Objective To prepare cationic Vancomycin hydrochloride multivesicular liposome (MVL) and to inspect its quality. Methods Cationic Vancomycin hydrochloride MVLs were prepared by double emulsion method, and the storing solution of Vancomycin was prepared. The analysis method of Vancomycin in vitro was established; the specificity, precision, and resorption rate were estimated. Reverse phase high performance liquid chromatography (RP-HPLC) was used to determine the concentration of Vancomycin, encapsulation efficiency, and release characteristics in vitro. The formulation and pharmaceutical process were optimized by single factor experiments and orthogonal experimental design with the factor of encapsulation efficiency as the criteria. The liposome morphology was observed by optical microscopy and transmission electron microscopy. The particle size and Zeta potential were determined by Malvern instrument. The stability was analyzed by dynamic analysis. Results An RP-HPLC method was established for the assay of Vancomycin. The analysis method was precise, simple, and reliable for the quality control of Vancomycin. Vancomycin hydrochloride MVLs were round and well-distributed. The average particle size and the encapsulation efficiency were 3.3 μm and 24.9%, respectively. Zeta potential was 24.53 mV, and 90.5% of Vancomycin hydrochloride was released after 264 hours in normal saline under 37℃. Cationic Vancomycin MVLs were stored for 1 month at 4 ℃, which mantained good stability. Conclusion Cationic Vancomycin hydrochloride MVLs have good appearance, high encapsulation efficiency, good stability, and significant sustained release properties.
【Abstract】 Objective To investigate the anti-infection and bone repair effects of cationic l i posome-encapsulatedvancomycin combined with the nano-hydroxyapatite/chitosan/konjac glucomannan (n-HA/CS/KGM) composite scaffold invivo. Methods Fifty-one 6-month-old New Zealand white rabbits, weighing 1.5-3.0 kg, were selected to prepare chronicinfectious tibia bone defect model by using Staphylococcus aureus. After 4 weeks, 48 survival rabbits were randomly divided into 4 groups (n=12). After debridement, defect was treated with nothing in group A, with n-HA/CS/KGM composite scaffold in group B, with vancomycin and n-HA/CS/KGM composite scaffold in group C, and with cationic l i posome-encapsulated vancomycin and n-HA/CS/KGM composite scaffold in group D. After 8 weeks of treatment, general observation, X-ray, HE staining, the bacterial culture, and the measurement of the longest diameter of bone defect were done. Results At 4 weeks after modeling, 48 rabbits were diagnosed as having osteomyelitis, including periosteal new bone formation, destruction of bone, and soft tissue swell ing. The Norden score was 3.83 ± 0.52. At 8 weeks after treatment, sinus healed in groups C and D, but sinus was observed in groups A and B; the gross bone pathologieal scores of group D were significantly better than those of groups A and B (P lt; 0.05). Bone defects were repaired completely in group D, the results of the longest diameter of bone defects in group D was significantly better than those in the other 3 groups (P lt; 0.05). New bone formation was observed in groups C and D, but periosteal reactionand marrow low-density shadow were observed in groups A and B; Norden score in group D was significantly better than those in groups A, B, and C (P lt; 0.05). HE staining showed that there were a large number of trabecular bone formation and fibrosis, with no obvious signs of infection in groups C and D, but neutrophil accumulation was observed in groups A and B; Smeltzer scores in groups C and D were significantly better than those in groups A and B (P lt; 0.05). Bacteriological results showed higher negative rate in groups C and D than in groups A and B (P lt; 0.05). Conclusion Cationic l iposome-encapsulated vancomycin and n-HA/CS/KGM composite scaffold can be a good treatment for infectious bone defects in rabbits, providing a new strategy for the therapy of bone defects in chronic infection.
Objective To evaluate the characterization, biocompatibil ity in vitro and in vivo, and antimicrobial activity of an injectable vancomycin-loaded borate glass/chitosan composite (VBC) so as to lay the foundation for its further cl inical application. Methods The sol id phase of VBC was constituted by borate glass and vancomycin, liquid phase was a mixture of chitosan, citric acid, and glucose with the proportion of 1 ∶ 10 ∶ 20. Solid phase and liquid phase was mixed withthe ratio of 2 ∶ 1. Vancomycin-loaded calcium sulfate (VCS) was produced by the same method using calcium sulfate instead of borate glass and sal ine instead of chitosan, as control. High performance liquid chromatography was applied to detect the release rate of antibiotics from VBC and VCS, and minimum inhibitory concentration (MIC) was tested by using an antibiotic tube dilution method. The structure of the VBC and VCS specimens before and 2, 4, 8, 16, and 40 days after immersion in D-Hank’s was examined by scanning electron microscopy, and the phase composition of VBC was analysed by X-ray diffraction after soaked for 40 days. Thirty-three healthy adult New Zealand white rabbits (weighing, 2.25-3.10 kg; male or female) were used to establ ish the osteomyel itis models according to Norden method. After 4 weeks, the models of osteomyel itis were successfully established in 28 rabbits, and they were randomly divided into 4 groups (groups A, B, C, and D). In group A (n=8), simple debridement was performed; in groups B and C (n=8), defect was treated by injecting VCS or VBC after debridement; and in group D (n=4), no treatment was given. The effectiveness of treatment was assessed using radiological and histological techniques after 2 months. Results The releases of vancomycin from VBC lasted for 30 days; the release rate of vancomycin reached 75% at the first 8 days, then could reached more than 90%. The releases of vancomycin from VCS lasted only for 16 days. The MIC of VBC and VCS were both 2 μg/mL. The VCS had a smooth glass crystal surface before immersion, however, it was almost degradated after 4 days. The fairly smooth surface of the VBC pellet became more porous and rougher with time, X-ray diffraction analysis of VBC soaked for 40 days indicated that the borate glass had gradually converted to hydroxyapatite. After 2 months, the best result of treatment was observed in group C, osteomyelitis symptoms disappeared. The X-ray scores of groups A, B, C, and D were 3.50 ± 0.63, 2.29 ± 0.39, 2.00 ± 0.41, and 4.25 ± 0.64, respectively; Smeltzer scores were 6.00 ± 0.89, 4.00 ± 0.82, 3.57 ± 0.98, and 7.25 ± 0.50, respectively. The scores were significantly higher in group D than in groups A, B, and C (P lt; 0.05), and in group A than in groups B and C (P lt; 0.05). The scores were higher in group B than in group C, but no significant difference was found (P gt; 0.05). Conclusion The VBC is effective in treating chronic osteomyelitis of rabbit by providing a sustained release of vancomycin, in addition to stimulating bone regeneration, so it may be a promising biomaterial for treating chronic osteomyelitis.
Objective Bioactive borate glass (BG) has good biocompatibil ity and biodegradation. To investigate the feasibilty of bioactive borate glass as a carrier of the antibiotic controlled-releasing by implanting vancomycin-loaded BG (VBG)into the focus of tibia chronic osteomyel itis after debridement. Methods VBG and vancomycin-loaded calcium sulfate (VCS) were prepared with a vancomycin content of 80 mg/g. Sixty-five New Zealand white rabbits, weighing 2.12-3.91 kg (mean, 2.65 kg), were used. The tibia chronic osteomyel itis rabbit models were establ ished by injecting methicill in-resistant Staphylococcus aureus (MRSA, 0.1 mL, 1 × 109 cfu/mL) into the right tibia of 65 rabbits. After 3 weeks of injection, 54 rabbits of successful models were randomly divided into groups A (n=11), B (n=11), C (n=16), and D (n=16). Simple debridement was performed in group A; BG, VCS, and VBG were implanted into the infection sites of groups B, C, and D respectively after thorough debridement. A sample of the debrided tissues was harvested for bacterial examination. The vancomycin serum levels were determined in groups C and D at 1, 2, 4, 10, 24, and 48 hours after operation. The boron serum levels were determined in groups B and D at 10, 24, 48, 72, and 120 hours after operation. After 8 weeks, the effectiveness was assessed radiographically, bacteriologically, and histopathol ogically. Results Ten rabbits died after operation. No vancomycin was detected in group C; the vancomycin level increased gradually, reached the highest level at 4 hours after operation, and then decreased rapidly in group D. No boron was detected in group B; the boron reached the highest serum level at 10 hours after operation, and then decreased gradually in group D. At 8 weeks, calcium sulfate degraded in group C; BG degraded partially in group D; and no obvious degradation was observedin group B. The repair effect was better in group D than in group C. There was no significant difference in radiograph scoring between groups A, B, C and D (P gt; 0.05) before operation, but there was significant difference between group D and groups A, B, C (P lt; 0.05) at 8 weeks after operation. The bacterial culture showed that all the MRSA results were positive in 4 groups. At 8 weeks, the negative rates of MRSA examination were 36.36%, 18.18%, 73.33%, and 81.25% respectively in groups A, B, C, and D, showing significant differences between group D and groups A, B (P lt; 0.05). The histopathological observation showed that a large number of new bones formed and no foreign body reaction occurred in group D. The histopathologic scores of groups A, B, C, and D were 6.45 ± 3.62, 7.55 ± 3.36, 4.27 ± 2.91, and 3.81 ± 3.04 respectively, showing significant differences between group D and groups A, B, and between group C and group B (P lt; 0.05). Conclusion VBG can improve the repair of bone defect in the treatment of chronic osteomyel itis.
Objective To study the effect of vancomycin-loaded polymethylmethacrylate (VCMPMMA) in the treatment of an experimental hemiprosthetic hip infectionof rabbits. Methods The infected hemiprosthetic hip joints of the rabbits underwent debridement and one-stage revision arthroplasty. Requested by the “fixed” method, 24 rabbits were equally divided into 2 groups: the control group and theexperimental group. The prostheses were fixed with PMMA in the control group, but with VCM-PMMA in the experimental group. X-ray films were taken immediately after operation, and then 4, 8, and 12 weeks after operation. The C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured before operation, then measured 1, 3, and 7 days after operation, and then 2, 4, 8, and 12 weeks after operation, i.e., they were measured at the above 8 time points. All the rabbits were sacrificed 12 weeks later. The cure rate of the infection was determined by the blood culture for the corresponding bacteria and the Rhodamine-labeled anti-Staphylococcus epidermidisimmune serum staining. Results The X-ray films revealed that6 hemiprosthetic hip joints were dislocated in the control group, but 3 in the experimental group; 58.3% and 16.7% of the hemiprosthetic hip joints were reinfected in the control group and the experimental group, respectively. At 8 weeks in the control group, the serum CRP level decreased to a greater extent than that measured at the time of debridement, but in the experimental group just at 2 weeks （Plt;0.01）. ESR remained elevated in the control group, but at 4 weeks ESR were significantly lowered compared with that measured at the time of debridement（Plt;0.01）. The test results for the pathogenic organisms revealed that the re-infection incidences were respectively 58.3% (7/12) and 16.7% (2/12) in the control group and the experimental group, with the successful revision rates of 41.7% and 83.3% respectively in the above 2 groups. The light microscopy revealed that therewas a heavy infiltration by the inflammatory cells in the reinfected tissues, but there was a proliferation of the fibrocytes in the tissues of the cured patients. Conclusion Onestage revision arthroplasty can significantly promote the control of the hemiprosthetic hip joint infection in rabbits by the use of VCM-PMMA.
Objective To compare the effectiveness and safety of linezolid with vancomycin for the treatment of people with Gram-positive bacteraemia. Methods We electronically searched The Cochrane Library (Issue 1, 2009), MEDLINE, EMbase, Current Controlled Trials, The National Research Register, CBM disc and CNKI. We also handsearched some relevant journals. The search time was up to March 10, 2009. Randomized controlled trials of linezolid versus vancomycin for treatment of Gram-positive bacteraemia were included. Meta-analyses were performed for the results of homogeneous studies using the Cochrane Collaboration’s RevMan 5.0 software. Results A total of 8 randomized controlled trials involving 670 patients with Gram-positive bacteraemia were included. The results indicated that there was no significant difference between linezolid and vancomycin groups in treatment of Gram-positive bacteraemia [RR= 1.07, 95%CI (0.98,1.17), P= 0.15], MRSA bacteraemia [RR=1.22, 95%CI (0.97,1.53), P= 0.10] or catheter-related bacteraemia [RR= 1.01, 95%CI (0.86,1.19), P= 0.90]. There was no difference between groups in the total adverse effect (P=0.64). The rate of renal dysfunction was higher in vancomycin group (P=0.0003) and the rate of thrombopenia was higher in linezolid group (P=0.01). Conclusion Linezolid is associated with the outcomes that are not inferior to those of vancomycin in the patients with Gram-positive bacteraemia. More high-quality, large-scale randomized controlled trials exclusive for the bacteraemia are required.
ObjectiveTo systematically review the therapeutic effects and safety of teicoplanin versus vancomycin for severe gram-positive bacterial infection. MethodsWe electronically searched CBM, CNKI, VIP, WanFang Data, PubMed, EMbase, The Cochrane Library (Issue 3, 2013) and Springer for the internationally-nationally published randomized controlled trials (RCTs) on teicoplanin versus vancomycin for severe gram-positive bacterial infections from inception to October 2013. Two reviewers screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then meta-analysis was performed using RevMan 5.2 software. ResultsTwenty RCTs were finally included, involving 1 555 patients with severe gram-positive bacterial infection. The results of meta-analysis showed that there was no significant difference between teicoplanin and vancomycin with regard to all-cause mortality (OR=1.67, 95%CI 0.86 to 3.23, P=0.13), clinical cure rates (OR=1.24, 95%CI 0.95 to 1.60, P=0.11), effective rates (OR=1.03, 95%CI 0.75 to 1.41, P=0.87), and bacterial clearance rates (OR=0.96, 95%CI 0.66 to 1.39, P=0.83). However, the incidence of adverse reaction was lower in the teicoplanin group than in the vancomycin with a significant difference (OR=0.50, 95%CI 0.34 to 0.72, P=0.000 2). ConclusionThe results of meta-analysis shows that, teicoplanin is similar to vancomycin in therapeutic effects on treating severe gram-positive bacterial infection but it is better in safety. However, because of limited quantity and quality of the included studies, the above conclusion needs to be further verified by conducting more high-quality studies.
ObjectiveTo systematically evaluate the efficacy and safety of teicoplanin versus vancomycin for lower respiratory tract infection with gram-positive bacteria in Chinese population. MethodsThe PubMed, EMbase, The Cochrane Library (Issue 3, 2016), CNKI, and WanFang Data databases were searched from their inception to March 20, 2016, to collect randomized controlled trials about teicoplanin versus vancomycin for lower respiratory tract infection with gram-positive bacteria in Chinese population. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. ResultsA total of 12 RCTs involving 921 patients were included. The results of meta-analysis suggested that there were no significant associations between the teicoplanin group and the vancomycin group in total effective rate (RR=0.99, 95%CI 0.93 to 1.05, P=0.69), clinical cure rate (RR=1.05, 95%CI 0.92 to 1.19, P=0.49), and bacteria clearance rate (RR=1.00, 95%CI 0.93 to 1.05, P=0.69). However, the teicoplanin group had lower incidences of the total adverse event (RR=0.65, 95%CI 0.47 to 0.90, P=0.008) and nephrotoxicity (RR=0.33, 95%CI 0.16 to 0.66, P=0.002), and shorter course of treatment (MD=-1.78, 95%CI -3.27 to -0.29, P=0.02) than that in the vancomycin group. ConclusionCurrent evidence indicates that teicoplanin is similar to vancomycin in therapeutic effects on treating lower respiratory tract infection with gram-positive bacteria in Chinese population, but teicoplanin is better in safety and has a shorter course of treatment than vancomycin. Due to limited quantity and quality of the included studies, more high-quality RCTs are needed to confirm the above conclusions.
Objective To explore the clinical efficiency of vancomycin-loaded calcium phosphate cement (CPC) in the treatment of chronic osteomyelitis (CO). Methods From December 1st 2014 to December 1st 2015, 98 patients with CO were randomly divided into the research group and the control group, with 49 in each group. The patients in the research group were primarily implanted with vancomycin-loaded CPC after debridement, while the ones in the control group were placed with irrigation and drainage device to take continous irrigation with antibiotics after debridement. The treatment effect and the recurrence rate in the two groups were observed. Results The patients in the two groups were followed up for 12 months. In the research group, 30 patients were cured, 16 were improved, and 3 were not improved with the total effective rate of 93.9%; no systemic adverse reactions and recurrence took place after the operation; X-ray results showed well CPC tamponade and partially degenerated osteogenesis. In the control group, 16 patients were cured, 20 were improved and 13 were not improved, with the total effective rate of 73.5%; 11 had recurrent inflammation in 2–6 months after operation and were reoperated again. Conclusion The primary implantation of vancomycin-loaded CPC in CO lesions can fill the dead space, resist infection persistently, induce osteogenesis in bone defect area, and reduce the recurrence of CO, which is an effective method for the treatment of CO.