性分析,统计围手术期预防使用抗菌药物情况,并评价其合理性。结果 270例手术病例中有231例预防使用抗菌药物,68.8%术前用药时间合理,71.0%术中用药合理,较多病例术后用药时间不合理。Ⅰ、Ⅱ、Ⅲ类手术切口类型占67.5%、22.1%、10.4%,围手术期预防使用抗菌药物单一用药占54.1%,两药联用占38.5%,多药联用占7.4%。共涉及20个药品,其中头孢菌素最多,静脉滴注是主要给药途径。结论我院预防使用抗菌药物尚存在某些不合理之处,应加强管理。     

Importance of beta-lactamase inhibitor pharmacokinetics in the pharmacodynamics of inhibitor-drug combinations: studies with piperacillin-tazobactam and piperacillin-sulbactam.

An in vitro pharmacokinetic model was used to study the pharmacodynamics of piperacillin-tazobactam and piperacillin-sulbactam against gram-negative bacilli producing plasmid-encoded beta-lactamases. Logarithmic-phase cultures were exposed to peak antibiotic concentrations observed in human serum after the administration of intravenous doses of 3 g of piperacillin and 0.375 g of tazobactam or 0.5 g of sulbactam. Piperacillin and inhibitor were either dosed simultaneously or piperacillin was dosed sequentially 0.5 h after dosing with the inhibitor. In studies with all four test strains, the pharmacodynamics observed after simultaneous dosing were similar to those observed with the sequential regimen. Since the ratio between piperacillin and tazobactam was in constant fluctuation after sequential dosing, these data suggest that the pharmacodynamics of the piperacillin-inhibitor combinations were not dependent upon maintenance of a critical ratio between the components. Furthermore, when regrowth was observed, the time at which bacterial counts began to increase was similar between the simultaneous and sequential dosing regimens. Since the pharmacokinetics of the inhibitors were the same for all regimens, these data suggest that the length of time that the antibacterial activity was maintained over the dosing interval with these combinations was dictated by the pharmacokinetics of the beta-lactamase inhibitor in the combination. The antibacterial activity of the combination appeared to be lost when the amount of inhibitor available fell below some critical concentration. This critical concentration varied depending upon the type and amount of enzyme produced, as well as the specific inhibitor used. These results indicate that the antibacterial activity of drug-inhibitor combinations, when dosed at their currently recommended ratios, is more dependent on the pharmacokinetics of the inhibitor than on those of the beta-lactam drug.     

New In Vitro Model To Study the Effect of Human Simulated Antibiotic Concentrations on Bacterial Biofilms

A new in vitro pharmacokinetic/pharmacodynamic simulator for bacterial biofilms utilizing flow cell technology and confocal laser scanning microscopy is described. The device has the ability to simulate the changing antibiotic concentrations in humans associated with intravenous dosing on bacterial biofilms grown under continuous culture conditions. The free drug concentrations of a single 2-g meropenem intravenous bolus dose and first-order elimination utilizing a half-life of 0.895 h (elimination rate constant, 0.776 h⁻¹) were simulated. The antibacterial activity of meropenem against biofilms of Pseudomonas aeruginosa PAO1 and three clinical strains isolated from patients with cystic fibrosis was investigated. Additionally, the effect of meropenem on PAO1 biofilms cultured for 24 h versus that on biofilms cultured for 72 h was examined. Using confocal laser scanning microscopy, rapid biofilm killing was observed in the first hour of the dosing interval for all biofilms. However, for PAO1 biofilms cultured for 72 h, only bacterial subpopulations at the periphery of the biofilm were affected, with subpopulations at the substratum remaining viable, even at the conclusion of the dosing interval. The described model is a novel method to investigate antimicrobial killing of bacterial biofilms using human simulated concentrations.     

In vivo characterization of the pharmacodynamics of flucytosine in a neutropenic murine disseminated candidiasis model

In vivo pharmacodynamic parameters have been characterized for a variety of antibacterial agents. These parameters have been studied in correlation with in vivo outcomes in order to determine (i) which dosing parameter is predictive of outcome and (ii) the magnitude of that parameter associated with efficacy. Very little is known of the pharmacodynamics of antifungal agents. We used a neutropenic murine model of disseminated candidiasis to correlate the pharmacodynamic parameters (percentage of time above the MIC, area under the concentration-time curve [AUC]/MIC and peak level/MIC) for flucytosine (5-FC) in vivo with efficacy as measured by organism number in homogenized kidney cultures after 24 h of therapy. The pharmacokinetics of 5-FC in infected mice were linear. Serum half-lives ranged from 0.36 to 0.43 h. Infection was achieved by intravenous inoculation of 10(6) CFU of yeast cells per ml via the lateral tail vein of neutropenic mice. Groups of mice were treated with fourfold escalating total doses of 5-FC ranging from 1.56 to 400 mg/kg of body weight/day divided into one, two, four, or eight doses over 24 h. Increasing doses produced minimal concentration-dependent killing ranging from 0 to 0.9 log(10) CFU/kidneys. 5-FC did, however, produce a dose-dependent suppression of growth after levels in serum had fallen below the MIC. The fungistatic dose increased from 6 to 8 mg/kg with dosing every 3 and 6 h to 70 mg/kg at with dosing every 24 h. Nonlinear regression analysis was used to determine which pharmacodynamic parameter best correlated with efficacy. Time above the MIC was the parameter best predictive of outcome, while AUC/MIC was only slightly less predictive (time above MIC, R(2) = 85%; AUC/MIC, R(2) = 77%; peak level/MIC, R(2) = 53%). Maximal efficacy was observed when levels exceeded the MIC for only 20 to 25% of the dosing interval. If one considers drug kinetics in humans, these results suggest reevaluation of current dosing regimens.     

替吉奥联合奥沙利铂治疗进展期胃癌临床研究

目的 以FOLFOX6化疗方案为对照组,评估替吉奥联合奥沙利铂方案治疗进展期胃癌的临床疗效及不良反应.方法 70例进展期胃癌患者分成2组,试验组采用替吉奥胶囊80mg· （m2）-1 ·d-1,分2次口服,d1 ～ 14;奥沙利铂130 mg/m2静脉滴注,d1.服药2周停药1周为一疗程.对照组采用奥沙利铂100 mg/m2静脉滴注,d1;亚叶酸钙200 mg/m2静脉滴注,d1;5-氟尿嘧啶400 mg/m2静脉注射,d1;5-氟尿嘧啶2400 mg/m2持续静注不少于46h.每14 d为一疗程.每例患者至少完成2个疗程方能进行评估.疗效评价遵循RECIST1.1标准,不良反应评价遵循NCI-CTC标准.结果 替吉奥联合奥沙利铂治疗进展期胃癌的有效率为57.14％、对照组为48.57％,患者临床收益率试验组为88.57％、对照组为85.71％,两组间比较差异均无统计学意义（P＞0.05）.两组患者出现主要不良反应及严重不良反应（Ⅲ～Ⅳ度）均为恶心及血液学毒性表现,试验组恶心的重度发生率（2.86％）明显低于对照组（25.7％）,差异显著（P＜0.05）.而组间其他不良反应比较无显著差异（P＞0.05）.结论 替吉奥联合奥沙利铂方案治疗进展期胃癌的近期疗效较好,不良反应发生较轻,尤其减少了恶心发生的概率并减轻了化疗引起的恶心程度,值得临床上进一步研究应用.     

Single-dose pharmacokinetics and safety of a novel broad-spectrum cephalosporin (BAL5788) in healthy volunteers

BAL5788 is the water-soluble prodrug of BAL9141, a novel broad-spectrum cephalosporin with potent bactericidal activities against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. We investigated the safety and pharmacokinetics of BAL5788 in a double-blind, single-ascending-dose study with 40 healthy male subjects. The subjects were randomized to receive placebo (n = 2 subjects per dose) or BAL5788 (n = 6 subjects per dose) as a 200-ml intravenous infusion over 30 min. The BAL5788 doses used were 125, 250, 500, 750, and 1,000 mg (BAL9141 equivalents). All doses were well tolerated, with no severe or serious adverse events (AEs). The most frequent AE was taste disturbance. No electrocardiographic abnormalities and no trends or clinically significant changes in laboratory parameters or vital signs were observed. The maximum concentration of drug in serum and the area under the concentration-time curve for BAL9141 were dose proportional over the dosing range. The elimination half-life of BAL9141 was about 3 h. The volume of distribution at steady state was equal to the volume of the adult extracellular water compartment, and the rate of renal clearance of free drug corresponded to the normal glomerular filtration rate for adults. More than 70% of the administered dose was excreted as BAL9141 in the urine, and almost no prodrug was detected. After the infusion of 750 mg, the mean plasma BAL9141 concentrations exceeded the MIC at which 100% of MRSA isolates are inhibited (4 microg/ml) for approximately 7 h, or 58% of a 12-h dosing interval. These results indicate that infusions of 750 mg twice a day should be adequate for the treatment of infections caused by MRSA.     

Effects of metronidazole, tetracycline, and bismuth-metronidazole-tetracycline triple therapy in the Helicobacter pylori SS1 mouse model after 1 day of dosing: development of an H. pylori lead selection model

We evaluated the effect of optimized doses and dosing schedules of metronidazole, tetracycline, and bismuth-metronidazole-tetracycline (BMT) triple therapy with only 1 day of dosing on Helicobacter pylori SS1 titers in a mouse model. A reduction of bacterial titers was observable with 22.5 and 112.5 mg of metronidazole per kg of body weight (as well as BMT) given twice daily and four times daily (QID). Two hundred milligrams of tetracycline per kilogram, given QID, resulted in only a slight reduction of H. pylori titers in the stomach. We argue that optimization of doses based on antimicrobial drug levels in the animal and shortened (1 or 2 days) drug administration can be used to facilitate early evaluation of putative anti-H. pylori drug candidates in lieu of using human doses and extended schedules (7 to 14 days), as can be deduced from the results seen with these antimicrobial agents.     

Importance of the mode of intravenous administration on cephotaxime concentration in bile. A comparison of bolus, drip infusion and bolus plus drip infusion

Success of antibacterial therapy depends on many factors, among which the level reached at the site of infection is important. Drug concentration in tissues and body fluids can be related to the mode of administration. The aim of the present work was to study the levels of cephotaxime (CFX) in bile, after intravenous administration of 1 g by bolus, drip infusion and bolus plus drip infusion. The drug was detected by a microbiological method. The results indicate that passage of CFX from blood into bile is a carrier-mediated process, and bolus, in the case of CFX, is the best mode of administration.     

大剂量甲基泼尼松龙冲击疗法治疗视神经脊髓炎21例

目的观察大剂量甲基泼尼松龙冲击治疗视神经脊髓炎（NMO）急性发作病例的临床疗效。方法对21例临床确诊为NMO急性发作的患者以甲基泼尼松龙1000mg／d，静脉滴注3d；随后以甲基泼尼松龙一日80mg，静脉滴注3d；随后改用泼尼松片剂口服，在一个月内逐渐减量直至停药。采用Barthel指数对入院第3天和治疗后第15天的日常生活能力进行评价，采用近视力表对治疗前后的视力进行比较。结果21例患者经治疗后，17例疗效显著，占80．9％；4例无效。人院第3天与治疗后第15天的Barthel指数总评分相比有显著差异。所有病例治疗后视力显著改善。结论大剂量甲基泼尼松龙冲击疗法对NMO急性发作治疗有效。     

Effect of GrlA mutation on the development of quinolone resistance in Staphylococcus aureus in an in vitro pharmacokinetic model

OBJECTIVES: To investigate the effect of GrlA mutation on the development of quinolone resistance in Staphylococcus aureus in an in vitro pharmacokinetic (PK) model and to examine the relationship between the emergence of resistance and PK/pharmacodynamic parameters. METHODS: A wild-type and a GrlA mutant of S. aureus were exposed to the Japanese clinical dose of ciprofloxacin in an in vitro PK model, and the development of resistance was measured by population analysis. In addition, several doses of four quinolones (pazufloxacin, ciprofloxacin, levofloxacin and tosufloxacin) were tested against the GrlA mutant. All model simulations were single-dose design and were conducted over 24 h. RESULTS: Four quinolones were tested against the GrlA mutant, and a resistant population emerged after treatment with 250 mg pazufloxacin intravenous drip infusion, 600 mg ciprofloxacin intravenous drip infusion, 200 mg levofloxacin oral dosing and 150 mg tosufloxacin oral dosing. The emergence of a resistant population was not induced by treatment with 500 mg pazufloxacin intravenous drip infusion, 2,400 mg ciprofloxacin intravenous drip infusion, 400 mg levofloxacin oral dosing and 600 mg tosufloxacin oral dosing. Treatment with the clinical dose of ciprofloxacin induced the development of resistance in the GrlA mutant, but not in the wild-type strain. CONCLUSIONS: These data suggest that the frequency of acquisition of additional mutations differs between the wild-type and the GrlA mutant of S. aureus. Also, GrlA mutation predisposes S. aureus to develop high-level quinolone resistance.     

Interaction between metronidazole and drugs eliminated by oxidative metabolism

Single-dose kinetics of 0.1 mg/kg intravenous diazepam, 10 mg/kg oral antipyrine, and 300 mg oral phenytoin were followed in healthy subjects before and after 400 mg metronidazole twice a day for 5 days. When data before metronidazole dosing were compared with those after metronidazole dosing, there were no changes in total plasma clearance of diazepam (0.53 and 0.65 ml/min/kg), antipyrine (39.0 and 38.0 ml/min/kg), or phenytoin (0.56 and 0.55 ml/min/kg). Plasma t 1/2s and volumes of distribution of the three drugs tested were not affected by metronidazole, but urinary excretion of 4-hydroxyantipyrine decreased after metronidazole dosing. There was no change in the elimination of phenytoin as its hydroxylated metabolite after metronidazole. It is concluded that, at therapeutic concentrations, metronidazole does not significantly inhibit oxidative drug metabolism.