Can local application of vancomycin reduce surgical site infection rate after open lumbar fusion surgery?: A multicenter retrospective cohort study.

Surgical site infection (SSI) after posterior open lumbar fusion (POLF) is a major concern for both surgeons and patients. We sought to explore whether local application of vancomycin could decrease the rate of SSI. We reviewed the clinical data of patients who underwent POLF between June 2015 and June 2022 at 3 spinal centers. Patients were divided into those who received local vancomycin (vancomycin group) and those who did not (non-vancomycin group). The SSI rates at 12 months postoperatively were compared between the 2 groups. Although a trend toward a lower infection rate was observed in the vancomycin group than in the non-vancomycin group; the difference was not statistically significant (3.6% vs 5.5%, P = .121). However, we found that the postoperative SSI rate was significantly lower in the vancomycin group than in the non-vancomycin group (4.9% vs 11.4%, P = .041) in patients ≥ 2 fused segments, while there was no significant difference in postoperative SSI rate in patients with single fusion segment (3.1% vs 3.6%, P = .706). The logistic regression analysis indicated that the SSI rate in the non-vancomycin group was approximately 2.498 times higher than that in the vancomycin group (P = .048, odds ratio: 2.498, 95% confidence interval: 1.011-6.617) in patients with ≥2 fused segments. In SSI patients with confirmed pathogens, the SSI rate of Gram-negative bacteria in the vancomycin group was significantly higher than that in the non-vancomycin group (10/14 [71.4%] vs 5/22 [31.8%]), whereas the SSI rate of Gram-positive bacteria in the vancomycin group was significantly lower than that in the non-vancomycin group (4/14 [28.6%] vs 15/22 [68.2%]). Local administration of vancomycin is recommended in patients with ≥2 fused segments as it may facilitate to reduce the postoperative rate of SSI after POLF. Additionally, the local use of vancomycin can decrease the Gram-positive bacterial infections but is not effective against Gram-negative infections, which indirectly leads to an increase in the proportion of Gram-negative infections in SSI patients with confirmed pathogens.

[Intraosseous vancomycin in total knee arthroplasty]. / Vancomicina intraósea en artroplastía total de rodilla.

INTRODUCTION: intravenous antibiotic prophylaxis has significantly reduced the incidence of periprosthetic joint infection (PJI) in knee surgeries. However, for patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) or those at risk of colonization, prophylaxis should include vancomycin. Intraosseous (IO) administration of vancomycin could enhance its effectiveness in total knee arthroplasty (TKA). MATERIAL AND METHODS: a retrospective review was conducted, including 143 patients at risk of PJI scheduled for TKA who received IO vancomycin along with intravenous (IV) cefazolin, referred to as group I (GI), between May 2021 and December 2022. The occurrence of complications in the first three postoperative months was evaluated. Results were compared with 140 patients without risk factors who received standard IV prophylaxis, designated as group II (GII). RESULTS: in GI, 500 mg of IO vancomycin was administered, injected into the proximal tibia, in addition to standard IV prophylaxis. In GII, patients received only IV cefazolin. The incidence of complications was 1.64% in GI and 1.4% in GII. The PJI rate at 90 postoperative days was 0.69% in GI and 0.71% in GII. CONCLUSIONS: IO vancomycin administration, along with standard IV prophylaxis, provides a safe and effective alternative for patients at risk of MRSA colonization. This approach minimizes complications associated with IV vancomycin use and addresses logistical challenges of timely administration.

INTRODUCCIÓN: la profilaxis antibiótica intravenosa ha reducido significativamente la incidencia de infección articular periprotésica (IAP) en cirugías de rodilla. No obstante, para pacientes colonizados con Staphylococcus aureus resistente a meticilina (SARM) o aquellos con riesgo de colonización, la profilaxis debe incluir vancomicina. La administración intraósea de vancomicina podría potenciar su efectividad en la artroplastía total de rodilla. MATERIAL Y MÉTODOS: se realizó una revisión retrospectiva que incluyó a 143 pacientes en riesgo de IAP programados para artroplastía total de rodilla que recibieron vancomicina intraósea junto a cefazolina intravenosa (IV), a quienes denominamos grupo I (GI), entre mayo de 2021 y diciembre de 2022. Se evaluó la aparición de complicaciones en los primeros tres meses postoperatorios. Los resultados se compararon con 140 pacientes sin factores de riesgo que recibieron profilaxis intravenosa estándar, denominados grupo II (GII). RESULTADOS: en el GI, se administraron 500 mg de vancomicina intraósea, inyectados en la tibia proximal, además de la profilaxis intravenosa estándar. En el GII, los pacientes recibieron sólo cefazolina intravenosa. La incidencia de complicaciones fue de 1.64% en el GI y de 1.4% en el GII. La tasa de IAP a los 90 días postoperatorios fue de 0.69% en el GI y de 0.71% en el GII. CONCLUSIONES: la administración de vancomicina intraósea, junto con la profilaxis intravenosa estándar, ofrece una alternativa segura y eficaz para pacientes con riesgo de colonización por SARM. Este enfoque minimiza las complicaciones asociadas con el uso intravenoso de vancomicina y soluciona los desafíos logísticos de la administración oportuna.

The effect of different preventive strategies during total joint arthroplasty on periprosthetic joint infection: a network meta-analysis.

BACKGROUND: Periprosthetic joint infection after total joint arthroplasty has a large incidence, and it may often require two or more stages of revision, placing an additional burden on clinicians and patients. The purpose of this network meta-analysis is to evaluate the effect of four different preventive strategies during total joint arthroplasty on the prevention of periprosthetic joint infection. METHODS: The study protocol was registered at PROSPERO (CRD: 42,023,448,868), and the literature search databases included Web of Science, PubMed, OVID Cochrane Central Register of Controlled Trials, OVID EMBASE, and OVID MEDLINE (R) ALL that met the requirements. The network meta-analysis included randomized controlled trials, retrospective cohort studies and prospective cohort studies with the outcome of periprosthetic joint infection. The gemtc R package was applied to perform the network meta-analysis to evaluate the relative results of different preventive strategies. RESULTS: This network meta-analysis study included a total of 38 articles with 4 preventive strategies and negative controls. No improvement was observed in antibiotic-loaded bone cement compared with negative controls. Chlorhexidine showed the highest probability of delivering the best preventive effect, and povidone iodine had the second highest probability. Although vancomycin ranked after chlorhexidine and povidone iodine, it still showed a significant difference compared with negative controls. In addition, the incidence after applying chlorhexidine was significantly lower than that after applying negative controls and vancomycin. In the heterogeneity test between direct and indirect evidence, there was no apparent heterogeneity between them. CONCLUSION: The study indicated that chlorhexidine, povidone iodine and vancomycin showed significant efficacy in preventing periprosthetic joint infection after total joint arthroplasty, while antibiotic-loaded bone cement did not. Therefore, more high-quality randomized controlled trials are needed to verify the results above.

Controlled release of vancomycin from PEGylated fibrinogen polyethylene glycol diacrylate hydrogel.

Surgical site infection (SSI) is a common issue post-surgery which often prolongs hospitalization and can lead to serious complications such as sternal wound infection following cardiac surgery via median sternotomy. Controlled release of suitable antibiotics could allow maximizing drug efficacy and safety, and therefore achieving a desired therapeutic response. In this study, we have developed a vancomycin laden PEGylated fibrinogen-polyethylene glycol diacrylate (PF-PEGDA) hydrogel system that can release vancomycin at a controlled and predictable rate to be applied in SSI prevention. Two configurations were developed to study effect of the hydrogel on drug release, namely, vancomycin laden hydrogel and vancomycin solution on top of blank hydrogel. The relationship between the rigidity of the hydrogel and drug diffusion was found to comply with a universal power law, i.e., softer hydrogels result in a greater diffusion coefficient hence faster release rate. Besides, vancomycin laden hydrogels exhibited burst release, whereas the vancomycin solution on top of blank hydrogels exhibited lag release. A mathematical model was developed to simulate vancomycin permeation through the hydrogels. The permeation of vancomycin can be predicted accurately by using the mathematical model, which provided a useful tool to customize drug loading, hydrogel thickness and stiffness for personalized medication to manage SSI. To evaluate the potential of hydrogels for bone healing applications in cardiovascular medicine, we performed a proof-of-concept median sternotomy in rabbits and applied the hydrogels. The hydrogel formulations accelerated the onset of osteo-genetic processes in rabbits, demonstrating its potential to be used in human.

Does Sample Size, Sampling Strategy, or Handling of Concentrations Below the Lower Limit of Quantification Matter When Externally Evaluating Population Pharmacokinetic Models?

BACKGROUND AND OBJECTIVES: Precision dosing requires selecting the appropriate population pharmacokinetic model, which can be assessed through external evaluations (EEs). The lack of understanding of how different study design factors influence EE study outcomes makes it challenging to select the most suitable model for clinical use. This study aimed to evaluate the impact of sample size, sampling strategy, and handling of concentrations below the lower limit of quantification (BLQ) on the outcomes of EE for four population pharmacokinetic models using vancomycin and tobramycin as examples. METHODS: Three virtual patient populations undergoing vancomycin or tobramycin therapy were simulated with varying sample size and sampling scenarios. The three approaches used to handle BLQ data were to (1) discard them, (2) impute them as LLOQ/2, or (3) use a likelihood-based approach. EEs were performed with NONMEM and R. RESULTS: Sample size did not have an important impact on the EE results for a given scenario. Increasing the number of samples per patient did not improve predictive performance for two out of the three evaluated models. Evaluating a model developed with rich sampling did not result in better performance than those developed with regular therapeutic drug monitoring. A likelihood-based method to handle BLQ samples impacted the outcomes of the EE with lower bias for predicted troughs. CONCLUSIONS: This study suggests that a large sample size may not be necessary for an EE study, and models selected based on TDM may be more generalizable. The study highlights the need for guidelines for EE of population pharmacokinetic models for clinical use.

Impact of a 20 mg/kg vancomycin loading dose on early AUC target attainment.

This retrospective chart review evaluated whether 20 mg/kg vancomycin loading doses increase early area under the curve (AUC) target attainment within 48 hours in comparison to non-loading dose regimens. There were no differences between groups for the primary outcome (46 % vs. 50 %; P = 0.58).

Vancomycin: An analysis and evaluation of eight population pharmacokinetic models for clinical application in general adult population.

INTRODUCTION: Based on the recent guidelines for vancomycin therapeutic drug monitoring (TDM), the area under the curve to minimum inhibitory concentration ratio was to be employed combined with the usage of population pharmacokinetic (popPK) model for dosing adaptation. Yet, deploying these models in a clinical setting requires an external evaluation of their performance. OBJECTIVES: This study aimed to evaluate existing vancomycin popPK models from the literature for the use in TDM within the general patient population in a clinical setting. METHODS: The models under external evaluation were chosen based on a review of literature covering vancomycin popPK models developed in general adult populations. Patients' data were collected from Charles-Le Moyne Hospital (CLMH). The external evaluation was performed with NONMEM® (v7.5). Additional analyses such as evaluating the impact of number of samples on external evaluation, Bayesian forecasting, and a priori dosing regimen simulations were performed on the best performing model. RESULTS: Eight popPK models were evaluated with an independent dataset that included 40 patients and 252 samples. The model developed by Goti and colleagues demonstrated superior performance in diagnostic plots and population predictive performance, with bias and inaccuracy values of 0.251% and 22.7%, respectively, and for individual predictive performance, bias and inaccuracy were -4.90% and 12.1%, respectively. When limiting the independent dataset to one or two samples per patient, the Goti model exhibited inadequate predictive performance for inaccuracy, with values exceeding 30%. Moreover, the Goti model is suitable for Bayesian forecasting with at least two samples as prior for the prediction of the next trough concentration. Furthermore, the vancomycin dosing regimen that would maximize therapeutic targets of area under the curve to minimum inhibitory concentration ratio (AUC24/MIC) and trough concentrations (Ctrough) for the Goti model was 20 mg/kg/dose twice daily. CONCLUSION: Considering the superior predictive performance and potential for Bayesian forecasting in the Goti model, future research aims to test its applicability in clinical settings at CLMH, both in a priori and a posteriori scenario.

[Utility of topical vancomycin application in the prevention of surgical site infection of the lumbosacral spine]. / Utilidad de la aplicación de vancomicina tópica en la prevención de infección de sitio quirúrgico de la columna lumbosacra.

INTRODUCTION: surgical site infections (SSI) remain a significant cause of morbidity and mortality and one of the most representative causes of nosocomial infections. The use of intrawound vancomycin in lumbar spine surgery is a potential prophylactic measure against SSI; however, evidence regarding its efficacy is contradictory. Our study was designed to research if intrawound vancomycin significantly prevents SSI in lumbar spine surgery. MATERIAL AND METHODS: this is a randomized, double-blinded, controlled clinical trial; 233 patients who underwent lumbar spine surgery, were randomly assigned to a group in which intrawound vancomycin was instilled in the incision before closure (109), or to a control group (114). The main outcome is the presence of SSI; we determined its prevalence and searched for difference between groups for association between SSI and independent variables. RESULTS: global SSI prevalence was 1.8%, in the experimental group was 0.9%, in the control group was 2.6%. There was no significant difference between these values, p = 0.622. The relative risk of SSI in the experimental group was 0.35 (95% CI 0.037-3.30), that of the control group was 2.87 (95% CI 0.30-27.16). The number needed to treat is 58.3. We did not find a significant association between the independent variables studied and the appearance of SSI. CONCLUSIONS: we did not find a significant difference in the prevalence of SSI between groups nor a significant association between SSI and independent variables.

INTRODUCCIÓN: las infecciones postoperatorias del sitio quirúrgico son una importante causa de morbimortalidad y una de las formas más comunes de infecciones nosocomiales. La aplicación de vancomicina al terminar una intervención de columna lumbar es una potencial práctica profiláctica de infecciones del sitio quirúrgico (ISQ). La evidencia que sostiene su uso es controversial. Nuestro estudio investiga si la aplicación de vancomicina disminuye en forma significativa la prevalencia de ISQ. MATERIAL Y MÉTODOS: ensayo clínico aleatorizado, controlado, cegado; 223 pacientes intervenidos de la columna lumbar fueron aleatoriamente asignados a un grupo experimental de 109 pacientes en quienes se colocó vancomicina y a un grupo control de 114 pacientes que no recibió vancomicina. El principal desenlace del estudio es la aparición de ISQ; se estudió la prevalencia de ISQ en ambos grupos y se buscó si existe diferencia significativa. Se analizó la existencia de factores predictores de ISQ. RESULTADOS: la prevalencia global de infección fue 1.8%; en el grupo experimenta 0.09% y en el grupo control 2.6%. No hubo diferencia significativa entre estas cifras, p = 0.622. El riesgo relativo de ISQ en el grupo experimental fue 0.35 (IC95% 0.037-3.30), el del grupo control fue 2.87 (IC95% 0.30-27.16). El número necesario para tratar es 58.3. No encontramos asociación significativa entre las variables independientes estudiadas y la aparición de ISQ. CONCLUSIONES: no encontramos evidencia suficiente de que la aplicación de vancomicina disminuya significativamente la prevalencia de ISQ ni asociación significativa de ISQ con las variables independientes estudiadas.

Limb salvage and systemic management of gouty tophi: Case series.

INTRODUCTION: Gout is a chronic disease characterized by deposition of monosodium urate crystals. Tophi develop in some individuals with untreated or uncontrolled gout, which leads to ulcerations, cosmetic problems, mechanical obstruction of joint movement, joint damage and musculoskeletal disability. Currently, the treatment of gouty tophi is controversial and challenging. Both surgical and internal medical treatments have limitations and require further exploration in clinical practice. PATIENT CONCERNS: In Case 1, we treated a patient with severe infection of diabetic foot ulcers with concomitant multiple gouty tophi in the same limb. A systematic management strategy was formulated to close the wound and save the limb. The ulcers healed successfully after half a year. In Case 2, a giant gouty tophi located in the first metatarsophalangeal joint of the left foot was removed by surgical treatment and vancomycin-loaded bone cement implantation. In Case 3, we present a case of gouty tophi that was resolved by standardized systemic medical management. DIAGNOSIS: Three patients were all diagnosed with gout accompanied by gouty deposition, although there were other different comorbidities. INTERVENTIONS: In case 1, we used debridement to gradually remove gouty tophi. In case 2, the giant gouty tophi was removed by surgical operation. In case 3, the gouty tophi disappeared after standardized treatment with medicine, diet and lifestyle management. OUTCOMES: Three patients underwent different treatment therapies to remove gouty tophi based on their specific conditions. LESSONS: We explored effective interventions for tophi in gout by surgical or other interventions in combination with pharmacotherapy.

Innovative Vancomycin-Loaded Hydrogel-Based Systems - New Opportunities for the Antibiotic Therapy.

Purpose: Surgical site infections pose a significant challenge for medical services. Systemic antibiotics may be insufficient in preventing bacterial biofilm development. With the local administration of antibiotics, it is easier to minimize possible complications, achieve drugs' higher concentration at the injured site, as well as provide their more sustained release. Therefore, the main objective of the proposed herein studies was the fabrication and characterization of innovative hydrogel-based composites for local vancomycin (VAN) therapy. Methods: Presented systems are composed of ionically gelled chitosan particles loaded with vancomycin, embedded into biomimetic collagen/chitosan/hyaluronic acid-based hydrogels crosslinked with genipin and freeze-dried to serve in a flake/disc-like form. VAN-loaded carriers were characterized for their size, stability, and encapsulation efficiency (EE) using dynamic light scattering technique, zeta potential measurements, and UV-Vis spectroscopy, respectively. The synthesized composites were tested in terms of their physicochemical and biological features. Results: Spherical structures with sizes of about 200 nm and encapsulation efficiencies reaching values of approximately 60% were obtained. It was found that the resulting particles exhibit stability over time. The antibacterial activity of the developed materials against Staphylococcus aureus was established. Moreover, in vitro cell culture study revealed that the surfaces of all prepared systems are biocompatible as they supported the proliferation and adhesion of the model MG-63 cells. In addition, we have demonstrated significantly prolonged VAN release while minimizing the initial burst effect for the composites compared to bare nanoparticles and verified their desired physicochemical features during swellability, and degradation experiments. Conclusion: It is expected that the developed herein system will enable direct delivery of the antibiotic at an exposed to infections surgical site, providing drugs sustained release and thus will reduce the risk of systemic toxicity. This strategy would both inhibit biofilm formation and accelerate the healing process.

Efficacy of Intrawound Vancomycin in Prevention of Periprosthetic Joint Infection After Primary Total Knee Arthroplasty: A Prospective Double-Blinded Randomized Control Trial.

BACKGROUND: Periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is a devastating complication. Intrawound vancomycin powder has been shown to reduce infection rates in spine surgery, but its role in arthroplasty remains controversial. This prospective randomized control trial aimed to evaluate the efficacy of intrawound vancomycin in preventing PJI after primary TKA. METHODS: A total of 1,022 patients were randomized to the study group (n = 507, who received 2 grams intrawound vancomycin powder before arthrotomy closure) or to the control group (n = 515, no local vancomycin) with a minimum follow-up of 12-months. The primary outcome was the incidence of PJI or surgical site infection (SSI). Secondary outcomes included associated minor complications such as stitch abscess, persistent wound drainage, and delayed stitch removal. Other parameters evaluated include reoperation rates and incidences of nephrotoxicity. RESULTS: The overall infection rate in 1,022 patients was 0.66%. There was no significant difference in PJI rate in the study group (N = 1; 0.2%) versus the control group (N = 3; 0.58%), P = .264. Reoperation rates in the study group (N = 4; 0.78%) and control (N = 5; 0.97%), and SSI rates in the study (N = 1; 0.2%) and control groups (N = 2; 0.38%) were comparable. The Vancomycin cohort, however, demonstrated a significantly higher number of minor wound complications (n = 67; 13.2%) compared to the control group (n = 39; 7.56%, P < .05). Subgroup analysis showed diabetics in the study group to also have a higher incidence of minor wound complications (24 [14.1%] versus 10 [6.2%]; P < 05]. Multivariate analyses found that vancomycin use (odds ratio = 1.64) and smoking (odds ratio = 1.85) were associated with an increased risk of developing minor wound complications. No cases of nephrotoxicity were reported. CONCLUSIONS: Intrawound vancomycin powder does not appear to reduce PJI/SSI rate in primary total knee arthroplasties, including high-risk groups. Although safe from a renal perspective, intrawound vancomycin was associated with an increase in postoperative aseptic wound complications. Intrawound vancomycin may not be effective in reducing the rate of PJI in primary TKA.

An injectable, chitosan-based hydrogel prepared by Schiff base reaction for anti-bacterial and sustained release applications.

Injectable hydrogels, providing sustained release as implanted materials, have received tremendous attention. In this study, chitosan-based hydrogels were prepared via Schiff base reaction of the aldehyde groups on Poly(NIPAM-co-FBEMA) and the amine groups on chitosan. Owing to the dynamic covalent linkage, the SC/PNF hydrogels exhibit pH-responsive, reversible sol-gel transition, injectable, and self-healing capacity. The mechanical strength of SC/PNF hydrogels can be operated simply by switching the composition or solid content of Poly(NIPAM-co-FBEMA) copolymers. Rheological analyses, including frequency sweeps, strain sweep scanning, and dynamic time sweeps, were employed to demonstrate the relationship between storage modulus (G'), loss modulus (G″), and composition of the SC/PNF hydrogels. In vitro release behaviors reveal that vancomycin-loaded SC/PNF hydrogel could contribute to both the initial burst release (over 1000 ppm within 4 h) and the sustained release (3000 ppm for at least 30 days). Pristine SC/PNF hydrogel holds good biocompatibility toward L929 cells and S. aureus that it degrades as incubated with S. aureus. However, vancomycin-wrapped SC/PNF hydrogel possesses a rapid bacterial-killing effect with a clear inhibition zone. In short, the SC/PNF hydrogels deliver not only sustainable release ability but also tunable physical properties, which are expected to be an outstanding candidate for non-invasive, anti-infection applications.

Cascade-Targeted Nanoplatforms for Synergetic Antibiotic/ROS/NO/Immunotherapy against Intracellular Bacterial Infection.

Intracellular bacteria in dormant states can escape the immune response and tolerate high-dose antibiotic treatment, leading to severe infections. To overcome this challenge, cascade-targeted nanoplatforms that can target macrophages and intracellular bacteria, exhibiting synergetic antibiotic/reactive oxygen species (ROS)/nitric oxide (NO)/immunotherapy, were developed. These nanoplatforms were fabricated by encapsulating trehalose (Tr) and vancomycin (Van) into phosphatidylserine (PS)-coated poly[(4-allylcarbamoylphenylboric acid)-ran-(arginine-methacrylamide)-ran-(N,N'-bisacryloylcystamine)] nanoparticles (PABS), denoted as PTVP. PS on PTVP simulates a signal of "eat me" to macrophages to promote cell uptake (the first-step targeting). After the uptake, the nanoplatform in the acidic phagolysosomes could release Tr, and the exposed phenylboronic acid on the nanoplatform could target bacteria (the second-step targeting). Nanoplatforms can release Van in response to infected intracellular overexpressed glutathione (GSH) and weak acid microenvironment. l-arginine (Arg) on the nanoplatforms could be catalyzed by upregulated inducible nitric oxide synthase (iNOS) in the infected macrophages to generate nitric oxide (NO). N,N'-Bisacryloylcystamine (BAC) on nanoplatforms could deplete GSH, allow the generation of ROS in macrophages, and then upregulate proinflammatory activity, leading to the reinforced antibacterial capacity. This nanoplatform possesses macrophage and bacteria-targeting antibiotic delivery, intracellular ROS, and NO generation, and pro-inflammatory activities (immunotherapy) provides a new strategy for eradicating intracellular bacterial infections.

Antibiotic calcium sulphate beads lower the bacterial burden and prevent infection in a mouse model of periprosthetic joint infection.

Aims: Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods: A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results: The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log10 (95%) and 1.5-log10 (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 103 vs 7.0 × 104; p = 0.022; 3.6 × 103 vs 1.0 × 105; p = 0.007, respectively) at POD 21. There was a significant 1.6-log10 (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 100 vs 4.7 × 101, respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion: In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections.

Cellular uptake and in vitro antibacterial activity of lipid-based nanoantibiotics are influenced by protein corona.

Bacteria have evolved survival mechanisms that enable them to live within host cells, triggering persistent intracellular infections that present significant clinical challenges due to the inability for conventional antibiotics to permeate cell membranes. In recent years, antibiotic nanocarriers or 'nanoantibiotics' have presented a promising strategy for overcoming intracellular infections by facilitating cellular uptake of antibiotics, thus improving targeting to the bacteria. However, prior to reaching host cells, nanocarriers experience interactions with proteins that form a corona and alter their physiological response. The influence of this protein corona on the cellular uptake, drug release and efficacy of nanoantibiotics for intracellular infections is poorly understood and commonly overlooked in preclinical studies. In this study, protein corona influence on cellular uptake was investigated for two nanoparticles; liposomes and cubosomes in macrophage and epithelial cells that are commonly infected with pathogens. Studies were conducted in presence of fetal bovine serum (FBS) to form a biologically relevant protein corona in an in vitro setting. Protein corona impact on cellular uptake was shown to be nanoparticle-dependent, where reduced internalization was observed for liposomes, the opposite was observed for cubosomes. Subsequently, vancomycin-loaded cubosomes were explored for their drug delivery performance against intracellular small colony variants of Staphylococcus aureus. We demonstrated improved bacterial killing in macrophages, with greater reduction in bacterial viability upon internalization of cubosomes mediated by the protein corona. However, no differences in efficacy were observed in epithelial cells. Thus, this study provides insights and evidence to the role of protein corona in modulating the performance of nanoparticles in a dynamic manner; these findings will facilitate improved understanding and translation of future investigations from in vitro to in vivo.

Is shorter also better in the treatment of Clostridioides difficile infection?

OBJECTIVES: To assess the effectiveness of shortened regimens of vancomycin or fidaxomicin in the treatment of Clostridioides difficile infection (CDI). METHODS: Adult patients with CDI hospitalized from January 2022 to May 2023 were included in this observational study. In patients with CDI treated with vancomycin or fidaxomicin, antibiotic treatment was discontinued after either 5 or 7 days of vancomycin or 5 days of fidaxomicin if there was a clinical response and improvement in laboratory parameters. The control cohort was treated with the standard 10 day regimen of either vancomycin or fidaxomicin. The follow-up was 60 days. Causative C. difficile strains were characterized by ribotyping and toxin gene detection when available. RESULTS: Twenty-five patients (median age 76 years) received shortened treatment with vancomycin (n = 21), or fidaxomicin (n = 4). Five cases fulfilled the criteria for severe CDI. Twenty-three patients completed follow-up; two died from causes other than CDI, and two developed recurrent CDI (8.0%). Ribotypes (RTs) 001 and 014 were the most prevalent with 20% each. In two C. difficile isolates, binary toxin genes were detected (RTs 078 and 023). In the control group of 22 patients recurrent CDI developed in 5 patients (22.7%). No statistically significant differences were found between the groups. CONCLUSIONS: Shortened treatment regimens for CDI with vancomycin and fidaxomicin were shown to be effective in our cohort of patients compared with 10 days of treatment. The recurrence rate was lower in the study group. A larger, prospective, double-blind, randomized, multicentre study is needed to support our findings.

The Impact of Antibiotic Strategy on Outcomes in Surgically Managed Necrotizing Enterocolitis.

BACKGROUND: We sought to evaluate postoperative antibiotic practices in a large population of patients with necrotizing enterocolitis (NEC) and determine whether any regimens were associated with better outcomes. METHODS: The Pediatric Health Information Systems (PHIS) database was queried to identify patients who underwent an intestinal resection for acute NEC between July, 2016 and June, 2021. Data regarding post-resection antibiotic therapy, cutaneous or intraabdominal infection, and fungal or antibiotic-resistant infection were collected. RESULTS: 130 infants at 38 children's hospitals met inclusion criteria. Postoperative antibiotics were administered for a median of 13 days. The most frequently used antibiotics were vancomycin and piperacillin/tazobactam. Antibiotic duration greater than five days was not associated with a lower incidence of infection. No antibiotic was associated with a lower incidence of any of the complications assessed, although ampicillin was associated with more infections, overall. The incidence of fungal infection and treatment with a parenteral anti-fungal medication was greater with vancomycin. No antibiotic combination was used enough to be assessed. CONCLUSIONS: Administration of antibiotics for more than five days after resection for NEC was not associated with better infectious outcomes and no single antibiotic demonstrated superior efficacy. Consistent with prior studies, fungal infections were more frequent with vancomycin. TYPE OF STUDY: Retrospective database study, level 3B. LEVEL OF EVIDENCE: II.

Effects of lung inflammation and injury on pulmonary tissue penetration of meropenem and vancomycin in a model of unilateral lung injury.

OBJECTIVE: The timing and dosing of antimicrobial therapy are key in the treatment of pneumonia in critically ill patients. It is uncertain whether the presence of lung inflammation and injury affects tissue penetration of intravenously administered antimicrobial drugs. The effects of lung inflammation and injury on tissue penetration of two antimicrobial drugs commonly used for pneumonia were determined in an established model of unilateral lung injury. METHODS: Unilateral lung injury was induced in the left lung of 13 healthy pigs through cyclic rinsing; the right healthy lung served as control. Infusions of meropenem and vancomycin were administered and concentrations of these drugs in lung tissue, blood, and epithelial lining fluid (ELF) were compared over a period of 6 h. RESULTS: Median vancomycin lung tissue concentrations and penetration ratio were higher in inflamed and injured lungs compared with uninflamed and uninjured lungs (AUC0-6h: P = 0.003 and AUCdialysate/AUCplasma ratio: P = 0.003), resulting in higher AUC0-24/MIC. Median meropenem lung tissue concentrations and penetration ratio in inflamed and injured lungs did not differ from that in uninflamed and uninjured lungs (AUC0-6: P = 0.094 and AUCdialysate/AUCplasma ratio: P = 0.173). The penetration ratio for both vancomycin and meropenem into ELF was similar in injured and uninjured lungs. CONCLUSION: Vancomycin penetration into lung tissue is enhanced by acute inflammation and injury, a phenomenon barely evident with meropenem. Therefore, inflammation in lung tissue influences the penetration into interstitial lung tissue, depending on the chosen antimicrobial drug. Measurement of ELF levels alone might not identify the impact of inflammation and injury.

[Clinical efficacy of intraarticular vancomycin in preventing early periprosthetic joint infection after primary knee arthroplasty].

Objective: To investigate the clinical effect of intraarticular vancomycin on early periprosthetic joint infection (PJI) in knee arthroplasty and the incidence of postoperative complications. Methods: This is a retrospective cohort study. The clinical data of 1 867 patients who underwent primary knee arthroplasty at Department of Joint Surgery, the Affiliated Hospital of Qingdao University from April 2022 to June 2023 were retrospectively analysed, including total knee arthroplasty (TKA), robotic-assisted total knee arthroplasty (RA-TKA) and unicondylar knee arthroplasty (UKA). There were 687 males and 1 180 females, aged (68.0±11.2)years(range:45 to 87 years). Patients were divided into the vancomycin group and the control group according to whether or not intra-articular injection of 1 g of vancomycin powder dissolved in 30 ml of saline was performed after intraoperative joint capsule closure. In the vancomycin group, 925 patients were included, including 782 TKA, 27 RA-TKA and 116 UKA.In the control group, 942 patients were included, including 767 TKA, 99 RA-TKA and 76 UKA. Early PJI, wound complications, and vancomycin-related toxicity including acute renal collapse, ototoxicity, and allergic reactions were assessed within 3 months postoperatively. The data were compared using the independent sample t test, χ² test, and Fisher's exact probability method, as appropriate. Major Extremity Trauma Research Consortium (METRC). Results: No PJI was found in all patients in the vancomycin group.Five cases (0.7%,5/767) of early PJI were found in TKA patients in the control group, with a statistically significant difference (P=0.030); 1 case of early PJI was found in each RA-TKA and UKA patients, with non-significant difference compared with vancomycin group (all P>0.05). Two cases (0.3%,2/782) of incisional complications were found in TKA patients in the vancomycin group, and 4 cases (0.5%, 4/767) of incisional complications were found in TKA patients in the control group, with non-significant difference(P=0.449); no incisional complication was found in RA-TKA patients in the vancomycin group, and 1 case (1.0%,1/99) of incisional complications were found in RA-TKA patients in the control group, the difference was not statistically significant (P>0.05); no incisional complication was found in both groups of UKA patients.No vancomycin-related acute kidney injury, ototoxicity, or allergic reactions was observed in all patients. Conclusion: Intra-articular injection of 1 g of vancomycin suspension after arthrotomy closure during TKA maybe lower the risk of early PJI without increasing the risk of wound complication and vancomycin-associated systemic toxicity.