A case report of Vancomycin in the treatment of Q fever endocarditis.

The patient, a 43-year-old male, was admitted to the hospital with gradually aggravated exertional palpitations and chest tightness over a 2-day period. Upon hospital admission, a cardiac ultrasound revealed aortic valve redundancy, however multiple blood culture investigations came back negative. Blood mNGS was perfected, revealing Coxiella burnetii, and the diagnosis of Q fever (query fever) was established. The temperature and inflammatory indices of the patient were all normal with the treatment of vancomycin before cardiac surgery. But for the potential liver damage of and the Coxiella burnetii was still positive in the anti-phase II IgG titer, the doxycycline and hydroxychloroquine instead of vancomycin were applied for the patient. Despite receiving standardized anti-infective therapy of doxycycline combined with hydroxychloroquine, this patient had fever and increased leukocytes following surgery. After the addition of vancomycin as an anti-infective treatment, the temperature and leukocytes improved quickly. During the treatment of vancomycin, a discovery of liver injury may have resulted. These findings provide new therapy options for future professionals.

Effective treatment of Clostridioides difficile infection improves survival and affects graft-versus-host disease: a multicenter study by the Polish Adult Leukemia Group.

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.

A Case Report of Corynebacterium Tuberculostearicum Infection.

BACKGROUND: The goal was to report a rare case of lymphadenitis caused by Corynebacterium tuberculostearicum, and the laboratory's coping approach in the isolation and identification of this rare pathogen to improve the understanding of the disease. METHODS: Lymph node biopsy was performed in a patient with suspected tuberculous lymphadenitis, and the biopsy tissue was isolated and cultured. RESULTS: The culture was Gram positive Corynebacterium, which was identified as Corynebacterium tuberculostearicum by microbial mass spectrometry and 16S rRNA gene sequencing. Antimicrobial susceptibility test showed that the drug was sensitive to daptomycin, doxycycline, gentamicin, linezolid, vancomycin, and meropenem, but resistant to ciprofloxacin, clindamycin, erythromycin, rifampicin, compound sulfamethoxazole, ceftriaxone, and cefepime. CONCLUSIONS: This is a case of Corynebacterium tuberculostearicum infection. Case reports of Corynebacterium tuberculostearicum infection are relatively rare in China. Through case study, we can provide help for laboratory isolation, identification, clinical diagnosis, and treatment.

Longitudinal antimicrobial susceptibility trends of canine Staphylococcus pseudintermedius.

Antimicrobial resistance within Staphylococcus pseudintermedius poses a significant risk for the treatment of canine pyoderma and as a reservoir for resistance and potential zoonoses, but few studies examine long-term temporal trends of resistance. This study assesses the antimicrobial resistance prevalence and minimum inhibitory concentration (MIC) trends in S. pseudintermedius (n=1804) isolated from canine skin samples at the Cornell University Animal Health Diagnostic Center (AHDC) between 2007 and 2020. Not susceptible (NS) prevalence, Cochran-Armitage tests, logrank tests, MIC50 and MIC90 quantiles, and survival analysis models were used to evaluate resistance prevalence and temporal trends to 23 antimicrobials. We use splines as predictors in accelerated failure time (AFT) models to model non-linear temporal trends in MICs. Multidrug resistance was common among isolates (47%), and isolates had moderate to high NS prevalence to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, the macrolides/lincosamides, the tetracyclines, and trimethoprim-sulfamethoxazole. However, low levels of NS to amikacin, rifampin, and vancomycin were observed. Around one third of isolates (38%) were found to be methicillin resistant S. pseudintermedius (MRSP), and these isolates had a higher prevalence of NS to all tested antimicrobials than methicillin susceptible isolates. Amongst the MRSP isolates, one phenotypically vancomycin resistant isolate (MIC >16 µg/mL) was identified, but genomic sequence data was unavailable. AFT models showed increasing MICs across time to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, and the macrolides/lincosamides, and decreasing temporal resistance (decreasing MICs) to doxycycline was observed amongst isolates. Notably, ATF modeling showed changes in MIC distributions that were not identified using Cochran-Armitage tests on prevalence, MIC quantiles, and logrank tests. Increasing resistance amongst these S. pseudintermedius isolates highlights the need for rational, empirical prescribing practices and increased antimicrobial resistance (AMR) surveillance to maintain the efficacy of current therapeutic agents. AFT models with non-linear predictors may be a useful, breakpoint-independent, surveillance tool alongside other modeling methods and antibiograms.

Effectiveness of vancomycin powder for preventing postoperative spinal infection.

OBJECTIVE: This study aimed to assess the effectiveness of Vancomycin Power (VP) and the occurrence of resistant organisms after four-year of routine VP use. METHODS: The study included 1063 patients who underwent posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) between January 2010 and February 2020. Intrawound VP was applied to all instrumented fusions starting in January 2016. The patients were divided into two groups: those who did not apply VP (non-VP) (n = 605) between 2010 and 2015, and those who did apply VP (VP) (n = 458) between 2016 and 2020. The baseline characteristics, clinical symptoms, infection rate, and causative organisms were compared between the two groups. RESULTS: The rate of PSI was not significantly different between the non-VP group (1.32 %, n = 8) and the VP group (1.09 %, n = 5). Although adjusted by diabetes mellitus, VP still did not show statistical significance (OR = 0.757 (0.245-2.345), p = 0.630). There were no critical complications that were supposed to relation with vancomycin powder. In the 13 cases of PSI, seven pathogens were isolated, with a gram-negative organism identified in the non-VP group. However, the type of organism was not significantly different between the two groups. CONCLUSIONS: The use of intrawound VP may not affect the PSI and occurrence of resistant organism and may not cause critical complications. Therefore, clinicians may decide whether to use VP for preventing PSI not worrying about its safety.

Leonurine alleviates vancomycin nephrotoxicity via activating PPARγ and inhibiting the TLR4/NF-κB/TNF-α pathway.

Vancomycin (VCM) is the first-line antibiotic for severe infections, but nephrotoxicity limits its use. Leonurine (Leo) has shown protective effects against kidney damage. However, the effect and mechanism of Leo on VCM nephrotoxicity remain unclear. In this study, mice and HK-2 cells exposed to VCM were treated with Leo. Biochemical and pathological analysis and fluorescence probe methods were performed to examine the role of Leo in VCM nephrotoxicity. Immunohistochemistry, q-PCR, western blot, FACS, and Autodock software were used to verify the mechanism. The present results indicate that Leo significantly alleviates VCM-induced renal injury, morphological damage, and oxidative stress. Increased intracellular and mitochondrial ROS in HK-2 cells and decreased mitochondrial numbers in mouse renal tubular epithelial cells were reversed in Leo-administrated groups. In addition, molecular docking analysis using Autodock software revealed that Leo binds to the PPARγ protein with high affinity. Mechanistic exploration indicated that Leo inhibited VCM nephrotoxicity via activating PPARγ and inhibiting the TLR4/NF-κB/TNF-α inflammation pathway. Taken together, our results indicate that the PPARγ inhibition and inflammation reactions were implicated in the VCM nephrotoxicity and provide a promising therapeutic strategy for renal injury.

Removal of common antimicrobial agents by sustained low-efficiency dialysis.

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin-tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for 8 hours during SLED (on-SLED). Arterial samples were collected every 2 hours for up to 6 hours while not receiving SLED (off-SLED) for the calculation of SLED clearance, half-life (t1/2) on-SLED and off-SLED, and the fraction of removal by SLED (fD). Twenty-one patients completed the study: 52% male, mean age (±SD) 53 ± 13 years, and mean weight of 98 ± 30 kg. Eighty-six percent had AKI, and 4 patients were receiving cefepime, 3 daptomycin, 10 meropenem, 6 piperacillin-tazobactam, and 13 vancomycin. The average SLED time was 7.3 ± 1.1 hours, and the mean ultrafiltration rate was 95 ± 52 mL/hour (range 10-211). The t1/2 on-SLED was substantially lower than the off-SLED t1/2 for all antimicrobials, and the SLED fD varied between 44% and 77%. An 8-hour SLED session led to significant elimination of most antimicrobials evaluated. If SLED is performed, modification of the dosing regimen is warranted to avoid subtherapeutic concentrations.

Garlic-Derived Exosome-like Nanovesicles-Based Wound Dressing for Staphylococcus aureus Infection Visualization and Treatment.

Garlic-derived exosome-like nanovesicles (GELNs) could function in interspecies communication and may serve as natural therapeutics to regulate the inflammatory response or as nanocarriers to efficiently deliver specific drugs. Staphylococcus aureus (S. aureus) is able to hide within host cells to evade immune clearance and antibiotics, leading to life-threatening infections. On-site detection and efficient treatment of intracellular S. aureus infection in wounds remain challenging. Herein, we report a thermosensitive, injectable, visible GELNs-based wound dressing, Van@GELNs/F127 hydrogel (gel Van@GELNs), which is H2O2-responsive and can slowly release vancomycin into host cells forS. aureus infection visualization and treatment in wounds. GELNs show inherent antibacterial activity, which is significantly enhanced after loading vancomycin. Both GELNs and Van@GELNs have the ability to be internalized by cells, so Van@GELNs are more effective than free vancomycin in killing S. aureus in RAW 264.7 macrophages. When applied to an S. aureus-infected wound on a mouse, the colorless HRP&ABTS/Van@GELNs/F127 solution immediately changes to a green hydrogel and shows better therapeutic effect than vancomycin. Thus, direct visualization by the naked eye and effective treatment of S. aureus infection in wounds are achieved by gel Van@GELNs. We anticipate gel Van@GELNs be applied for the theranostics of S. aureus infection diseases in the clinic in the near future.

Cerebrospinal fluid drain infection caused by pandrug-resistant Staphylococcus epidermidis successfully treated with ceftaroline in combination with fosfomycin and vancomycin.

External ventricular drain-related cerebrospinal fluid infection represents a fearsome complication of neurosurgical interventions. Although vancomycin represents the standard of care for methicillin-resistant CoNS healthcare-associated ventriculitis, resistance phenomena have been described. We reported a case of a persistent external ventricular fluid drain infection after device removal by pandrug-resistant Staphylococcus epidermidis successfully treated with intravenous ceftaroline in combination with fosfomycin and vancomycin. No evidence regarding pandrug-resistant S. epidermidis therapy currently exists to our knowledge. In this case, the S. epidermidis phenotype emerged during the therapy course, possibly due to initial device retention, biofilm formation and the host immune impaired response. Despite being poorly studied in vivo, ceftaroline may be considered an option when other alternatives are unavailable, thanks to its described activity against CoNS in vitro. This case extends the experience with ceftaroline for central nervous system infections suggesting it could also be used in high antimicrobial resistance settings for immunocompromised people.

Intraperitoneal vancomycin plus levofloxacin for the treatment of peritoneal dialysis-related peritonitis in patients with no response to cefazolin plus ceftazidime.

INTRODUCTION: Peritoneal dialysis-related peritonitis (PDRP) should be treated as soon as possible by an empirical regimen without waiting for effluent bacterial culture results. We retrospectively investigated patients treated with vancomycin plus levofloxacin as a treatment regimen if there was no response to cefazolin plus ceftazidime. MATERIALS AND METHODS: We collected records of adult patients with PDRP from January 1, 2013, to November 30, 2020. The characteristics of episodes of PDRP with no response to cefazolin plus ceftazidime treated by intraperitoneal (IP) injection of vancomycin plus levofloxacin were analyzed. RESULTS: 118 episodes of PDRP were recorded, among which 115 episodes were treated with IP antibiotics. 93 episodes were treated with cefazolin plus ceftazidime. In 38 episodes, treatment was switched to IP injection of vancomycin plus levofloxacin if there was no response to cefazolin plus ceftazidime. 26/38 (68.4%) episodes were cured by vancomycin plus levofloxacin. Fever, diabetes, fasting glucose, a decrease in effluent leukocytes on day 3 and day 5, and Charlson Comorbidity Index (CCI) scores were significantly different between uncured and cured episodes. No variable was associated with treatment failure after multiple logistic regression. Fever, diabetes, a decrease in effluent leukocytes on day 3, and CCI score were associated with treatment failure after univariable logistic regression. CONCLUSION: Vancomycin plus levofloxacin may be effective if patients are not responsive to cefazolin plus ceftazidime.

Rhodococcus infection: a 10-year retrospective analysis of clinical experience and antimicrobial susceptibility profile.

Rhodococcus equi is an opportunistic pathogen known to cause pulmonary and extrapulmonary disease among immunocompromised patients. Treatment is frequently challenging due to intrinsic resistance to multiple antibiotic classes. While non-equi Rhodococcus spp. are prevalent, their clinical significance is poorly defined. There is also limited data on antibiotic susceptibility testing (AST) of Rhodococcus infection in humans. We conducted a single-center, retrospective cohort study evaluating clinical characteristics, microbiologic profile, and AST of Rhodococcus infections between June 2012 and 2022 at our tertiary academic medical center. Identification of Rhodococcus spp. was performed by Sanger 16S rRNA gene sequencing and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry, and AST was performed by agar dilution. Three hundred twenty-two isolates of Rhodococcus spp. were identified from blood (50%), pulmonary (26%), and bone/joint (12%) sources. R. equi/hoagii, R. corynebacterioides, and R. erythropolis were the most frequently isolated species, with 19% of isolates identified only to genus level. One hundred ninety-nine isolates evaluated for AST demonstrated high-level resistance to amoxicillin/clavulanate, cephalosporins, and aminoglycosides. More than 95% susceptibility to imipenem, vancomycin, linezolid, rifampin, and clarithromycin was observed. Non-equi species showed a significantly more favorable AST profile relative to R. equi. Clinically significant Rhodococcus infection was rare with 10 cases diagnosed (majority due to R. equi) and managed. The majority of patients received 2- or 3-drug combination therapy for 2-6 months, with favorable clinical response. Significant differences in AST were observed between R. equi and non-equi species. Despite high antimicrobial resistance to several antibiotic classes, imipenem and vancomycin remain appropriate empiric treatment options for R. equi. Future research evaluating mechanisms underlying antimicrobial resistance is warranted.

Effect of Antibiotic Spacer Dosing on Treatment Success in Two-Stage Exchange for Periprosthetic Joint Infection.

INTRODUCTION: In two-stage exchange for periprosthetic joint infection (PJI), adding antibiotics to cement spacers is the standard of care; however, little is known about optimal dosage. There is emphasis on using >3.6 g of total antibiotic, including ≥2.0 g of vancomycin, per 40 g of cement, but these recommendations lack clinical evidence. We examined whether recommended antibiotic spacer doses affect treatment success. METHODS: This was a retrospective review of 202 patients who underwent two-stage exchange for PJI from 2004 to 2020 with at least 1-year follow-up. Patients were separated into high (>3.6 g of total antibiotic per 40 g of cement) and low-dose spacer groups. Primary outcomes were overall and infectious failure. RESULTS: High-dose spacers were used in 80% (162/202) of patients. High-dose spacers had a reduced risk of overall (OR, 0.37; P = 0.024) and infectious (OR, 0.35; P = 0.020) failure for infected primary arthroplasties, but not revisions. In multivariate analysis, vancomycin dose ≥2.0 g decreased the risk of infectious failure (OR, 0.31; P = 0.016), although not overall failure (OR, 0.51; P = 0.147). CONCLUSION: During two-stage exchange for PJI, spacers with greater than 3.6 g of total antibiotic may reduce overall and infectious failure for infected primary arthroplasties. Furthermore, using at least 2.0 g of vancomycin could independently decrease the risk of infectious failure.

Antibacterial activity of ibezapolstat against antimicrobial-resistant clinical strains of Clostridioides difficile.

Antimicrobial resistance is emerging in clinical strains of Clostridioides difficile. Ibezapolstat (IBZ) is a DNA polymerase IIIC inhibitor that has completed phase II clinical trials. IBZ has potent in vitro activity against wild-type, susceptible strains but its effect on C. difficile strains with reduced susceptibility to metronidazole (MTZ), vancomycin (VAN), or fidaxomicin (FDX) has not been tested. The primary objective of this study was to test the antibacterial properties of IBZ against multidrug-resistant C. difficile strains. The in vitro activity, bactericidal, and time-kill activity of IBZ versus comparators were evaluated against 100 clinical strains of which 59 had reduced susceptibility to other C. difficile antibiotics. Morphologic changes against a multidrug resistance strain were visualized by light and scanning electron microscopy. The overall IBZ MIC50/90 values (µg/mL) for evaluated C. difficile strains were 4/8, compared with 2/4 for VAN, 0.5/1 for FDX, and 0.25/4 for MTZ. IBZ MIC50/90 values did not differ based on non-susceptibility to antibiotic class or number of classes to which strains were non-susceptible. IBZ bactericidal activity was similar to the minimum inhibitory concentration (MIC) and maintained in wild-type and non-susceptible strains. Time-kill assays against two laboratory wild-type and two clinical non-susceptible strains demonstrated sustained IBZ activity despite reduced killing by comparator antibiotics for IBZ and VAN non-susceptible strains. Microscopy visualized increased cell lengthening and cellular damage in multidrug-resistant strains exposed to IBZ sub-MIC concentrations. This study demonstrated the potent antibacterial activity of IBZ against a large collection of C. difficile strains including multidrug-resistant strains. This study highlights the therapeutic potential of IBZ against multidrug-resistant strains of C. difficile.

Efficacy of prophylactic use of intraoperative vancomycin powder in preventing surgical site infection in neurological surgeries in Irrua, Nigeria: A randomized controlled study.

PURPOSE: The objective was to determine the efficacy of intraoperative vancomycin powder in preventing SSIs in neurological surgeries. METHODS: A prospective randomized controlled study of patients who had clean cranial and non-implant spine surgeries at the Irrua Specialist Teaching Hospital, Irrua, Nigeria from February 1, 2021 to January 31, 2022. Patients were randomized into two groups. Group A patients had prophylactic intraoperative vancomycin powder applied to the surgical bed before wound closure while group B patients did not. Patients in both groups were followed up for 30 days post-operatively for evidence of SSI. The occurrence of SSIs was determined using clinical and laboratory parameters. Baseline characteristics, operative details, rates of wound infection, and microbiological data for each case were recorded. Data was analyzed using Statistical Package for Scientific Solution (SPSS) version 23 software. RESULTS: Forty-two patients were randomized into 2 groups of 21 patients each. The age range of the patients was 20 to 80 years. The majority of the patients were males (32 out of 42). The mean age of patients in group A was 48.05 ± 17.03 years, while group B had a mean age of 45.95 ± 19.14 years. The mean Body Mass Index of patients in groups A and B were 23.92 ± 5.21 and 23.21 ± 3.99 respectively. Seven out of 21 patients (33.3 %) in the control group ( group B) had superficial SSIs while no patient in the experimental group had SSI, p-value < 0.05. The organisms cultured were Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. CONCLUSION: Intraoperative vancomycin powder was effective in reducing the rate of SSIs following neurological surgeries and without adverse drug reactions.

Primary clostridium difficile infection in patients with ulcerative colitis: Case report and literature review.

RATIONALE: Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated disorder characterized by inflammation of the gastrointestinal tract. Patients with IBD are susceptible to various complications, including the coexistence of Clostridioides difficile infection (CDI). The incidence of IBD combined with difficile infection is higher in patients with compromised immune function, which can lead to increased mortality. PATIENT CONCERNS: A 43-year-old male presented with recurrent episodes of mucus and bloody stools persisting for more than a month without any identifiable triggering factors. Initially, the stool consistency was normal, but it progressively shifted to a loose and watery texture, with up to 8 occurrences daily. DIAGNOSES: This case underscores the diagnosis of severe UC through colonoscopy and colonic biopsy, along with the supplementary identification of a positive result for Clostridioides difficile in the fecal sample. INTERVENTIONS: The patient initiated infliximab therapy alongside a full vancomycin course, demonstrating the potential effectiveness of this intervention in managing early-stage ulcerative colitis with concurrent Clostridioides difficile infection. OUTCOMES: Following the completion of a full vancomycin course, the patient initiated infliximab therapy. The patient was free from significant discomfort, exhibited no fever, and had no mucopurulent bloody stools. A follow-up blood test indicated reduced inflammatory markers compared to the preoperative period, and the stools were normal. LESSONS: We illustrate the potential effectiveness of this medication by presenting an in-depth case report of a patient with early-stage UC. The report outlines the patient inclusion of infliximab to better manage UC inflammation alongside an adjunct vancomycin regimen, given the ineffectiveness of mesalazine therapy and the concurrent presence of Clostridium difficile infection. This case prompts consideration of therapeutic approaches for complex UC and contributes to advancing both research and clinical practice. Nonetheless, we should remain attentive to the variations and potential risks unique to each patient in order to formulate personalized treatment strategies.

Unravelling the complex interplay between antibiotic consumption and adaptive changes in methicillin-resistant Staphylococcus aureus.

OBJECTIVES: This study aims to elucidate the genomic dynamics driving the emergence of antimicrobial resistance (AMR), with a specific focus on the interplay between AMR and antimicrobial usage. METHODS: We conducted a comprehensive analysis using a ST239 methicillin-resistant Staphylococcus aureus (MRSA) dataset over a continuous 12-year period from a single hospital. Genomic analyses were performed tracking the changes in MRSA populations, particularly the emergence of reduced vancomycin susceptibility, and assessing the impact of glycopeptide use on these emergence events. RESULTS: Our findings reveal a significant correlation between hospital glycopeptide usage and the selection of MRSA strains with reduced vancomycin susceptibility. Genomic analyses provided insights into the molecular mechanisms driving resistance emergence, including the slowing of the molecular clock rate in response to heightened antimicrobial consumption. CONCLUSIONS: In conclusion, this study the highlights the complex dynamics between AMR and antimicrobial use at the hospital level. The observed correlation between antimicrobial consumption and the development of less susceptible MRSA strains underscores the importance of antimicrobial stewardship programmes and the establishment of optimal consumption thresholds for mitigating AMR effectively.

Developing an intervention package to optimise the management of vancomycin therapy using theory informed co-design.

BACKGROUND: Optimising the management of vancomycin by achieving target therapeutic concentrations early during therapy has been associated with reduced mortality and morbidity. Despite the availability of guidelines and training, the management of vancomycin remains suboptimal. OBJECTIVES: The primary outcome was the development of interventions and associated implementation strategies to optimise the management of vancomycin therapy. This paper describes how co-design process was used to build a theory informed intervention package, which was implemented across a wide range of in-patient hospital settings in Queensland, Australia. METHODS: This multiple methods study was conducted in four phases: 1) a baseline audit to identify the nature of the problem and associated determinants informed by stakeholder interviews 2) mapping these findings to the Theoretical Domains Framework (TDF) to identify behavioural correlates and modifiers 3) prioritising the behavioural modifiers and associated implementation strategies to inform a protype of the intervention in a series of co-design sessions and 4) implementing and evaluating the intervention package. The study was conducted across the four teaching hospitals in a large Queensland Hospital and Health Service across multiple healthcare disciplines namely nurses, doctors, and pharmacists. This intervention package was subsequently implemented across Queensland Health with the support of the local champions under the guidance of the steering group. RESULTS: Clinicians identified that a multifaceted intervention package and training which can be tailored to the health-care professional disciplines, would be best suited to shift clinician behaviour to align with guidelines. The findings from the co-design process aligned with theory-informed intervention package. Each of the intervention strategies varied in their frequency and popularity of use. CONCLUSIONS: The use of theory-informed and participatory approach assisted with the intervention development process and aligned the intervention content with the priorities of stakeholders. The TDF provided a structured process for developing intervention content which is both acceptable and useful to stakeholders and may improve the management of vancomycin.

The Effect of Vancomycin and Tobramycin Local Antibiotic Powder on Surgical Site Infections After Open Treatment of Fracture: A Retrospective Propensity-Matched Analysis.

OBJECTIVES: The aim of this study was to compare the effect of vancomycin/tobramycin local antibiotic powder (LAP) on surgical site infections (SSIs) after open treatment of fractures. DESIGN: This was a retrospective comparative study with propensity matching. SETTING: The study was set in an urban level 1 trauma center. PATIENTS SELECTION CRITERIA: Patients undergoing open procedures for fracture performed by a single surgeon before and after cessation of routine LAP use were included. OUTCOME MEASURES AND COMPARISONS: Deep and superficial SSIs were the measured outcomes. RESULTS: There were 652 open procedures for fracture performed by a single surgeon: LAP was used in 36.7% (114/310) of procedures before stopping its use, after which 342 procedures were performed without LAP. Comparison of all procedures performed with and without routine LAP use demonstrated no difference in infection rates, although there was a trend for the group without LAP to have fewer superficial SSIs (proportional difference [PD] -2.0%, 95% confidence interval [CI] -4.1% to 0.1%; P = 0.05) and more deep SSIs (PD 3.9%, 95% CI, -0.2% to 7.9%; P = 0.06). Prematch analysis demonstrated that LAP use was associated with external fixation (PD 8.5%, 95% CI, 1.6%-16.2%; P = 0.005), longer operative times (median difference 56.0 minutes, 95% CI, 39.0-74.0; P < 0.0001), greater estimated blood loss (median difference 70.0, 95% CI, 50.0-100.0; P < 0.0001), and no difference in superficial (PD 2.4%; 95% CI, -0.8% to 6.8%; P = 0.07) or deep SSIs (PD -1.6%, 95% CI, -6.2% to 4.1%; P = 0.54). After propensity matching (108 vs. 108) to control for the above differences, the LAP group, compared with the no LAP group, had no difference in superficial SSIs and was less likely to have deep SSIs (PD -8.3%, 95% CI, -16.2% to -0.2%; P = 0.04). CONCLUSIONS: The use of vancomycin and tobramycin LAP lowered the rate of deep SSIs after open treatment of fractures on propensity-matched analysis. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Injectable Nano-Micro Composites with Anti-bacterial and Osteogenic Capabilities for Minimally Invasive Treatment of Osteomyelitis.

The effective management of osteomyelitis remains extremely challenging due to the difficulty associated with treating bone defects, the high probability of recurrence, the requirement of secondary surgery or multiple surgeries, and the difficulty in eradicating infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Hence, smart biodegradable biomaterials that provide effective and precise local anti-infection effects and can promote the repair of bone defects are actively being developed. Here, a novel nano-micro composite is fabricated by combining calcium phosphate (CaP) nanosheets with drug-loaded GelMA microspheres via microfluidic technology. The microspheres are covalently linked with vancomycin (Van) through an oligonucleotide (oligo) linker using an EDC/NHS carboxyl activator. Accordingly, a smart nano-micro composite called "CaP@MS-Oligo-Van" is synthesized. The porous CaP@MS-Oligo-Van composites can target and capture bacteria. They can also release Van in response to the presence of bacterial micrococcal nuclease and Ca2+, exerting additional antibacterial effects and inhibiting the inflammatory response. Finally, the released CaP nanosheets can promote bone tissue repair. Overall, the findings show that a rapid, targeted drug release system based on CaP@MS-Oligo-Van can effectively target bone tissue infections. Hence, this agent holds potential in the clinical treatment of osteomyelitis caused by MRSA.