Diffusion of ertapenem into bone and synovial tissues

OBJECTIVES: The degree of penetration of an antibiotic into the infected site is an important criterion for therapeutic success. Ertapenem is a new carbapenem, exhibiting activity against most Gram-positive and Gram-negative aerobic and anaerobic bacteria commonly recovered from community-acquired infections. However, no studies concerning its diffusion into bone and synovial tissue are available. Our objective was to quantify ertapenem bone and synovial tissue penetration and to compare our data with the MIC(90)s for causative pathogens. PATIENTS AND METHODS: In an open-label study, 18 patients who were undergoing elective total hip replacement received a single, parenteral, 1 g dose of ertapenem. One serum, one cortical and cancellous bone and one synovial tissue sample was collected per patient a median [interquartile range (IQR)] of 1.6 (1.5-1.7), 12.4 (11.9-13.1) or 23.8 h (22.6-25.2) later and analysed by HPLC. RESULTS: The median (IQR) serum concentrations of ertapenem were 70.1 (56.1-75.9), 10.0 (9.1-11.2) and 2.6 mg/L (2.3-3.0), respectively, at the different time points. The median (IQR) cancellous bone tissue concentrations were 13.2 (10.2-14.8), 1.9 (1.7-2.1) and 0.6 microg/g (0.4-0.6) at the different time points, corresponding to a median (IQR) tissue/serum penetration ratio of 0.19 (0.18-0.23). The median (IQR) cortical bone tissue concentrations were 8.0 (6.5-9.5), 1.3 (1.2-1.3) and 0.3 microg/g (0.3-0.4) at the different time points, corresponding to a median (IQR) tissue/serum penetration ratio of 0.13 (0.12-0.14). The median (IQR) synovial tissue concentrations were 26.2 microg/g (22.7-28.4), 4.0 mg/L (3.7-4.4) and 1.0 mg/L (0.9-1.2) at the different time points, corresponding to a median (IQR) tissue/serum penetration ratio of 0.41 (0.39-0.42). CONCLUSIONS: The concentrations after an ertapenem 1 g dose achieved in cancellous and cortical bone tissue and in synovial tissue were greater than the MIC(90)s for most aerobic organisms for 24 h, and for 12 to 24 h for anaerobic bacteria in healthy volunteers undergoing total hip replacement.     

Aztreonam penetration into synovial fluid and bone.

Eighteen patients with uncomplicated degenerative joint disease requiring joint replacement (hip or knee) were given a single 2-g intravenous dose of aztreonam over a 5-min period preoperatively. The mean concentration in synovial fluid of 83.0 +/- 9.2 micrograms/ml averaged 0.99 times the concomitant levels in serum. The mean concentration in cancellous bone of 16.0 +/- 4.3 micrograms/g averaged 0.20 times the concomitant levels in serum.     

Penetration of piperacillin-tazobactam into cancellous and cortical bone tissues.

The penetration characteristics of piperacillin-tazobactam into cortical and cancellous bone tissues were investigated in 10 patients undergoing total hip replacement. The concentration ratios of piperacillin/tazobactam were 9.4 +/- 1.8 in cancellous bone tissue and 8.0 +/- 2.2 in cortical bone tissue, which were close to the 8:1 ratio of drugs administered. The mean ratios of drug concentrations in bone and plasma for cancellous and cortical tissue were 23 and 18%, respectively, for piperacillin and 26 and 22%, respectively, for tazobactam. The concentrations of tazobactam achieved are sufficient to exert anti-beta-lactamase activity and supportive of clinical trials involving bone and joint infections, including those caused by beta-lactamase-producing pathogens.     

Linezolid penetration into bone and joint tissues infected with methicillin-resistant staphylococci

Penetration of linezolid into bone and joint tissues was studied by high-performance liquid chromatography in 13 patients suffering from implant-associated infections with methicillin-resistant staphylococci. Mean concentrations of linezolid in infected tissues were greater than 10 mg/liter in a sampling time range of 35 to 124 min after administration of the preoperative dose, except in bone specimens, where they reached 3.9 +/- 2.0 mg/liter.     

Osteoarthritis. Effects on synovial joint tissues

The purposes of this article are 1) to provide an updated summary of some aspects of research into osteoarthritis and 2) to stimulate physical therapy inquiry on its causes, effects, and treatments. The current literature concerning the pathological changes associated with osteoarthritis is reviewed in the context of specific joint tissues (ie, articular cartilage, bone, synovial membrane, capsule and capsular ligaments, muscle, and nerve). Correlations are drawn between the pathological effects of osteoarthritis on these tissues and commonly observed clinical changes. Gaps in the current research literature are discussed, and areas needing further research are highlighted.     

The penetration of trimethoprim and sulphamethoxazole into synovial fluid

A group of six patients with non-infected synovial effusions requiring diagnostic or therapeutic aspiration, were given a short oral course of 'Septrin' (two tablets bd for two doses, each tablet containing 80 mg of trimethoprim plus 400 mg of sulphamethoxazole). Serum and synovial fluid (SF) were sampled frequently following antibiotic administration. It was found that concentrations of trimethoprim in SF approached serum levels after a short lag time (about 3 h) and thereafter approximated to the serum levels, whereas sulphamethoxazole did not as readily penetrate into SF. With the regimens used MIC levels for trimethoprim were achieved in SF, which suggests that this drug could be usefully prescribed in normal doses for the treatment of septic arthritis due to bacterial infection.     

骨性关节炎患者退变软骨及滑膜组织中细胞因子的表达

背景：骨性关节炎的炎症反应是Fh软骨细胞、滑膜组织分泌的细胞因子所介导的。关节软骨和滑膜组织内含有多种细胞因子,在关节软骨的损伤修复中起着重要的调节作用。目的：分析软骨细胞、滑膜组织分泌的细胞因子与骨性关节炎发病的关系及影响。方法：由第一作者应用计算机检索万方数据库（WWW．wanfangdata．com．cn）,PubMed数据库（www．ncbi．nIm．nih．guv／pubmed）检索时间：2005至2010年。检索词为“骨性关节炎,退变,软骨组织,细胞因子”。计算机初检得到146篇文献,阅读标题和摘要进行初筛,排除因研究目的与此文无关的86篇,内容重复性的研究40篇,保留21篇骨性关节炎患者退变软骨及滑膜组织中各种细胞因子作用及影响的相关文献作进一步分析。结果与结论：细胞因子主要是指活化的免疫细胞和某些基质细胞分泌的一类非特异调节免疫应答和介导炎症反应的小分子蛋白质,包括由淋巴细胞产生的淋巴因子,单核巨噬细胞产生的单核因子及其他细胞因子等。关节滑膜细胞分泌的细胞因子可部分解释骨性关节炎的病理过程,在炎症关节中起着重要的作用。虽然越来越多的学者重视到滑膜细胞、软骨细胞分泌细胞因子的作用,但主要是研究外源性细胞因子对软骨细胞或滑膜细胞的影响,而其内源性细胞因子在骨性关节炎发病中的作用却未广泛开展研究。     

Nitrogen Diffusion into Closed Anesthesia Systems

Objective. In order to reduce losses of gases through plastic components and to reduce nitrogen accummulation during closed system anaesthesia we investigated either 10 sets of anaesthetic tubing made of silicon as used in standard clinical practice and 10 sets made of latex, which are not used anymore due to concerns about latex allergies. The results were compared to each one set made of conventional industrial rubber. Methods. Anaesthetic tubings were connected to ventilators with low fresh gas losses, suitable for closed system anaesthesia. For nitrogen measurements, a mass spectrometer was used.The fresh gas flow was set to exceed losses by leakages and the amount of gases, extracted from the system by the mass spectrometer. Results. Highest accumulation of nitrogen was found using tubings made of silicone. Conclusion. If closed anaesthetic systems in the future will be used in intensive care therapy or in case of long lasting procedures in which closed system anaesthesia is proceeded, materials other than silicone should be investigated to avoid regular purging of system and consecutive losses of gas mixtures.     

Diffusion of tosufloxacin into prostatic tissue.

The diffusion of tosufloxacin (TFLX) into the prostatic tissue was studied in 25 patients with benign prostatic hypertrophy. TFLX concentrations in the serum and prostatic tissue were measured at scheduled intervals after oral administration of 450 mg of TFLX on the day before surgery, followed by administration of 150 mg of TFLX immediately before surgery. The mean TFLX levels in prostatic tissue (and tissue/serum levels) at 2, 4 and 6 h were 0.35 +/- 0.16 microgram/g (0.93 +/- 0.36) in 7 patients, 0.58 +/- 0.92 microgram/g (1.10 +/- 0.45) in 10 patients and 0.22 +/- 0.09 microgram/g (0.95 +/- 0.45) in 8 patients. The TFLX levels in prostatic tissue exceeded the minimum inhibitory concentration for several pathogenic bacteria detected in the infected prostatic fluid. Therefore, TFLX shows promise as a useful drug in the treatment of bacterial prostatitis and infections developing after prostatic surgery.     

Linezolid penetration into osteo-articular tissues

Penetration of linezolid into osteo-articular tissue and fluid was studied in 10 patients undergoing primary total knee replacement. Linezolid 600 mg 12 hourly was given orally over the 48 h before operation and intravenously 1 h before induction of anaesthesia. Mean concentrations of linezolid at 90 min after the final dose, in serum, synovial fluid, synovium, muscle and cancellous bone, assayed by HPLC, were at least twice the MIC(90) for staphylococci and streptococci. The concentrations obtained indicate good penetration of this antibiotic and support its use in the management of multidrug-resistant Gram-positive bone, joint and deep-seated soft-tissue infections.     

In vivo measurement of levofloxacin penetration into lung tissue after cardiac surgery

Nosocomial pneumonia is a severe complication after cardiac surgery (CS). Levofloxacin, a fluoroquinolone, qualifies for the therapy of postoperative pneumonia. However, penetration properties of levofloxacin into the lung tissue could be substantially affected by CS: atelectasis, low cardiac output after CS, high volume loads, and inflammatory capillary leak potentially influence drug distribution. The aim of our study was to gain information on interstitial antibiotic concentrations in lung tissue in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. Therefore, six patients undergoing elective CS participated in this prospective study. A dose of 500 mg of levofloxacin was administered intravenously in addition to standard antibiotic prophylaxis immediately after the end of surgery. Time versus concentration profiles of levofloxacin in the interstitial lung tissue and plasma were determined. A microdialysis technique was used for lung interstitial concentration measurements. The microdialysis procedure was well tolerated in all patients and no adverse events were observed. The median area under the concentration curve (AUC) of levofloxacin in interstitial lung fluid was 18.6 microg.h/ml (range, 10.1 to 33.6). The median AUC for tissue (AUC(tissue)) of unbound levofloxacin/AUC(total) in plasma was 0.6 (range, 0.4 to 0.9). The median unbound AUC(tissue)/MIC was 2.4 (range, 1.3 to 4.2) for Pseudomonas aeruginosa. Our study demonstrated the feasibility and safety of microdialysis in human lung tissue in vivo after CS. The unbound AUC/MIC ratio revealed that levofloxacin used in the described manner was borderline sufficient for the treatment of nosocomial pneumonia caused by Klebsiella pneumoniae and insufficient for the treatment of pneumonia caused by Pseudomonas aeruginosa, because the breakpoint of 30 to 40 for AUC/MIC could not be reached by the conventionally used dosage schema in our post-CS setting. Penetration was lower than in previous reports.     

Electrotransfer of therapeutic molecules into tissues

Electroporation is a physical method for the delivery of various molecules into cells by application of controlled external electrical fields that transiently increase permeability of the cell membrane. This technique is now widely used as an alternative to viral gene delivery for transfection of therapeutic genes into different tissues. Gene electrotransfer holds great potential for clinical application due to the ease of preparation of large quantities of endotoxin-free plasmid DNA, the control and reproducibility of this method, and the development of electric pulse generators approved for clinical use. Electroporation has been utilized mainly for DNA vaccination against infectious diseases and cancer. It has also been used for the delivery of other therapeutic genes, mainly cytokines, used in the treatment of various diseases, including cancer, arthritis, multiple sclerosis and inflammation, following organ transplantation. Electroporation as a delivery system for chemotherapeutic drugs, termed antitumor electrochemotherapy, is already at the clinical stage and is being used routinely in several oncology centers in Europe. In addition, the first clinical trials for electrogene therapy of cancer are ongoing. Therefore, it can be presumed that electrotransfer of therapeutic genes into tissues will soon form a validated alternative to viral delivery systems in a clinical setting.     

Diffusion of pain management research into nursing practice

The promotion of evidence based practice is a challenge within nursing. Pain management is a prime example of this practice research gap. There is solid evidence for 20 years to promote positive change in our methods of pain management, yet outdated approaches are still amazingly evident. Even among oncology nurses, who place a high value on promoting patient comfort, there is a lack of evidence-based pain management. Rogers' Diffusion of Innovation Theory provides an interesting framework for examining the issues and possible solutions to this complex problem. Rogers' theory examines how changes diffuse through a social system over time and also exposes some of the barriers and facilitators to this process. The theory looks at adopters, the nature of the innovation, the social system, and communication patterns. Identifying the barriers of the past will help nursing to overcome these same barriers and increase the adoption of evidence-based pain management approaches in the future.