Local Application Of Vancomycin Research Articles

Polycaprolactone-Coated Alginate/b-Tricalcium Phosphate Beads to Locally Deliver Vancomycin: A Pilot Study

Orthopedic device-related infections (ODRI) are difficult to control and the management of ODRI most frequently includes surgery and long-term antimicrobial therapy. Local application of vancomycin through a biodegradable carrier like alginate would provide a valuable tool, although it is hard to control the drug-release for a prolonged period of time due to its permeability. Coating with hydrophobic polymer such as polycaprolactone (PCL) may sustain the vancomycin release. We fabricated four types of vancomycin containing alginate/b-TCP beads (uncoated, coated with 1.25 w/v%, 2.5 w/v%, and 5.0 w/v% PCL). Scanning electron microscope (SEM) revealed that b-TCP particles were uniformly distributed on the surface of the uncoated beads and the most homogenous coating layer was observed using 2.5 w/v% PCL. Vancomycin release and its bioactivity were measured at the designated time points (1, 4, 12, 24 hours, then every day until disintegration). Burst release occured on the first hour, day 1, 2 and 6 respectively. The beads without coating dissolved at day 3, and those with different coatings dissolved at day 5, 6, and 9. The minimum concentration of the vancomycin in the elution was approximately 5 mg/L, higher than the vancomycin’s minimum inhibitory concentrations (MICs) for Methicillin-resistant Staphylococcus aureus (MRSA). PCL-coated alginate/b-TCP beads loaded with vancomycin may provide a potential local drug delivery device for the adjuvant antimicrobial therapy of the ODRI.

2021 J. Leonard Goldner Award Winner: Vancomycin Topically Applied at the Surgical Site Does Not Impair Diabetic Fracture Healing and Dose-Dependently Inhibits Calcified Tissue Formation by Osteoblast Precursors Cells

Category:Diabetes; Basic Sciences/Biologics; TraumaIntroduction/Purpose:Prophylactic vancomycin treatment decreases the rates of surgical site and deep infections by >70% for diabetic patients undergoing reconstructive foot and ankle surgery. We aimed to identify whether local vancomycin at a clinically relevant dose impaired fracture healing in diabetic rats. Our hypothesis was that local vancomycin powder to the fracture site would not affect long term healing outcomes, but continuous exposure of vancomycin would inhibit differentiation of osteoblast precursor cells and their osteogenic activity in vitro. The 25 mg/kg vancomycin was a modest increase to routine surgical site vancomycin application of 1-2 grams for a 70 kg. adult (21.42 mg/kg). Determining how vancomycin affects diabetic fracture healing is of clinical interest, particularly considering its prophylactic use in foot and ankle patients.Methods:Following induction of a femur fracture in male BB Wistar type 1 diabetic rats, a longitudinal incision was made in the lateral aspect of the femur. Powdered vancomycin (25mg/kg) was administered to fracture site of treated (n=5), and Sham surgery (n=6) control rats. Femurs harvested at 6 weeks after fracture, were X-ray scored, µCT scanned and tested to failure in torsion. Bone marrow and periosteal cells isolated from diabetic bones and MC3T3 cells were plated for MTT survival and osteogenic assays. After 4 days, beta glycerol phosphate, ascorbic acid and either 0, 50, 500, or 5,000 µg/mL vancomycin were added to the media (n=3 per group). Cells were fixed at 7 and 14 days for alkaline phosphatase (ALP) staining and at 28 days for Alizarin Red S staining. Parametric data were analyzed using student t-tests. Non-parametric data were analyzed using a Kruskal-Wallis ANOVA on RANKs and Tukey post-hoc tests.Results:Radiographic scoring did not show differences between the control (2.28+-1.57) and treatment (3.67+-0.75) groups (p=0.093). BV/TV was similar between the control (61.2+-8.4 %) and treatment (56.5+-5.2 %) groups (p=0.081). Mechanical testing found similar values in normalized torque to failure (69.56+-36.80 vs 50.05+-28.82 %N*mm, p=0.356), and torsional rigidity (105.97+-103.62 vs 48.68+-32.95 %Nmm2, p=0.291), for control and treatment groups, respectively. ALP staining was comparable between groups at either 7 (p=0.809) or 14 days (p=0.343) in bone marrow or MC3T3 cells. Alizarin Red S staining found dose- dependent decreases in mineralized nodule formation between the untreated (10.16+-5.01 nodules per 3.8cm2), and 500µg/mL vancomycin (3.16+-2.26 nodules per 3.8cm2) bone marrow groups at 28 days (p=0.026). Periosteal and MC3T3 cell viability were only impaired at the 5000µg/mL vancomycin dose (p=0.001).Conclusion:Our study argues that local application of vancomycin does not affect diabetic fracture healing at clinically relevant doses. We studied a nearly 2-fold higher vancomycin dose than the 'standard' dose of 14.3mg/kg and less than the 143.5mg/kg dose that did not impair rat spine fusion. Although in vitro vancomycin did not affect cell viability and osteogenic staining in periosteal and MC3T3 cells, mineralized nodule formation was dose-dependently inhibited at day 28 in bone marrow cells. Our results bring novel insight into the effects of vancomycin in diabetic fracture healing and the how long-term dosing impacts cell viability and osteoblastogenesis.

Local Application of Vancomycin in One-Stage Revision of Prosthetic Joint Infection Caused by Methicillin-Resistant Staphylococcus aureus.

The rate of eradication of periprosthetic joint infection (PJI) caused by methicillin-resistant Staphylococcus aureus (MRSA) is still not satisfactory with systemic vancomycin administration after one-stage revision arthroplasty. This study aimed to explore the effectiveness and safety of intraarticular (IA) injection of vancomycin in the control of MRSA PJI after one-stage revision surgery in a rat model. Two weeks of intraperitoneal (IP) and/or IA injection of vancomycin was used to control the infection after one-stage revision surgery. The MRSA PJI rats treated with IA injection of vancomycin showed better outcomes in skin temperature, bacterial counts, biofilm on the prosthesis, serum α1-acid glycoprotein levels, residual bone volume, and inflammatory reaction in the joint tissue, compared with those treated with IP vancomycin, while the rats treated with IP and IA administration showed the best outcomes. However, only the IP and IA administration of vancomycin could eradicate MRSA. Minimal changes in renal pathology were observed in the IP and IP plus IA groups but not in the IA group, while no obvious changes were observed in the liver or in levels of serum markers, including creatinine, alanine aminotransferase, and aspartate aminotransferase. Therefore, IA use of vancomycin is effective and safe in the MRSA PJI rat model and is better than systemic administration, while IA and systemic vancomycin treatment could eradicate the infection with a 2-week treatment course.

LOCAL VANCOMYCIN IN PREVENTION OF SURGICAL SITE INFECTION IN SPINAL SURGERIES

Background: SSIs can lead to greater post-operative morbidity, mortality and healthcare costs. Despite current prophylactic measures, SSIs is still being reported in patients undergoing spine surgery. Local application of vancomycin in spine surgery is a low-cost strategy to help reduce SSIs as it is active against pathogens which might contaminate the wound during spinal surgery.Aim of the Work: A systematic review discussing the effect of Local vancomycin in prevention of surgical site in spinal surgeries.Patients and Methods: Literature search and filtration on intra- wound application of vancomycin in spinal surgeries yielded 9 studies with a total of 46,907 patients.Results: Review of the enrolled studies confirmed that intra-wound vancomycin use appears to be safe and effective for reducing postoperative SSIs in spinal surgeries with a low rate of adverse events. However, these studies use different definitions for surgical site infections and different pre-, peri- and postoperative antibiotic regimens. That is why intra wound application of vancomycin in spinal surgeries is recommended to reduce postoperative SSIs and further studies using standardized protocols are needed to confirm findings of the current study.Conclusion: The different follow-up periods, particularly for patients with short-term follow up, may underestimate the incidence of SSIs and adverse events especially in the vancomycin group.

Local Application of Vancomycin in Spine Surgery Does Not Result in Increased Vancomycin-Resistant Bacteria—10-Year Data

Study DesignCase-control study. ObjectivesTo analyze the microbial flora in surgical spine infections and their antibiotic resistance patterns across time and determine the correlation between vancomycin application in the wound and vancomycin-resistant microbes. Summary of Background DataPrior studies show a reduction in surgical site infections with intrawound vancomycin placement. No data are available on the potential negative effects of this intervention, in particular, whether there would be a resultant increase in vancomycin-resistant organisms or bacterial resistance profiles. MethodsAll culture-positive surgical site infections at a single institution were analyzed from 2007 to 2017. Each bacterium was assessed independently for resistance patterns. The two-tailed Fisher exact test was used to determine the correlation between vancomycin application and the presence of vancomycin-resistant bacteria, polymicrobial infections, or gram-negative bacterial infections. ResultsOne hundred and eight bacteria were isolated from 113 surgical site infections from 2007 to 2017. The most common organisms were staphylococcus with varying resistance patterns and Escherichia coli. Vancomycin-resistant Enterococcus faecium was isolated in three infections. Out of the 4,878 surgical cases from 2011 to 2017, vancomycin was placed in 48.3%, and no vancomycin in 51.7%. There were 33 infections (1.4%) in the vancomycin group and 20 infections (0.8%) in the no-vancomycin group (χ2 = 0.0521). There was no correlation between vancomycin application in the wound and vancomycin-resistant microbes (χ2 = 0.2334) and polymicrobial infections (χ2 = 0.1328). There was an increased rate of gram-negative organisms in infections after vancomycin application in the wound versus no vancomycin (χ2 = 0.0254). ConclusionsTopical vancomycin within the surgical site is not correlated with vancomycin-resistant bacteria. However, there was an increased incidence of gram-negative organisms in infections after vancomycin application in the wound versus no vancomycin. Continued surveillance with prospectively collected randomized data is necessary to better understand bacterial evolution against current antimicrobial techniques. Level of EvidenceLevel III.

Use of intrawound vancomycin powder against postoperative infection after spine surgery.

Local application of vancomycin has recently become widely used in spine surgery. However, local application is not included in the indication and has not been approved by the US Food and Drug Administration (FDA). Thus, we searched for reports with “intra wound-vancomycin” and “SSI” as keywords in the MEDLINE database, and investigated the efficacy, problems with use, and future prospects based on these reports. Intrawound vancomycin was described as effective in most of the reports, but was found to have no effect or to aggravate the condition in some reports. A toxic effect on osteoblasts due to a high local concentration was described in some reports, whereas local application was found to be safe in other studies. The amount of vancomycin used and the administration method varied among the reports. Overall, the results suggest that intrawound vancomycin is clinically effective, but this has yet to be established in a randomized controlled trial. There is a need to identify cases that should be selected for this treatment and to investigate the dose and optimum concentration of vancomycin for clinical use.

Local Application of Vancomycin in Spine Surgery Does Not Result in Increased Vancomycin Resistance

Local Application of Vancomycin in Spine Surgery Does Not Result in Increased Vancomycin Resistance

Intrawound Vancomycin Powder Reduces Surgical Site Infections in Posterior Cervical Fusion

Retrospective comparative study using prospectively collected data. To compare the rate of infection with and without the use of vancomycin powder application during posterior cervical instrumentation. Surgical site infections (SSI) are a significant source of morbidity in multilevel posterior-instrumented fusions for cervical spondylotic myelopathy (CSM). Local delivery of antibiotics has been associated with decreased rates of SSI in posterior-instrumented fusions, but no study has addressed the effects of these measures on a population composed of exclusively multilevel posterior cervical instrumentation performed with decompression for CSM. All patients undergoing multilevel posterior decompression and instrumentation for CSM by a single surgeon from 2003-2011 were included. Post hoc analysis of prospectively collected data was analyzed comparing consecutive patients treated without the use of vancomycin powder with those treated after the initiation of vancomycin powder prophylaxis. Intervention cohort and controls were examined for differences in SSI rate, body mass index, neurological status, comorbidities, and complications. A total of 112 patients were included in the study. Intervention (n = 40) and control (n = 72) groups were statistically similar with regard to age, body mass index, comorbidities, estimated blood loss, and operative time. Univariate analysis showed a significant decrease in infection rate in the intervention group (0%) compared with the control group (15%) in this high-risk population (P = 0.007; power = 81%). No adverse events were noted in the intervention group associated with the use of vancomycin powder. The local application of vancomycin was associated with a significant reduction in the risk of SSI in multilevel posterior cervical-instrumented fusions for CSM. This study supports the growing body of evidence that vancomycin powder placed in the wound can reduce the incidence of postoperative wound infections, and is the first that addresses this specific population. 2.

Osteitisbehandlung an Unterschenkeln mit Knochenersatzmaterial als lokalem Antibiotikumträger

A seriously injured tsunami victim with complicated osteomyelitis is presented. The patient was treated with a new resorbable bone substitute, which can be loaded with different antibiotics. The successful treatment is illustrated by the clinical, radiological and histological features. Bilateral open fractures of the lower leg with open elbow fracture led to a bilateral amputation of the lower legs and the right arm because of a beginning sepsis. The following intramedullary osteitis with multiresistant Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecium was treated with the bone substitute PerOssal combined with systemic and local application of vancomycin and systemic application of ceftazidime and meropenem. This case report illustrates the concept of an additional local antibiotic treatment of osteomyelitis by a bone substitute also functioning as a drug delivery system.