两种抗生素骨水泥物理和力学性能及洗提特性的实验研究

目的探讨庆大霉素或万古霉素加入骨水泥后，其对骨水泥力学和物理特性的影响及其体外释放情况，用于指导临床应用。方法在40克骨水泥中分别加入庆大霉素1g,2g，万古霉素1g、2g。测定各组骨水泥的压缩强度、弯曲模量和弯曲强度，并进行洗提实验。结果40g骨水泥中加入少于2g的抗生素不会对骨水泥的物理和力学性能产生影响，万古霉素的洗提量高于庆大霉素。结论抗生素能够从骨水泥中持续有效的释放；40g骨水泥中加入少于2g抗生素不会影响骨水泥的物理和力学性能；在洗提效果上，万古霉素要好于庆大霉素。     

常用抗生素在体外环境中对血清肿瘤标志物检测的影响

目的探讨十一种常用抗生素在体外环境中对血清肿瘤标志物含量的影响。方法 50份肿瘤患者血清和20份正常血清中分别加入11种常用抗生素,采用免疫化学发光法检测AFP、CEA、CA125、CA153和CA199五种肿瘤标志物前后含量的变化,采用T检验进行统计学分析。结果加入青霉素钠、阿昔洛韦、乳酸环丙沙星氯化钠、头孢他啶、头孢呋辛钠、奥硝唑片、头孢拉啶后AFP检测值有差异(P<0.05);在加入乳酸环丙沙星氯化钠、头孢他啶、头孢呋辛钠、头孢拉啶、阿奇霉素磷酸二氢钠后CEA检测值有差异(P<0.05);在加入阿昔洛韦、头孢呋辛钠、头孢拉啶、亚胺培南西司他丁钠后CA125检测值有差异(P<0.05);在加入青霉素钠、头孢呋辛钠、哌拉西林钠舒巴坦钠(2∶1)、奥硝唑片、阿昔洛韦后CA199检测值有差异(P<0.05);在加入青霉素钠、头孢呋辛钠、哌拉西林钠舒巴坦钠(2∶1)、奥硝唑片、亚胺培南西司他丁钠、头孢他啶后CA153检测值有差异(P<0.05)。结论 11种常用抗生素除硫酸庆大霉素外,绝大多数对肿瘤标志物检测有影响,排除药物干扰因素对提高肿瘤标志物检测准确性具有临床意义。     

两种抗生素复合骨水泥体外药物释放的规律

目的:观察抗生素复合骨水泥体外释药规律,以及有效的检测方法。方法:实验于2005-10/2006-01在解放军第四二五医院外二科完成。将骨水泥固体相分别与万古霉素和庆大霉素按照1∶25(g∶mg)的比例混合,再按2g∶10mL∶50mg(固相:液相:抗生素)比例加入骨水泥液相,搅拌成糊状,注入模具中铸型,采用K-B制片扩散法,对两种抗生素各浓度梯度的抑菌环直径平均值与药物浓度之间的关系进行相关分析。以金黄色葡萄球菌为敏感细菌,检测1,3,5,7,10,14,22,26,30d9个时间点抗生素骨水泥制件浸泡液,观察骨水泥中抗生素的释放效果,并根据结果绘制释药曲线,计算释药效率。结果:①万古霉素浓度-抑菌环直径标准方程Y=2.71 5.59X(r=0.989),庆大霉素浓度-抑菌环直径Y=0.17 7.87X(r=0.977)。②骨水泥早期爆发释药,中期平稳释药,26d释药浓度大于对应细菌最低抑菌浓度。骨水泥释药复合Higuchi方程。30d抗生素释放率分别是83.73%和89.38%。结论:①骨水泥具有缓释模型特点,为感染性人工髋关节翻修术中的应用提供实验依据。②K-B法可简单有效检测抗生素骨水泥的释药效果。     

两种抗生素复合骨水泥体外药物释放的规律

目的：观察抗生素复合骨水泥体外释药规律，以及有效的检测方法。 方法：实验于2005-10／2006—01在解放军第四二五医院外二科完成。将骨水泥固体相分别与万古霉素和庆大霉素按照1：25（g：mg）的比例混合，再按2g：10mL：50mg（固相：液相：抗生素）比例加入骨水泥液相，搅拌成糊状，注入模具中铸型，采用K—B制片扩散法，对两种抗生素各浓度梯度的抑菌环直径平均值与药物浓度之间的关系进行相关分析。以金黄色葡萄球菌为敏感细菌，检测1，3，5，7，10，14，22，26，30d9个时间点抗生素骨水泥制件浸泡液，观察骨水泥中抗生素的释放效果，并根据结果绘制释药曲线，计算释药效率。 结果：①万古霉素浓度-抑菌环直径标准方程Y=2．71＋5．59X（r=0．989），庆大霉素浓度-抑菌环直径Y=0．17＋7．87X（r=0．977）。②骨水泥早期爆发释药，中期平稳释药，26d释药浓度大于对应细菌最低抑菌浓度。骨水泥释药复合Higuchi方程。30d抗生素释放率分别是83．73％和89．38％。 结论：①骨水泥具有缓释模型特点，为感染性人工髋关节翻修术中的应用提供实验依据。②K—B法可简单有效检测抗生素骨水泥的释药效果。     

乡镇卫生院剖宫产围手术期规范应用抗生素效果分析

目的观察乡镇卫生院剖宫产围手术期规范应用抗生素的效果。方法将符合入选标准的剖宫产孕妇194例分为观察组(98例)和对照组(96例)。观察组于术中断脐后立即予头孢呋辛钠静脉给药,术后每8 h给药1次,共3次。对照组术后回病房予头孢呋辛钠静脉给药,术后每8 h给药1次,共7 d。出院后随访3周,比较2组术后感染率、住院天数、住院费用及抗生素使用费用等指标。结果观察组的术后感染率、平均住院天数、住院费用及抗生素使用费用等指标均优于对照组(P<0.05或P<0.01)。结论规范短疗程头孢呋辛钠预防剖宫产术后感染效果优于传统长疗程头孢呋辛钠,并明显降低平均住院天数、住院费用,可作为乡镇卫生院剖宫产手术预防感染首选方案。     

预防性应用抗生素在产科围手术期中的临床价值研究

将120例产妇随机分为观察组和对照组,观察组手术前后给予头孢呋辛钠静脉滴注,对照组仅在术后予头孢呋辛钠静脉滴注。观察组术后平均最高体温、退热时间、术后病率、切口感染率、不良反应发生率均较对照组低,差异有显著性(P<0.05);人均抗生素用量观察组6.0±1.0g,对照组18.8±5.6g,两组差异有高度显著性(P<0.01)。与仅在术后应用抗生素比较,妇产科围手术期预防性应用抗生素更能达到预防感染的目的。     

抗生素骨水泥与人工关节置换后的翻修

背景：抗生素骨水泥是预防和治疗人工关节置换以及翻修后感染的重要方法。目的：综述抗生素骨水泥的研究进展以及人工关节置换后翻修。方法：通过计算机检索Pubmed数据库、中国知网数据库、中国生物医学文献数据库、维普期刊全文数据库、万方数据库,时间范围在1978年至2012年,中文检索词“骨水泥”、“抗生素骨水泥”、“感染”、“关节置换”;英文检索词“bone cement”、“antibiotic bone cement”、“infection”、“joint replacement”。结果与结论：共检索到相关文献335篇。通过阅读标题、摘要以及全文进行初步筛选,最后保留29篇文献进行深入的分析。抗生素骨水泥目前已广泛应用于人工关节置换以及翻修后感染的治疗,可以降低初次关节置换和翻修后感染的风险。适量的抗生素与骨水泥混合后其材料特性和力学性能不会发生改变。不同抗生素在骨水泥中的释放率也存在不同,与骨水泥的孔隙率有着密切的关系,在骨水泥中加入能够增加孔隙率的添加剂,可以达到最终增加抗生素释放的目的。     

万古霉素骨水泥缓释药物观察及检测方法建立

正万古霉素(vancomycin)为糖肽类抗生素,临床上用于严重革兰氏阳性菌、耐甲氧西林的金葡菌(MRSA)、耐甲氧西林的表皮葡萄球菌(MRSE)所致的感染。1970年,Buchholz等发现抗生素掺入骨水泥中可以形成抗生素缓释系统,并通过浓度梯度向周围长时间持续释放。万古霉素骨水泥在临床人工关节置换等术式的局部抗感染及其应用的实验研究中倍受关注,本文建立了高效液相色谱法检测     

妇产科围术期预防性应用抗生素的临床价值探讨

目的探讨妇产科围术期预防性应用抗生素的临床价值。方法将152例妇产科手术患者随机分为2组,每组76例。观察组于术前30min内静滴头孢呋辛钠1.5 g/次,并于术后6 h重复给药1次;对照组仅于术后静滴头孢呋辛钠1.5 g,2次/d。比较2组患者术后最高体温、退热时间、住院时间、术后感染情况及不良反应的差异。结果对照组患者术后最高体温、退热时间、住院时间及术后感染发生率均显著大于观察组;2组不良反应发生率无显著差异。结论妇产科围术期预防性应用抗生素与仅术后应用抗生素比较,术后最高体温、退热时间、住院时间及术后感染率均得到显著降低或缩短,说明该方法安全可靠,具有较高的临床应用价值,值得推广。     

硫酸庆大霉素注射液与注射用头孢哌酮钠舒巴坦钠存在配伍禁忌

腹膜透析是治疗慢性肾功能不全的有效替代方法之一，腹膜炎是腹膜透析常见的并发症，在治疗腹膜炎的过程中需要在腹透液中加入抗生素，而多种抗生素混合使用时存在配伍禁忌，如硫酸庆大霉素注射液与注射用头孢哌酮钠舒巴坦钠混合可在以下两种情况下立即呈乳白色：（1）硫酸庆大霉素注射液与注射用头孢哌酮钠舒巴坦钠粉剂混合；     

In vitro activities of daptomycin-, vancomycin-, and teicoplanin-loaded polymethylmethacrylate against methicillin-susceptible, methicillin-resistant, and vancomycin-intermediate strains of Staphylococcus aureus

The objective of this study was to evaluate the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with daptomycin, vancomycin, and teicoplanin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-intermediate Staphylococcus aureus (VISA) strains. Standardized cement specimens made from 40 g PMMA loaded with 1 g (low-dose), 4 g (middle-dose) or 8 g (high-dose) antibiotics were tested for elution characteristics and antibacterial activities. The patterns of release of antibiotics from the cement specimens were evaluated using in vitro broth elution assay with high-performance liquid chromatography. The activities of broth elution fluid against different Staphylococcus aureus strains (MSSA, MRSA, and VISA) were then determined. The antibacterial activities of all the tested antibiotics were maintained after being mixed with PMMA. The cements loaded with higher dosages of antibiotics showed longer elution periods. Regardless of the antibiotic loading dose, the teicoplanin-loaded cements showed better elution efficacy and provided longer inhibitory periods against MSSA, MRSA, and VISA than cements loaded with the same dose of vancomycin or daptomycin. Regarding the choice of antibiotics for cement loading in the treatment of Staphylococcus aureus infection, teicoplanin was superior in terms of antibacterial effects.     

Increased release of gentamicin from acrylic bone cements under influence of low-frequency ultrasound.

The release profile of antibiotics from antibiotic-loaded bone cement, used to prevent infections in total joint arthroplasty, is neither ideal nor complete. Ultrasound has been used to allow drugs to cross otherwise impermeable barriers. The aim of this study was to establish a possible effect of ultrasound on antibiotic release from bone cements. Samples were made of three commercially available gentamicin-loaded bone cements. Part of the samples was allowed to release gentamicin for 3 weeks before insonation. An insonation device produced an ultrasound field with a time average acoustic intensity of 167 mW/cm2 at a frequency of 46.5 kHz. The samples were exposed to the ultrasound field or not exposed to it as a control. The amount of gentamicin released was measured by fluorescence polarization immunoassay. There was a limited increase of gentamicin release with application of ultrasound in fresh samples but not in the samples that had been allowed to release gentamicin. For fresh samples, a linear regression model showed that this ultrasound effect was statistically significant. The mechanism behind these observations is not clear, but it is suggested that microstreaming or localized temperature rises may be involved.     

In vitro measurement of the time-related efficacy of gentamicin sulfate release from bone cements

BACKGROUND: The aim of the present study was to establish an in vitro microbiologic monitoring system which measures the dynamics of antibiotic release from acrylic bone cement and its antibacterial efficacy. METHODS: Palacos R and Orthofix R cements containing gentamicin sulfate were tested. The in vitro elution dynamics was analyzed by plate diffusion method during a 1-year period after mixing. High but rapidly decreasing antibiotic levels were detected within the 1st week, resulting in an almost steadily low concentration by the end of the 1st month. After 1 year, it was still possible to demonstrate the inhibitory effect of the drug from both cements. Comparison of the time-related release between the antibiotics failed to find any statistically significant differences. CONCLUSION: The method described is a useful and reproducible technique for the in vitro measurement of the inhibitory activity of antibiotic released from bone cements.     

Release of gentamicin and vancomycin from temporary human hip spacers in two-stage revision of infected arthroplasty

AIM: Evaluation of the delivery of gentamicin and vancomycin from polymethylmethacrylate (PMMA) spacers before and after implantation for the treatment of total hip replacement infections. METHODS: Twenty industrially produced spacers containing gentamicin (1.9%) were utilized. Vancomycin (2.5%) mixed with PMMA cement was used to fill holes drilled in the cement of 14 of the 20 spacers immediately before implantation. The spacers were removed from 20 patients 3-6 months after implantation and then immersed in phosphate buffer at 37 degrees C for 10 days. Antibiotic concentrations were determined by fluorescence polarization immunoassay. RESULTS: Gentamicin and vancomycin were still present in all the spacers removed from the patients. The release of gentamicin alone and in combination with vancomycin was in the range 0.05%-0.4% of the initial amount present, whereas the release of vancomycin was in the range 0.8%-3.3%. The release kinetics showed a similar pattern for both drugs. After a high initial release of drug, a reduced, but constant, elution was observed over the next few days. CONCLUSIONS: The delivery of gentamicin and vancomycin from PMMA cement was high initially, with sustained release over several months. Incorporation of vancomycin into the surface of the spacers permitted spacers to be prepared with multiple antibiotics present and without adversely affecting the release kinetics of the agents. The gentamicin-vancomycin combination shows potential for the treatment of infection following total hip replacement in specific patients.     

The combination of ultrasound with antibiotics released from bone cement decreases the viability of planktonic and biofilm bacteria: an in vitro study with clinical strains

OBJECTIVES: Antibiotic-loaded bone cements are used for the permanent fixation of joint prostheses. Antibiotic-loaded cements significantly decrease the incidence of infection. The objective of this study was to investigate whether the viability of bacteria derived from patients with a prosthesis-related infection could be further decreased when antibiotic release from bone cements was combined with application of pulsed ultrasound. METHODS: Escherichia coli ATCC 10798, Staphylococcus aureus 7323, coagulase-negative staphylococci (CoNS 7368 and CoNS 7391) and Pseudomonas aeruginosa 5148 were grown planktonically in suspension and as a biofilm on three different bone cements: Palacos R without gentamicin as control, gentamicin-loaded Palacos R-G and gentamicin/clindamycin-loaded Copal. The viability of planktonic and biofilm bacteria was measured in the absence and presence of pulsed ultrasound for 40 h. RESULTS: Ultrasound itself did not affect bacterial viability. However, application of pulsed ultrasound in combination with antibiotic release by antibiotic-loaded bone cements yielded a reduction of both planktonic and biofilm bacterial viability compared with antibiotic release without application of ultrasound. CONCLUSIONS: This study shows that antibiotic release in combination with ultrasound increases the antimicrobial efficacy further than antibiotic release alone against a variety of clinical isolates. Application of ultrasound in combination with antibiotic release in clinical practice could therefore lead to better prevention or treatment of prosthesis-related infections.     

Optimized elution of daptomycin from polymethylmethacrylate beads

We demonstrate that xylitol can be added to polymethylmethacrylate (PMMA) bone cement to enhance the elution of daptomycin in terms of both the peak and sustained release of antibiotic. We also demonstrate that a PMMA-xylitol formulation optimized for daptomycin can be used to enhance the elution of both vancomycin and gentamicin.     

Elution kinetics,antimicrobial activity,and mechanical properties of 11 different antibiotic loaded acrylic bone cement

Antibiotic-loaded acrylic bone cements (ALABC) spacers are routinely used in the treatment of prosthetic joint infections. The objectives of our study were to evaluate different ALABC for elution kinetics, thermal stability, and mechanical properties. A 10 or 20% mixture (w/w) beads of medium viscosity bone cement (DePuy, Inc) and vancomycin (VAN), gentamycin (GM), daptomycin (DAP), moxifloxacin (MOX), rifampicin (RIF), cefotaxime (CTX), cefepime (FEP), amoxicillin clavulanate (AmC), ampicillin (AMP), meropenem (MER), and ertapenem (ERT) were formed and placed into wells filled with phosphate-buffered saline. Antibiotic concentrations were determined using high-performance liquid chromatography. Antimicrobial activity was tested against Micrococcus luteus ATCC 9341 or Escherichia coli ATCC 25922. AmC, AMP, and FEP concentration rapidly decreased after day 2, being almost undetectable at day 4. Sustained and high elution rates were observed with VAN, GM, MOX, and RIF for the 30-day duration of the experiment. DAP, MER, ERT, and CTX elution rates constantly decreased from day 4. All antibiotics tested retained antimicrobial activity proving thermal stability. Mechanical properties of ALABC were maintained except when RIF was used.     

Contrasting effects of physical wear on elution of two antibiotics from orthopedic cement

The use of antibiotics as a supplement to bone cement for the purposes of providing a local release of antibiotics is common practice in arthroplasty surgery and the kinetics of elution of the antibiotics in such systems have been investigated previously. However, in these previous studies no account was taken of the potential effects that wear may have on the elution kinetics of the antibiotic. Here, we have modified an existing wear testing rig to allow the simultaneous study of the elution kinetics of bone cement samples containing antibiotics being subjected to immersion only and immersion and conjoint wear. The results show contrasting effects with two commonly used antibiotics. Bone cement containing daptomycin showed no substantial change in antibiotic elution due to wear, while cement containing gentamicin (the most commonly used antibiotic in this application) in contrast demonstrated a substantial reduction in the rate of antibiotic elution when wear was applied. Scanning electron microscopy revealed a possible explanation for these diverse results, due to wear-induced "sealing" of the surface in conjunction with the crystal morphology of the antibiotic.     

不同种类抗生素影响重症肌无力小鼠神经肌肉接头处的传递功能

背景临床工作发现多种抗生素可影响甚至加重重症肌无力已存在的神经肌肉接头处传递功能的障碍,使患者的肌无力症状恶化.目前,国内外在重症肌无力动物模型上进行抗生素对神经肌肉接头处传递功能影响的报道较少.随着新型抗生素的出现,有必要进一步探讨各类抗生素对神经肌肉接头处传递功能的影响.目的探讨头孢菌素类、喹诺酮类和氨基糖甙类抗生素对重症肌无力神经肌肉接头处传递功能的影响,为临床安全、合理选用抗生素治疗重症肌无力提供实验依据.设计以实验动物为研究对象,随机对照试验.单位一所大学医院的感染科、神经内科和药剂科.材料实验于2002-03/2003-01在华中科技大学同济医学院神经科学研究所完成.健康、雌性C57BL/6小鼠150只,随机分为正常组10只;重症肌无力组10只;生理盐水组10只;抗生素治疗组120只.抗生素治疗组分为庆大霉素组、依米替星组、环丙沙星组、氟罗沙星组、头孢呋新组和头孢他啶组,每组20只.干预以丁氏双鳍电鳐的电器官的乙酰胆碱受体免疫3次建成EA重症肌无力模型.生理盐水组、各抗生素治疗组于末次免疫后第7天开始按10 mg/kg体质量分别注射生理盐水和抗生素,连续注射14 d;重症肌无力组和正常组不做任何处理.分别于末次免疫后第7天和抗生素治疗后第14天进行症状评分、低频重复电刺激检查和血清中乙酰胆碱受体抗体水平的检测.主要观察指标①肌无力症状评分.②低频重复电刺激的衰减率.③血清乙酰胆碱受体抗体的水平.结果注射抗生素后第14天庆大霉素组、依米替星组、环丙沙星组和氟罗沙星组小鼠的平均症状评分明显高于重症肌无力组,头孢呋新组和头孢他啶组小鼠的平均症状评分与重症肌无力组无明显差别;低频重复电刺激检测衰减幅度庆大霉素组(21.22±4.63)%、依米替星组(19.08±4.25)%、环丙沙星组(22.25±4.95)%和氟罗沙星组(21.71±4.99)%明显高于重症肌无力组(15.75±2.22)%,头孢呋新组(15.25±2.87)%和头孢他啶组(15.25±3.30)%与重症肌无力组无明显差别;乙酰胆碱受体抗体水平庆大霉素组、依米替星组、环丙沙星组和氟罗沙星组明显高于重症肌无力组,头孢呋新组和头孢他啶组与重症肌无力组无明显差别.结论氨基糖甙类和喹诺酮类抗生素可以加重重症肌无力小鼠业已存在的神经肌肉接头处传递功能的障碍,而头孢菌素类抗生素没有明显的影响.