Application Of Vancomycin Research Articles

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.

Effect of Local Delivery of Vancomycin and Tobramycin on Bone Regeneration.

ObjectiveA bone defect rat model was established to investigate the osteogenic effect of local delivery two antibiotics (vancomycin and tobramycin powder) on bone regeneration.MethodsTwenty‐four Sprague–Dawley (SD) male rats (6 to 8 weeks, 200 to 250 g) were used in this study. All these rats were randomly divided into four groups. Based on dose conversion between rat and human via body surface area, the rat dose of two antibiotics was 88μg/g and 176 μg/g for vancomycin and tobramycin, respectively. Con group (no antibiotic), Van group (vancomycin, 88 μg/g), Tob group (tobramycin 176 μg/g), and Van+Tob group (vancomycin 88μg/g combined with tobramycin 176 μg/g). A 5.0‐mm full‐thickness standardized mandibular bone defect was performed with a drill in each rat and different antibiotic powders were placed over the bone defect space, respectively. All these animals were sacrificed after 12 weeks post‐operation. The mandible bones were harvested for further radiographic and histologic analysis. The bone volume/total volume (BV/TV) ratio, bone volume (BV), and bone fractional area (BFA) in the defect area via micro‐computed tomography (μCT scanning) were further analyzed. Then, we performed a histological assessment via hematoxylin and eosin (H&E) and Masson's trichrome staining to analyze bone regeneration and also analyze the number of osteoblasts per filed.ResultsThere were no postoperative deaths, signs of vancomycin‐related or tobramycin‐related toxicity, or signs of systemic illness in any of the four groups. All wounds healed well, and no complications or surgical site infection were observed in all rats. From the μCT scans analyses, there was less bone regeneration in the Van group than in the Con group (BV/TV: F = 64.29, R 2 = 0.9602; P = 0.0052; BFA: F = 76.17, R 2 = 0.9662, P = 0.0007; BV: F = 194.4, R 2 = 0.9865, P = 0.0022). However, when the tobramycin and vancomycin were combined, an increase in bone defect re‐ossification was found in the Van+Tob group than in the Van group (BV/TV: F = 64.29, R 2 = 0.9602, P = 0.0033; BFA: F = 76.17, R 2 = 0.9662, P = 0.0006; BV: F = 194.4, R 2 = 0.9865, P = 0.0033). Routine H&E and Masson staining supported the finding of μCT scanning. Quantitative indices confirmed that both the bone regeneration and the number of osteoblasts per filed in the defect area was higher in the Van+Tob group than in the Van group (percentage of bone tissue: F = 145.7, R 2 = 0.9562, P = 0.0008; number of osteoblasts per file; F = 67.3, R 2 = 0.9098, P < 0.0001). There was no significant difference between the Con group and the Van+Tob group on the number of osteoblasts each field (F = 145.7, R 2 = 0.9562, P > 0.9999).ConclusionFor bone defect, local application of vancomycin combined with tobramycin was recommended over vancomycin alone. This animal study presents data suggesting that the use of local delivery of vancomycin and tobramycin should be investigated further in clinical studies.

Outcomes and Nephrotoxicity Associated with Vancomycin Treatment in Patients 80 Years and Older.

PurposeThis retrospective observational study investigated the efficacy and safety of vancomycin to treat patients aged 80 years and older. In particular, the associations between vancomycin trough concentration (VTC) and treatment outcomes or nephrotoxicity were explored.Patients and MethodsPatients aged ≥80 years had received ≥3 vancomycin treatments and ≥1 detection of VTC. Treatment outcomes were defined as success or failure. Nephrotoxicity was considered an increase in serum creatinine ≥ 44.2 mmol/L, or 50% above baseline, for ≥2 consecutive days. Univariate and multivariate analyses were performed to identify risk factors for treatment failure and nephrotoxicity.ResultsOf 349 patients, 120 (34.4%) experienced treatment failure. For patients with VTCs at <10, 10–15, 15–20, and ≥20 µg/mL, the clinical response rates were, respectively, 77.8, 77.0, 80.5, and 61.0%; the 30-day mortality rates were 2.8, 15.0, 15.3, and 37.8%; and the rates of persistent bacteremia were 16.7, 12.4, 11.9, and 11.0%. The multivariate analysis indicated that blood urea nitrogen ≥11 g/dL and heart failure were independently associated with treatment failure; but not VTC (P = 0.004, 0.016, 0.828, respectively). During vancomycin treatment, 42 (12.0%) patients experienced nephrotoxicity with recovery time 7.5 ± 4.5 days. Fewer than half of patients with nephrotoxicity recovered after suspending vancomycin application. The variables found independently associated with increased nephrotoxicity were: VTC ≥15 µg/mL; treatment duration ≥15 d; and concomitant aminoglycosides administration (P = 0.024, 0.035, 0.029).ConclusionIn patients aged 80 years and older, elevated VTC level was not associated with favorable treatment outcomes. Patients with VTC ≥20 µg/mL appear to suggest a worsened prognosis compared with lower VTCs. The risk of nephrotoxicity increases with elevated VTC, longer treatment time, and concomitant aminoglycoside administration.

Use of Tropical Vancomycin in Decreasing the Incidence of Surgical Site Infection in Open Heart Surgery

Aim: To study the effect of vancomycin tropically in decreasing the incidence of sternal wound infection in patients undergoing open cardiac surgery. Study design: Randomized controlled trial Place and duration: Department of Cardiovascular &amp; Thoracic Surgery Sheikh Zayed Hospital Lahore from 1st January 2019 to 31st July 2020. Methods: A total of 180 male and female planned for elective open heart surgery is selected for this research work. All patients age is between 40 and 70 years and these patients are bifurcated in two groups. In Group I there are 90 patients in which vancomycin is used on the sternal edges, while in Group II there are 90 patients in which only normal saline wash is used at the time of sternal approximation. At the end incidence of sternal wound infection is monitored to establish the benefits of tropical vancomycin. Results: One hundred and thirty three (73.89%) were males and 47 (26.11%) were females. Topical vancomycin group has decreased rate of superficial and deep sternal wound infections as compared to the patients in which topical vancomycin is not applied (2.22% vs 6.67%) and (1.11% vs 4.4%). Conclusion: Application of vancomycin tropically at surgical site at the time of closure of sternum in conjunction with prophylactic use of antibiotics reduces wound infection in open heart surgery. Keywords: Open heart surgery, Vancomycin, Sternal wound infection

Intrawound vancomycin application after spinal surgery: a propensity score-matched cohort analysis.

Surgical site infection (SSI) following spine surgery is associated with increased morbidity and healthcare costs. In an effort to reduce SSI rates, the application of intrawound vancomycin powder has gained popularity. However, there is limited high-quality evidence to support the safety and efficacy of this practice. The authors sought to determine if intrawound application of vancomycin powder improves 90-day overall SSI rates. The authors performed a retrospective, vancomycin exposure-matched cohort study at a single tertiary care hospital over 21 months. They included all patients undergoing elective spinal surgery and stratified the patients into two groups: those who received intrawound vancomycin powder application and those who received no application of vancomycin powder. The primary outcome of interest was the 90-day overall SSI rate. Secondary outcomes included rates of superficial SSI, deep SSI, wound disruption, and a post hoc analysis of the microbiology and minimum inhibitory concentrations. Baseline patient demographics, clinical presentation, comorbidities, perioperative factors, and 90-day postoperative outcomes were manually abstracted from patient charts. To mitigate bias, we performed 1:1 matching after calculating propensity scores and identified 1 patient from the no-vancomycin cohort for each patient in the vancomycin cohort. A total of 997 patients met our inclusion criteria (473 patients receiving vancomycin and 524 patients not receiving vancomycin). Propensity score matching produced 221 matched pairs. Risk-adjusted analysis demonstrated similar overall SSI rates between the groups (OR 1.9, p = 0.329). On unadjusted analysis, the overall 90-day SSI rate was greater in the vancomycin group (n = 10 [4.5%]) than in the no-vancomycin group (n = 5 [2.3%]) (p < 0.001), as were the superficial SSI rate (7 [3.2%] vs 4 [1.8%], p < 0.001), deep SSI rate (3 [1.4%] vs 1 [0.5%], p < 0.001), and wound disruption rate (5 [2.3%] vs 1 [0.5%], p < 0.001). No cultured isolate demonstrated vancomycin resistance. The authors observed no difference in SSI rates after the intrawound application of vancomycin powder during spine surgery. Vancomycin use did not contribute to antimicrobial resistance; however, it may select out gram-negative bacteria and increase rates of wound disruption.

In vitro evaluation of antibacterial efficacy of vancomycin-loaded suture tapes and cerclage wires

Usage of implants containing antibiotic agents has been a common strategy to prevent implant related infections in orthopedic surgery. Unfortunately, most implants with microbial repellent properties are characterized by accessibility limitations during daily clinical practice. Aim of this in vitro study was to investigate whether suture tapes and cerclage wires, which were treated with vancomycin, show a sustainable antibacterial activity. For this purpose, we used 24 stainless steel wire cerclages and 24 ultra-high molecular weight polyethylene and polyester suture tape test bodies. The test bodies were incubated for 30 min. in 100 mg/ml vancomycin solution or equivalent volumes of 0.9% NaCl. After measuring the initial solution uptake of the test bodies, antibacterial efficacy via agar diffusion test with Staphylococcus aureus and vancomycin elution tests were performed 1, 2, 3, and 6 days after incubation. Vancomycin-loaded tapes as well as vancomycin-loaded cerclage wires demonstrated increased bacterial growth inhibition when compared to NaCl-treated controls. Vancomycin-loaded tapes showed an additional twofold and eightfold increase of bacterial growth inhibition compared to vancomycin-loaded wires at day 1 and 2, respectively. Elution tests at day 1 revealed high levels of vancomycin concentration in vancomycin loaded tapes and wires. Additionally, the concentration in vancomycin loaded tapes was 14-fold higher when compared to vancomycin loaded wires. Incubating suture tapes and cerclage wires in vancomycin solution showed a good short-term antibacterial activity compared to controls. Considering the ease of vancomycin application on suture tapes or wires, our method could represent an attractive therapeutic strategy in biofilm prevention in orthopedic surgery.

Low post-arthroplasty infection rate is possible in developing countries: long-term experience of local vancomycin use in Iran

BackgroundUtilizing intrawound vancomycin powder in TKA surgery has yielded rather contrasting results in the current literature. Furthermore, CDC criteria, although effective in general, are not specifically designed for post-TKA infections. Here, we present a 7-year experience of vancomycin use in primary TKA in a high-volume tertiary knee center in Iran. Also, new criteria are proposed to detect suspected superficial post-TKA infections.MethodsThis is a retrospective analysis of primary total knee arthroplasties performed in a tertiary knee center, from March 2007 to December 2018, by a single senior knee surgeon. All patients with follow-up periods of less than 1 year were excluded from the study. Since March 2011, all patients received vancomycin (powder, 1 g) before water-tight closure of the joint capsule. A comparison was made between this group and historical control subjects (operated from March 2007 to March 2011).ResultsAltogether, 2024 patients were included in the study. The vancomycin and the control groups included 1710 and 314 cases respectively. Patients were mostly women (male to female ratio, 1 to 4), with a mean age of 65.20 (SD = 10.83) years. In the vancomycin group, the rate of suspected SII (1.87%) and PJI (0.41%) was significantly lower than the control group (P = 0.002).ConclusionsOur experience shows that application of local vancomycin during TKA surgery could be a reasonable infection prevention measure, although prospective randomized studies are required to evaluate its efficacy.

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.

Efficacy of prophylactic application of vancomycin powder in preventing surgical site infections after instrumented spinal surgery: A retrospective analysis of patients with high-risk conditions.

This study aimed to determine the efficacy of prophylactic use of vancomycin powder against surgical site infections in patients with high-risk conditions who underwent posterior spinal instrumentation. Data obtained from 209 patients who underwent posterior spinal instrumentation at a single institution from 2014 to 2017 were retrospectively reviewed. Patients were then divided into two groups: control group, including 107 patients (61 females, 46 males; mean age=54 years; age range=16-85 years), and treatment group, including 102 patients (63 females, 39 males; mean age=53 years; age range=14-90 years). All patients received the same standard prophylactic antibiotic regimen. In addition to the prophylactic antibiotic, vancomycin powder was applied locally to the surgical site in the treatment group. All patients were followed up for at least 90 days postoperatively. Infections were categorized as superficial and deep infections. Subgroup analysis of high-risk patients (Syrian refugees) was also performed. The infection rates were 1.96% (two patients) in the treatment group and 6.54% (seven patients) in the control group. A significant decrease in the infection rates was observed with local vancomycin powder application. Advanced age (>46 years) and prolonged surgical duration (>140 min) were found to be the main risk factors for surgical site infections (p=0.004 and p=0.028, respectively). The infection rates were 3.22% and 8.11% in the treatment and control groups of refugees, respectively. There were three superficial and four deep infections in the control group and one superficial and one deep infection in the treatment group. A dominance of staphylococcus infections was observed in the control group, whereas no significant dominance was observed in the treatment group. Three patients in the control group and one patient in the treatment group received implant removal. Evidence from this study has revealed that local application of vancomycin powder reduces the rate of surgical site infections after instrumented spinal surgery. The benefit of vancomycin application may be most appreciated in higher risk populations or in clinics with high baseline rates of infection. Level III, Therapeutic Study.

Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units

Management of vancomycin administration for intensive care units (ICU) patients remains a challenge. The aim of this study was to describe a population pharmacokinetic model of vancomycin for optimizing the dose regimen for ICU patients. We prospectively enrolled 466 vancomycin-treated patients hospitalized in the ICU, collected trough or approach peak blood samples of vancomycin and recorded corresponding clinical information from July 2015 to December 2017 at Tai Zhou Hospital of Zhejiang Province. The pharmacokinetics of vancomycin was analyzed by nonlinear mixed effects modeling with Kinetica software. Internal and external validation was evaluated by the maximum likelihood method. Then, the individual dosing regimens of the 92 patients hospitalized in the ICU whose steady state trough concentrations exceeded the target range (10–20 μg/ml) were adjusted by the Bayes feedback method. The final population pharmacokinetic model show that clearance rate (CL) of vancomycin will be raised under the conditions of dopamine combined treatment, severe burn status (Burn-S) and increased total body weight (TBW), but reduced under the conditions of increased serum creatinine (Cr) and continuous renal replacement therapy status; Meanwhile, the apparent distribution volume (V) of vancomycin will be enhanced under the terms of increased TBW, however decreased under the terms of increased age and Cr. The population pharmacokinetic parameters (CL and V) according to the final model were 3.16 (95%CI 2.83, 3.40) L/h and 60.71 (95%CI 53.15, 67.46). The mean absolute prediction error for external validation by the final model was 12.61% (95CI 8.77%, 16.45%). Finally, the prediction accuracy of 90.21% of the patients’ detected trough concentrations that were distributed in the target range of 10–20 μg/ml after dosing adjustment was found to be adequate. There is significant heterogeneity in the CL and V of vancomycin in ICU patients. The constructed model is sufficiently precise for the Bayesian dose prediction of vancomycin concentrations for the population of ICU Chinese patients.

Circulatory collapse during wound closure in spine surgery with an unknown cause: a possible adverse effect of topical application of vancomycin?

BackgroundVancomycin (VCM) is effective in fighting Gram-positive bacteria related severe infections, and topical application of VCM powder is widely used in orthopedic surgery to prevent wound infection. However, VCM could lead to infusion rate-dependent antibody-and complement-independent anaphylaxis reaction by inducing direct release of histamine.Case presentationWe retrospectively analyzed seven cases of severe hypotension and shock during wound closure or immediately after orthopedic surgery with unidentifiable reasons. We found that these cases were all associated with local application of VCM powder during wound closure process. Two patients experienced sudden cardiac arrest. Most of the cases (6/7) with circulatory collapse were discharged without severe sequelae. While one case with application of 3 g VCM developed cardiac arrest and remained in a coma due to hypoxic-hypoxic encephalopathy. The clinical presentations and the time of the shock onset were considered to be related with a VCM induced anaphylaxis reaction. However, as this was a retrospective study, and there was no laboratory examination performed, the conclusion was made upon differential diagnosis based on clinical manifestations and the timing of the shock.ConclusionsLocal application of VCM may not be as safe as was once believed and may lead to a related anaphylaxis. As VCM induced infusion-rate dependent, non-IgE mediated anaphylaxis is characterized by delayed occurrence, severe hypotension and even circulatory collapse, surgeons and anesthesiologists should be extra vigilant during and after VCM application.

Control of Vancomycin Activity through the Encapsulation and Controlled Release from a Propargyl Acrylate-Poloxamer Nanocomposite System.

Vancomycin is a potent antibacterial drug that suffers from poor bioavailability due to its poor water solubility and relatively high molecular weight. Consequently, the application of vancomycin to treat bacteria-induced disease is limited. In this study, the ability of a temperature-stimulated propargyl acrylate-poloxamer nanocomposite (PAPN) system to encapsulate and release vancomycin is investigated. A controllable encapsulation and release system can be used to not only increase and prolong the bioavailability of vancomycin but also activate vancomycin with a temperature change. The PAPN system was prepared using an emulsion polymerization of propargyl acrylate followed by a surface decoration with a poloxamer at a precisely controlled grafting density. The activity of the PAPN system loaded with vancomycin is compared to that of the free drug and unmodified propargyl acrylate nanoparticles. It is shown that the activity of the PAPN system loaded with vancomycin is comparable to that of a freshly prepared, free-floating vancomycin solution. Upon storage, the activity of the free vancomycin in solution decreases, while the PAPN system loaded with vancomycin retains its high activity. Additionally, the PAPN system is able to effectively encapsulate and deactivate vancomycin until heated above a lower critical solution temperature (LCST). At temperatures above the LCST, the PAPN system releases vancomycin restoring the activity of the drug.

Population Pharmacokinetic Study of Vancomycin in Chinese Pediatric Patients with Hematological Malignancies.

Vancomycin is a primary antibiotic for the treatment of severe infections in children with malignant hematological disease. However, precise dosing of vancomycin is difficult in children because of high interindividual variability and limited data of pharmacokinetic profiles. The present study aims to develop a population pharmacokinetic (PPK) model for vancomycin in Chinese pediatric patients with hematological malignancies. This was a retrospective pharmacokinetic study. The setting for this study was a tertiary-care children's hospital. This study included 92 pediatric patients with hematological malignancies who received vancomycin and experienced therapeutic drug monitoring from February 2017 to December 2018. A PPK model was generated with a nonlinear mixed effects model. In addition, required doses to achieve target therapeutic concentrations were simulated based on the final model. A one-compartment model with first-order elimination fit the concentration data best. Actual body weight (BW) and glomerular filtration rate (GFR) were the significant influential factors on the clearance (CL) of vancomycin. The final PPK model for CL was CL (L/h)=4.18 , K= , and the volume of distribution was 22.3L. The model proved to be robust and reliable. Reference dosing regimens were proposed based on the final model. A PPK model of vancomycin was established for Chinese pediatric patients with hematological malignancies using a nonlinear mixed effects model, which provided a reference for the clinical application of vancomycin.

Adverse reactions of vancomycin in humans: A protocol for meta-analysis.

Background:Vancomycin is effective against Gram-positive bacteria and considered as a last resort in the case of ineffective use of other antigens. While due to the occurrence of adverse reactions, the application of vancomycin is strictly limited. We will conduct a meta-analysis to summarize adverse reactions of vancomycin in humans.Methods:To collect comprehensive randomized controlled trials (RCTs), the following electronic databases will be searched: PubMed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database. The range of publication time will be from the inception of the database to August 2020 without language limitation. Two reviewers will independently conduct selection of studies, data extraction and management, and assessment of risk of bias. Any disagreement will be resolved by discussion with the third reviewer. Review Manager 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration) will be used for meta-analysis. The Cochrane risk of bias tool will be used to assess the risk of bias.Results:This study will synthesize the data from the present eligible high quality RCTs to explore the incidence of adverse reactions such as hypersensitivity reactions, nephrotoxicity, ototoxicity, phlebitis, and agranulocytosis.Conclusion:This meta-analysis will provide systematic evidence for adverse reactions of vancomycin in humans.Study registration number:INPLASY202080094

The Osteogenic Effect of Local Delivery of Vancomycin and Tobramycin on Bone Marrow Stromal Cells.

PurposeBone tissue infections are a difficult problem in orthopedic surgery. Topical application of vancomycin and tobramycin powder has been proved to significantly reduce infection rates. However, the osteogenic effect of the topical application of these two antibiotics is unclear. In this study, the osteogenic effect of local delivery antibiotics on bone regeneration was investigated in vitro.MethodsBone marrow stromal cells (BMSCs) were incubated in the presence of vancomycin (14.28μg/mL), tobramycin (28.57μg/mL), or vancomycin combined with tobramycin (vancomycin 14.28μg/mL and tobramycin 28.57μg/mL). Cell viability, proliferation, and migration were analyzed. The alizarin red staining as well as the alkaline phosphatase staining was investigated. Then, the quantitative real-time (qRT)-PCR of osteogenic mRNA expression levels were also evaluated.ResultsThe results showed that vancomycin combined with tobramycin has no adverse effect on the viability and proliferation of BMSCs. The topical application of vancomycin alone may interfere with the bone regenerative processes. However, the tobramycin can promote the osteogenic differentiation of BMSCs and also rescue the osteogenic potential of BMSCs inhibited by vancomycin both in vitro.ConclusionFrom this in vitro study, local application of vancomycin combined with tobramycin does not affect the osteogenic potential of BMSCs.

Combinations of (lipo)glycopeptides with β-lactams against MRSA: susceptibility insights.

Increasing application of vancomycin due to the high prevalence of MRSA infections has led to the emergence of vancomycin intermediate-resistant Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA). Consequently, the need for alternative therapies that target MRSA has become evident. To evaluate the synergy between (lipo)glycopeptides (LGP/GPs) (vancomycin, teicoplanin, telavancin, dalbavancin and oritavancin) and β-lactams (ceftaroline, cefepime, cefazolin and oxacillin) against MRSA, hVISA, VISA and daptomycin non-susceptible (DNS) phenotypes. Twenty randomly selected clinical MRSA strains (i.e. 5 MRSA, 5 hVISA, 5 VISA and 5 DNS) were assessed versus LGP/GPs alone and LGP/GPs in combination with β-lactams for MICs. Although verification of antibiotic potency against bacterial strains is assessed by the microbroth dilution (MBD) MIC method recommended by the CLSI, some antibiotics need modified assay conditions in order to demonstrate their optimal activity. Addition of β-lactams reduced MIC values of LGP/GPs against all strains (up to 160-fold reduction). In general, LGPs (dalbavancin, oritavancin and telavancin) were more active (significant differences in MIC values, up to 8-fold) compared with vancomycin and teicoplanin. The majority of these combinations were bactericidal and superior to any single agent. This report has examined the susceptibility patterns of LGP/GPs and their combination with β-lactams. Of interest, the impact of susceptibility tests (in terms of MIC plates and their surface area) on the synergistic activity in 24 h time-kill experiments was apparent for LGPs. Further clinical research is required to investigate synergy with LGP/GPs and β-lactams against these Staphylococcus strains.

Vancomycin Powder and Dilute Povidone-Iodine Lavage for Infection Prophylaxis in High-Risk Total Joint Arthroplasty

BackgroundDilute povidone-iodine lavage has been shown to be safe and effective in decreasing acute periprosthetic joint infection (PJI) following total joint arthroplasty (TJA). Vancomycin powder is reported to be effective in preventing infection in spine surgery. We hypothesize that a “vanco-povidone protocol” (VIP) for TJA patients at high risk for infection is safe and will decrease the rate of PJI. MethodsHigh-risk TJA patients (body mass index >40, active smokers, American Society of Anesthesiologists ≥3, immunosuppression/diabetes, methicillin-resistant Staphylococcus aureus colonization, revision surgery) utilizing VIP were compared to a high-risk historical cohort not treated with VIP, at a single institution. VIP consisted of dilute povidone-iodine lavage followed by application of vancomycin powder prior to wound closure. Primary endpoint was PJI within 3 months postoperatively. ResultsThe historical, high-risk control cohort consisted of 3251 patients with a PJI incidence of 1.8%. A total of 1413 subjects received the VIP protocol with a PJI incidence of 1.3%. There was a 27.8% risk reduction when compared to the control group of high-risk subjects not treated with the VIP. There were no medical complications secondary to the use of VIP, no increase in vancomycin-resistant enterococcus or vancomycin-resistant Staph aureus, and no cases of acute renal impairment secondary to application of the local vancomycin. ConclusionsPJI remains a common complication of TJA, especially in high-risk populations. This study indicates that a protocol of dilute povidone-iodine lavage combined with topical vancomycin powder is safe and may reduce PJI incidence in high-risk TJA patients. Due to low, current PJI rates, a multi-institutional randomized controlled trial is necessary to assess interventions that minimize the risk of PJI. Level of EvidenceRetrospective Observational Cohort.

Spinal Fusion Surgery and Local Antibiotic Administration: A Systematic Review on Key Points From Preclinical and Clinical Data.

Systematic review. The present review of clinical and preclinical in vivo studies focused on the local antibiotic administration for surgical site infection (SSI) in spinal fusion procedures and identifying new approaches or research direction able to release antibiotics in the infected environment. SSI is a severe complication of spinal fusion procedures that represents a challenging issue for orthopedic surgeons. SSIs can range from 0.7% to 2.3% without instrumentation up to 6.7% with the use of instrumentation with significant implications in health care costs and patient management. A systematic search was carried out by two independent researchers according to the PRISMA statement in three databases (www.pubmed.com, www.scopus.com and www.webofknowledge.com) to identify preclinical in vivo and clinical reports in the last 10 years. Additionally, to evaluate ongoing clinical trials, three of the major clinical registry websites were also checked (www.clinicaltrials.gov, www.who.int/ictrp, https://www.clinicaltrialsregister.eu). After screening, a total of 43 articles were considered eligible for the review: 36 clinical studies and seven preclinical studies. In addition, six clinical trials were selected from the clinical registry websites. The results reported that the topical vancomycin application seem to represent a strategy to reduce SSI incidence in spine surgery. However, the use of local vancomycin as a preventive approach for SSIs in spine surgery is mostly based on retrospective studies with low levels of evidence and moderate/severe risk of bias that do not allow to draw a clear conclusion. This review also underlines that several key points concerning the local use of antibiotics in spinal fusion still remains to be defined to allow this field to make a leap forward that would lead to the identification of specific approaches to counteract the onset of SSIs. 4.

Effect of topical Vancomycin on consolidation of sternum surgical fracture in open-heart surgery

Introduction: The physiological process of sternum surgical fracture consolidation in patients undergoing cardiac surgery could be prolonged by the invasion of gram-positive saprophytic bacteria which perpetuates the local inflammatory process despite the standardized aseptic and antiseptic measures in cardiac surgery. In this regard, the topical application of Vancomycin can exert a positive effect and prevent the perpetuation of the local inflammatory process by the elimination of these bacteria which in turn reduces bone consolidation time.The purpose of the current study was to determine the effect of topical Vancomycin on sternum surgical fracture consolidation in patients undergoing to open-heart surgery. Materials and Methods: Patients who underwent open heart surgery were assigned into groups receiving the topical application of bone wax or Vancomycin mass in the spongy tissue exposed by surgical sternotomy, prior to sternal closure. The bone consolidation processes were assessed by two expert radiologists with simple chest computed tomography (CT) in the postoperative period (4, 8, and 12 weeks). Results: The study was conducted on 55 patients in Vancomycin (n=33) and bone wax group (n=19). The computerized axial tomography (CAT) scan revealed a higher number of patients with early bone consolidation (Medullar and bone continuity, and callus bone) in Vancomycin group, as compared to bone wax group (p values between 0.004-0.02 at 4 weeks and 0.01-0.06 at 8 weeks). However, no difference was observed at 12 weeks (P=0.09-0.11). Moreover, The magnitude effect of topical Vancomycin was high (>90%) at 3, 8, and 12 weeks of follow up, compared to the patients who received bone wax (<90%). Conclusion: The topical Vancomycin application had a positive effect on sternal surgical fracture and promotes an early bone consolidation in patients undergoing open-heart surgery.

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.