Delivery Of Vancomycin Research Articles

Novel Alginate-Chitosan Composite Microspheres for Implant Delivery of Vancomycin and In Vivo Evaluation.

In this study, vancomycin loaded alginate-chitosan composite microspheres were developed by emulsion cross-linking method. The in vitro and vivo characterizations were done to evaluate the feasibility of application. Our experimental results showed that the emulsification cross-linking technique appeared to be a feasible method for the preparation of alginate-chitosan composite microspheres. The microspheres were spherical in shape and the mean particle size and drug loading were 25.3 ± 5.4 μm and 18.5 ± 2.3% respectively. A sustained vancomycin release was realized i.e. the amount of cumulative release increased in a time frame of 24 h to reach an amount i.e. ~68%. The model that fit best for vancomycin released from the microspheres was the Higuchi kinetic model with a correlation coefficient r = 0.9996. In vivo results showed that the application of microspheres not only reduced the toxicity, but also maintained effective drug concentration. In addition, no severe signs of epithelial necrosis and sloughing of epithelial cells were detected in histological studies.

Nanoparticles as tool for enhanced ophthalmic delivery of vancomycin: a multidistrict-based microbiological study, solid lipid nanoparticles formulation and evaluation

Context: A microbiological multidistrict-based survey from different Egyptian governorates was conducted to determine the most prevalent causative agents of ocular infections in the Egyptian population. Antibiotic sensitivity testing was then performed to identify the most potent antimicrobial agent. Vancomycin (VCM) proved the highest activity against gram-positive Staphylococcus bacteria, which are the most commonly isolated causative agents of ocular infection. However, topically applied VCM suffers from poor ocular bioavailability because of its high molecular weight and hydrophilicity. Objective: The aim of the present study was to develop VCM-loaded solid lipid nanoparticles (SLNs) using water-in-oil-in-water (W/O/W) double emulsion, solvent evaporation technique to enhance ocular penetration and prolong ophthalmic residence of VCM. Method: Two consecutive full factorial designs (24 followed by 32) were adopted to study the effect of different formulation and process parameters on SLN formulation. The lipid type and structure, polyvinyl alcohol (PVA) molecular weight and concentration, sonication time, as well as lipid:drug ratio were studied as independent variables. The formulated SLN formulae were evaluated for encapsulation efficiency (EE%), particle size (PS), and zeta potential as dependent variables. Results: The statistically-optimized SLN formula (1:1 ratio of glyceryltripalmitate:VCM with 1% low molecular weight PVA and 1 min sonication time) had average PS of 277.25 nm, zeta potential of −20.45, and 19.99% drug encapsulation. Scanning and transmission electron micrographs showed well-defined, spherical, homogenously distributed particles. Conclusion: The present study suggests that VCM incorporation into SLNs is successfully achievable; however, further studies with different nanoencapsulation materials and techniques would be valuable for improving VCM encapsulation.

Review of vancomycin-induced renal toxicity: an update.

In recent times the use of larger doses of vancomycin aimed at curbing the increasing incidence of resistant strains of Staphylococcus aureus has led to a wider report of acute kidney injury (AKI). Apart from biological plausibility, causality is implied by the predictive association of AKI with larger doses, longer duration, and graded plasma concentrations of vancomycin. AKI is more likely to occur with the concurrent use of nephrotoxic agents, and in critically ill patients who are susceptible to poor renal perfusion. Although most vancomycin-induced AKI cases are mild and therefore reversible, their occurrence may be associated with greater incidence of end-stage kidney disease and higher mortality rate. The strategy for its prevention includes adequate renal perfusion and therapeutic drug monitoring in high-risk individuals. In the near future, there is feasibility of renoprotective use of antioxidative substances in the delivery of vancomycin.

Microparticles based on chitosan/carboxymethylcellulose polyelectrolyte complexes for colon delivery of vancomycin

The aim of this work was to prepare polyelectrolyte complexes based on chitosan (CH) and carboxymethylcellulose (CMC) for colon delivery of vancomycin (VM). Various batches of polyelectrolyte complexes, using three different CH/CMC weight ratios (3:1, 1:1 and 1:3), were prepared and collected as microparticles by spray-drying process. Microparticles were characterized in terms of yield, encapsulation efficiency, drug loading, morphology and mucoadhesion properties. Microparticles water-uptake and VM release as well as its protection against gastric pepsin degradation were also investigated. Finally, the antibacterial activity against Staphylococcus aureus, a Gram-positive model strain, was evaluated. The best formulation CH/CMC 1:3 was selected based on the encapsulation efficiency, water-uptake and drug release rate. Moreover, microparticles were able to prevent VM degradation and showed a good antibacterial activity against S. aureus. Finally, to improve the release of VM in the colon the selected formulation was coated with lauric acid.

Controlled Delivery of Vancomycin via Charged Hydrogels.

Surgical site infection (SSI) remains a significant risk for any clean orthopedic surgical procedure. Complications resulting from an SSI often require a second surgery and lengthen patient recovery time. The efficacy of antimicrobial agents delivered to combat SSI is diminished by systemic toxicity, bacterial resistance, and patient compliance to dosing schedules. We submit that development of localized, controlled release formulations for antimicrobial compounds would improve the effectiveness of prophylactic surgical wound antibiotic treatment while decreasing systemic side effects. Our research group developed and characterized oligo(poly(ethylene glycol)fumarate) / sodium methacrylate (OPF/SMA) charged copolymers as biocompatible hydrogel matrices. Here, we report the engineering of this copolymer for use as an antibiotic delivery vehicle in surgical applications. We demonstrate that these hydrogels can be efficiently loaded with vancomycin (over 500 μg drug per mg hydrogel) and this loading mechanism is both time- and charge-dependent. Vancomycin release kinetics are shown to be dependent on copolymer negative charge. In the first 6 hours, we achieved as low as 33.7% release. In the first 24 hours, under 80% of total loaded drug was released. Further, vancomycin release from this system can be extended past four days. Finally, we show that the antimicrobial activity of released vancomycin is equivalent to stock vancomycin in inhibiting the growth of colonies of a clinically derived strain of methicillin-resistant Staphylococcus aureus. In summary, our work demonstrates that OPF/SMA hydrogels are appropriate candidates to deliver local antibiotic therapy for prophylaxis of surgical site infection.

Hollow mesoporous carbon nanocarriers for vancomycin delivery: understanding the structure-release relationship for prolonged antibacterial performance.

Mono-dispersed mesoporous hollow carbon (MHC) nanospheres with comparable structures have been designed as nanocarriers for the delivery of vancomycin (Van) to inhibit bacterial growth. It is demonstrated that MHC materials possess a Van loading capacity of 861 mg g-1, much higher than that of any Van nanocarrier in previous reports. By comparing the drug loading, release and antibacterial performance of MHC nanospheres with controllable structures, it is shown that MHC with a pore size of 5.8 nm and a wall thickness of 25 nm exhibits compromising storage-release behaviour and achieves extended bactericidal activity of Van towards E. coli and S. epidermidis compared to free Van and other MHC nanocarriers. This study provides new knowledge about the rational design of carbon based nanocarriers to enhance the therapeutic efficacy of antibiotics.

Novel Bone-Targeting Agent for Enhanced Delivery of Vancomycin to Bone.

We examined the pharmacokinetic properties of vancomycin conjugated to a bone-targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT-vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome.

Injectable gellan gum-based nanoparticles-loaded system for the local delivery of vancomycin in osteomyelitis treatment.

Infection spreading in the skeletal system leading to osteomyelitis can be prevented by the prolonged administration of antibiotics in high doses. However systemic antibiotherapy, besides its inconvenience and often low efficacy, provokes numerous side effects. Thus, we formulated a new injectable nanoparticle-loaded system for the local delivery of vancomycin (Vanc) applied in a minimally-invasive way. Vanc was encapsulated in poly(l-lactide-co-glycolide) nanoparticles (NPs) by double-emulsification. The size (258 ± 11 nm), polydispersity index (0.240 ± 0.003) and surface potential (−25.9 ± 0.2 mV) of NPs were determined by dynamic light scattering and capillary electrophoresis measurements. They have a spherical morphology and a smooth topography as observed using atomic force microscopy. Vanc loading and encapsulation efficiencies were 8.8 ± 0.1 and 55.2 ± 0.5 %, respectively, based on fluorescence spectroscopy assays. In order to ensure injectability, NPs were suspended in gellan gum and cross-linked with Ca2+; also a portion of dissolved antibiotic was added to the system. The resulting system was found to be injectable (extrusion force 11.3 ± 1.1 N), reassembled its structure after breaking as shown by rheology tests and ensured required burst release followed by sustained Vanc delivery. The system was cytocompatible with osteoblast-like MG-63 cells (no significant impact on cells’ viability was detected). Growth of Staphylococcus spp. reference strains and also those isolated from osteomyelitic joints was inhibited in contact with the injectable system. As a result we obtained a biocompatible system displaying ease of application (low extrusion force), self-healing ability after disruption, adjustable drug release and antimicrobial properties.

Oral teicoplanin for successful treatment of severe refractory Clostridium difficile infection

Clostridium difficile is the leading cause of hospital-acquired diarrhoea. There is no defined protocol for treating severe Clostridium difficile infection (CDI) refractory to vancomycin or vancomycin and metronidazole combination therapy. The aim of this study was to evaluate the rate of clinical cure, time to resolution of diarrhoea and recurrence rate in patients with severe refractory CDI treated with oral teicoplanin. A one-year prospective study was carried out in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia. Patients with severe and complicated CDI who failed to respond to oral vancomycin and intravenous metronidazole combination therapy were enrolled. They were given oral teicoplanin 100 mg bi-daily. Patients were followed for recurrence for eight weeks. Nine patients with a mean age of 70.8±9.4 years were analyzed. All patients had pseudomembranous colitis, and five had complicated disease. In four patients intracolonic delivery of vancomycin was also performed in addition to oral vancomycin and intravenous metronidazole prior to initiating teicoplanin, but without improvement. After teicoplanin initiation all patients achieved clinical cure. The mean time to resolution of diarrhoea after teicoplanin introduction was 6.3±4.5 days. There was no statistically significant difference in time to resolution of diarrhoea according to initial leucocyte count, age over 65 years, the presence of ileus, complicated disease and the use of concomitant antibiotic therapy (p = 0.652, 0,652, 0.374, 0.374, and 0,548, respectively). None of the patients experienced recurrence. Oral teicoplanin might be a potential treatment for severe and complicated refractory CDI, but further studies are required.

Alendronate-decorated biodegradable polymeric micelles for potential bone-targeted delivery of vancomycin

Osteomyelitis is a bone infection disease which is caused by bacteria or other germs, and could cause serious impact on the health and working capacity of the patients. Alendronate (ALN) can chelate strongly with the calcium ion of hydroxyapatite (HA) which is commonly used to treat osteoporosis. Nanomedicine has attracted a lot of attention in that the nano-sized carrier can deliver drug molecules to specific site of interest with the aid of targeting moiety and achieve sustained release, resulting in improved therapeutic effect and reduced side effect. In this study, micelles self-assembled from poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-alendronate (PLGA-PEG-ALN) copolymer were prepared for bone-targeted delivery of vancomycin (Van). The chemical structure of PLGA-PEG-ALN was confirmed by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The formation of the nanoparticles was characterized by dynamic light scattering, transmission electronic microscopy as well as the critical micelle concentration measurement. Release profiles from the micelles revealed that the conjugation of ALN to the surface of micelle did not pose adverse effect on the drug-loading capacity and release behaviors. The cytotoxicity of Van-loaded PLGA-PEG-ALN micelles as well as the blank micelles was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay toward rat bone marrow stromal cells (rBMSCs) and human embryonic hepatocytes (L02 cells), and results showed that this Van-loaded micelle possesses appropriate cytotoxicity and is safe in the potential treatment of osteomyelitis. The in vitro affinity of PLGA-PEG-ALN micelles to the HA was also confirmed in vitro. The antibacterial effect of Van-loaded PLGA-PEG-ALN micelles was tested against Staphylococcus aureus (SA) which is the main pathogenic bacteria in osteomyelitis, and the results showed that the Van-loaded micelles can effectively inhibit the growth of SA. These results demonstrated that the PLGA-PEG-ALN micelles may be potentially used for the bone targeted delivery of Van.

Chitosan based micro- and nanoparticles for colon-targeted delivery of vancomycin prepared by alternative processing methods

The aim of this work was to prepare chitosan (CH) based particulate formulations for colon delivery of vancomycin (VM). Chitosan microparticles (MPs) and nanoparticles (NPs) loaded with VM were prepared using different CH/tripolyphosphate (TPP) molar ratios and different technological processes. In particular, nanoparticles were prepared by ionic gelation and freeze-drying to recover these particles, or, alternatively, by spray-drying method. Microparticles were prepared using a different spray-dryer. Micro- and nanoparticles were characterized in terms of size distributions by photon correlation spectroscopy (PCS), while encapsulation and drug loading efficiencies were studied using a dialysis method. Fourier Transform Infrared Spectroscopy (FT-IR) was employed to determine the surface composition of the micro- and nanoparticles respectively, and the morphologies of the developed systems were studied by scanning electron microscopy (SEM). Water uptake as well as drug release profiles were also measured. Antibacterial activity against Staphylococcus aureus, a Gram-positive model strain, was evaluated. FT-IR results suggested an electrostatic interaction between VM and CH/TPP particles. Moreover, the particles were found to hold a positive zeta-potential, indicating the presence of CH on the particle surfaces. Particle size and encapsulation efficiency were mainly influenced by the different manufacturing processes employed. Nanoparticles obtained by spray-drying showed the best results in terms of water uptake and drug release rate. Moreover, they showed a good bactericidal activity against S. aureus.

Transdermal delivery of vancomycin hydrochloride using combination of nano-ethosomes and iontophoresis: in vitro and in vivo study

This study aimed to evaluate transdermal delivery of vancomycin hydrochloride using the combination of ethosomes as an encapsulating vesicle and iontophoresis. Ethosomes were prepared and evaluated in terms of electrochemical stability. Cathodal iontophoresis of negatively charged ethosomes and anodal iontophoresis of free drug solution and positively charged vesicles were conducted. The effect of current mode, density, concentration of drug and ionic strength was studied. In vivo study was performed by inducing mediastinitis in Sprague-Dawley rats using methicillin-resistant Staphylococcus aureus as infected pathogen, the mean bacterial count was compared between groups of rats, one of the treated groups received drug intramuscularly while the other group received vancomycin using iontophoretic delivery of optimized ethosomal formula. Ethosomes showed efficient electrochemical stability, cathodal iontophoresis of negatively charged vesicle (F2) showed maximum transdermal flux (550 µg/cm2/h) compared to free drug solution and other ethosomal formulae, transdermal flux was reduced by altering current mode from continuous to ON/OFF mode, reducing current density and by using normal saline as drug solvent; on the other hand, flux was potentiated by increasing drug concentration from 25 to 75 mg/ml. In vivo study revealed that there was a significant difference in terms of bacterial count between untreated and treated groups, while there was no statistically significant difference between the I.M. vancomycin treatment and treatment conducted by iontophoretic delivery of vancomycin encapsulated in ethosomal formula. Combination between ethosomes and iontophoresis had succeeded in delivering vancomycin transdermally.

Delivery of antibiotics from cementless titanium-alloy cubes may be a novel way to control postoperative infections.

Bacterial colonisation and biofilm formation onto orthopaedic devices are difficult to eradicate. In most cases infection is treated by surgical removal of the implant and cleaning of the infected area, followed by extensive treatment with broad-spectrum antibiotics. Such treatment causes great discomfort, is expensive, and is not always successful. In this study we report on the release of vancomycin through polyethersulfone membranes from channels in cementless titanium-alloy cubes. The cubes were constructed with LaserCUSING from Ti6Al4V ELI powder. Vancomycin was released by non-Fickian anomalous (constraint) diffusion. Approximately 50% of the vancomycin was released within the first 17 h. However, sustained delivery of vancomycin for 100 h was possible by reinjecting the channels. Refillable implants may be a novel way to control postoperative infections.

Sustained release of vancomycin from novel biodegradable nanofiber-loaded vascular prosthetic grafts: in vitro and in vivo study

This study describes novel biodegradable, drug-eluting nanofiber-loaded vascular prosthetic grafts that provide local and sustained delivery of vancomycin to surrounding tissues. Biodegradable nanofibers were prepared by first dissolving poly(D,L)-lactide-co-glycolide and vancomycin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibers onto the surface of vascular prostheses. The in vitro release rates of the pharmaceutical from the nanofiber-loaded prostheses was characterized using an elution method and a high-performance liquid chromatography assay. Experimental results indicated that the drug-eluting prosthetic grafts released high concentrations of vancomycin in vitro (well above the minimum inhibitory concentration) for more than 30 days. In addition, the in vivo release behavior of the drug-eluting grafts implanted in the subcutaneous pocket of rabbits was also documented. The drug-eluting grafts developed in this work have potential applications in assisting the treatment of vascular prosthesis infection and resisting reinfection when an infected graft is to be exchanged.

A novel murine model of established Staphylococcal bone infection in the presence of a fracture fixation plate to study therapies utilizing antibiotic-laden spacers after revision surgery

Mice are the small animal model of choice in biomedical research due to the low cost and availability of genetically engineered lines. However, the devices utilized in current mouse models of implant-associated bone infection have been limited to intramedullary or trans-cortical pins, which are not amenable to treatments involving extensive debridement of a full-thickness bone loss and placement of a segmental antibiotic spacer. To overcome these limitations, we developed a clinically faithful model that utilizes a locking fracture fixation plate to enable debridement of an infected segmental bone defect (full-thickness osteotomy) during a revision surgery, and investigated the therapeutic effects of placing an antibiotic-laden spacer in the segmental bone defect.To first determine the ideal time point for revision following infection, a 0.7mm osteotomy in the femoral mid-shaft was stabilized with a radiolucent PEEK fixation plate. The defect was inoculated with bioluminescent Staphylococcus aureus, and the infection was monitored over 14days by bioluminescent imaging (BLI). Osteolysis and reactive bone formation were assessed by X-ray and micro-computed tomography (micro-CT). The active bacterial infection peaked by 5days post-inoculation, however the stability of the implant fixation became compromised by 10–14days post-inoculation due to osteolysis around the screws. Thus, day 7 was defined as the ideal time point to perform the revision surgery.During the revision surgery, the infected tissue was debrided and the osteotomy was widened to 3mm to place a poly-methyl methacrylate spacer, with or without vancomycin. Half of the groups also received systemic vancomycin for the remaining 21days of the study. The viable bacteria remaining at the end of the study were measured using colony forming unit assays. Volumetric bone changes (osteolysis and reactive bone formation) were directly measured using micro-CT image analysis. Mice that were treated with local or systemic vancomycin did not display gross pathology at the end of the study. While localized vancomycin delivery alone tended to decrease the bacterial burden and osteolysis, these effects were only significant when combined with systemic antibiotic therapy.This novel mouse model replicates key features of implant-associated osteomyelitis that make treatment extremely difficult, such as biofilm formation and osteolysis, and imitates the clinical practice of placing an antibiotic-laden spacer after infected tissue debridement. In addition, the model demonstrates the limitations of current PMMA spacers and could be an invaluable tool for evaluating alternative antimicrobial treatments for implant-associated bone infection.

Composite chitosan and calcium sulfate scaffold for dual delivery of vancomycin and recombinant human bone morphogenetic protein-2

A biodegradable, composite bone graft, composed of chitosan microspheres embedded in calcium sulfate, was evaluated in vitro for point-of-care loading and delivery of antibiotics and growth factors to prevent infection and stimulate healing in large bone injuries. Microspheres were loaded with rhBMP-2 or vancomycin prior to mixing into calcium sulfate loaded with vancomycin. Composites were evaluated for set time, drug release kinetics, and bacteriostatic/bactericidal activity of released vancomycin, induction of ALP expression by released rhBMP-2, and interaction of drugs on cells. Results showed the composite set in under 36 min and released vancomycin levels that were bactericidal to S. aureus (>MIC 8-16 μg/mL) for 18 days. Composites exhibited a 1 day-delayed release, followed by a continuous release of rhBMP-2 over 6 weeks; ranging from 0.06 to 1.49 ng/mL, and showed a dose dependent release based on initial loading. Released rhBMP-2 levels were, however, too low to induce detectable levels of ALP in W20-17 cells, due to the affinity of rhBMP-2 for calcium-based materials. With stimulating amounts of rhBMP-2 (>50 ng/mL), the ALP response from W-20-17 cells was inhibited when exposed to high vancomycin levels (1,800-3,600 μg/mL). This dual-delivery system is an attractive alternative to single delivery or preloaded systems for bone regeneration since it can simultaneously fight infection and deliver a potent growth factor. Additionally, this composite can accommodate a wide range of therapeutics and thus be customizable for specific patient needs, however, the potential interactive effects of multiple agents must be investigated to ensure that functional activity is not altered.

Tissue engineering scaffold for sequential release of vancomycin and rhBMP2 to treat bone infections

The ability of silica calcium phosphate nanocomposite (SCPC75) for the controlled sequential delivery of vancomycin (Vanc) and rhBMP2 was evaluated. Fourier transform infrared spectroscopy analyses of the SCPC75 showed an increase in the bond energy of the PO4 (-3) due to the interactions with negatively charged moieties of Vanc. Furthermore, a decrease in the bond energy of the Si-O-Si functional groups was observed after rhBMP2 adsorption. In conjunction with the differences in bond site and bond energy at the ceramic/drug interface, significant differences in drug release kinetics and bioceramic dissolution rate were found. UV-vis spectrometry showed a burst release of Vanc in the first 8 h followed by a sustained release stage for up to 28 days. ELISA showed first-order release kinetics of rhBMP2 without burst release. The rhBMP2 release from SCPC75 was associated with a significantly lower rate of Ca and a higher rate of Si dissolutions when compared with Vanc release over identical time periods. Differences in the release kinetic profiles of Vanc and rhBMP2 from the SCPC75-Vanc/SCPC75-rhBMP2 scaffolds at 70/30, 50/50, or 20/80 ratios allowed for sequential drug release profiles that could be exploited to customize doses and release duration of each drug. The released rhBMP2 significantly upregulated MC3T3-E1 expression of collagen type I, osteopontin, and osteocalcin mRNA by 12.6-, 3.3-, and 2.4-fold, respectively. The released Vanc demonstrated bactericidal effects on Staphylococcus aureus in vitro. These results suggest the potential of SCPC75-Vanc-rhBMP2 scaffolds in the treatment of damaged and/or infected bone.

A novel injectable borate bioactive glass cement for local delivery of vancomycin to cure osteomyelitis and regenerate bone

Osteomyelitis (bone infection) is often difficult to cure. The commonly-used treatment of surgical debridement to remove the infected bone combined with prolonged systemic and local antibiotic treatment has limitations. In the present study, an injectable borate bioactive glass cement was developed as a carrier for the antibiotic vancomycin, characterized in vitro, and evaluated for its capacity to cure osteomyelitis in a rabbit tibial model. The cement (initial setting time=5.8±0.6min; compressive strength=25.6±0.3MPa) released vancomycin over ~25days in phosphate-buffered saline, during which time the borate glass converted to hydroxyapatite (HA). When implanted in rabbit tibial defects infected with methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis, the vancomycin-loaded cement converted to HA and supported new bone formation in the defects within 8weeks. Osteomyelitis was cured in 87% of the defects implanted with the vancomycin-loaded borate glass cement, compared to 71% for the defects implanted with vancomycin-loaded calcium sulfate cement. The injectable borate bioactive glass cement developed in this study is a promising treatment for curing osteomyelitis and for regenerating bone in the defects following cure of the infection.

Colonic decompression and direct intraluminal medical therapy forClostridium difficile-associated megacolon using a tube placed endoscopically in the proximal colon

Urgent colectomy for severe Clostridium difficile infection can be associated with increased morbidity and mortality. We aimed to use endoscopic methods for treatment. We describe a technique of placing an intracolonic tube facilitating decompression and direct delivery of vancomycin to the proximal colon along with enemas on a regular and frequent basis that may not be possible with vancomycin enemas alone. Successful resolution of the C. difficile infection and avoidance of surgery. While further long-term evaluation is required, our initial results have shown it to be effective in treating select patients with recalcitrant Clostridium difficile-associated megacolon.

A Novel Injectable Borate Bioactive Glass Cement as an Antibiotic Delivery Vehicle for Treating Osteomyelitis

BackgroundA novel injectable cement composed of chitosan-bonded borate bioactive glass (BG) particles was evaluated as a carrier for local delivery of vancomycin in the treatment of osteomyelitis in a rabbit tibial model.Materials and MethodsThe setting time, injectability, and compressive strength of the borate BG cement, and the release profile of vancomycin from the cement were measured in vitro. The capacity of the vancomycin-loaded BG cement to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in rabbit tibiae in vivo was evaluated and compared with that for a vancomycin-loaded calcium sulfate (CS) cement and for intravenous injection of vancomycin.ResultsThe BG cement had an injectability of >90% during the first 3 minutes after mixing, hardened within 30 minutes and, after hardening, had a compressive strength of 18±2 MPa. Vancomycin was released from the BG cement into phosphate-buffered saline for up to 36 days, and the cumulative amount of vancomycin released was 86% of the amount initially loaded into the cement. In comparison, vancomycin was released from the CS cement for up 28 days and the cumulative amount released was 89%. Two months post-surgery, radiography and microbiological tests showed that the BG and CS cements had a better ability to eradicate osteomyelitis when compared to intravenous injection of vancomycin, but there was no significant difference between the BG and CS cements in eradicating the infection. Histological examination showed that the BG cement was biocompatible and had a good capacity for regenerating bone in the tibial defects.ConclusionsThese results indicate that borate BG cement is a promising material both as an injectable carrier for vancomycin in the eradication of osteomyelitis and as an osteoconductive matrix to regenerate bone after the infection is cured.