Antibiotic-eluting scaffolds with responsive dual-release kinetics facilitate bone healing and eliminate S. aureus infection.

Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.

Evaluation of Vancomycin Dose Needed to Achieve 24-Hour Area Under the Concentration-Time Curve to Minimum Inhibitory Concentration Ratio Greater Than or Equal to 400 Using Pharmacometric Approaches in Pediatric Intensive Care Patients.

OBJECTIVES: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400. DESIGN: Prospective population pharmacokinetic study of vancomycin. SETTING: Critically ill patients in quaternary care PICUs. PATIENTS: Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the ICUs at the University of Maryland Children's Hospital and Texas Children's Hospital were enrolled. INTERVENTIONS: Vancomycin was prescribed at doses and intervals chosen by the treating clinicians. MEASUREMENTS AND MAIN RESULTS: A median of four serum levels of vancomycin per patient were collected along with other variables for up to 7 days following the first administration. These data were used to characterize vancomycin pharmacokinetics and evaluate the factors affecting the variability in achieving AUC24/MIC ratio greater than or equal to 400 in PICU patients who are not on extracorporeal therapy. A total of 302 children with a median age of 6.0 years were enrolled. A two-compartment model described the pharmacokinetics of vancomycin with the clearance of 2.76 L/hr for a typical patient weighing 20 kg. The glomerular filtration rate estimated using either the bedside Schwartz equation or the chronic kidney disease in children equation was the only statistically significant predictor of clearance among the variables evaluated, exhibiting equal predictive performance. The trough levels achieving AUC24/MIC = 400 were 5.6-10.0 µg/mL when MIC = 1 µg/mL. The target of AUC24/MIC greater than or equal to 400 was achieved in 60.4% and 36.5% with the typical dosing regimens of 15 mg/kg every 6 and 8 hours (q6h and q8h), respectively. CONCLUSIONS: The pharmacokinetics of vancomycin in critically ill children were dependent on the estimated glomerular filtration rate only. Trough concentrations accurately predict AUC24. Typical pediatric vancomycin dosing regimens of 15 mg/kg q6h and q8h will often lead to AUC24/MIC under 400.

A multicentric, randomized, controlled clinical trial to study the impact of bedside model-informed precision dosing of vancomycin in critically ill children-BENEFICIAL trial.

BACKGROUND: Vancomycin is a commonly prescribed antibiotic to treat serious Gram-positive infections in children. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. In most countries, steady-state plasma concentrations are used as a surrogate parameter for this target AUC/MIC, but this practice has some drawbacks. Hence, AUC-based dosing using model-informed precision dosing (MIPD) tools has been proposed for increasing the target attainment rate and reducing vancomycin-related nephrotoxicity. Solid scientific evidence for these claimed benefits is lacking in children. This randomized controlled trial aims to investigate the large-scale utility of MIPD dosing of vancomycin in critically ill children. METHODS: Participants from 14 neonatal intensive care, pediatric intensive care, and pediatric hemo-oncology ward units from 7 hospitals are randomly allocated to the intervention or standard-of-care comparator group. In the intervention group, a MIPD dosing calculator is used for AUC-based dosing, in combination with extra sampling for therapeutic drug monitoring in the first hours of treatment, as compared to standard-of-care. An AUC24h between 400 and 600 is targeted, assuming an MIC of 1 mg/L. Patients in the comparator group receive standard-of-care dosing and monitoring according to institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400-600 between 24 and 48 h after the start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury during vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400-600 between 48 and 72 h after the start of vancomycin treatment, time to clinical cure, ward unit length-of-stay, hospital length-of-stay, and 30-day all-cause mortality. DISCUSSION: This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children. TRIAL REGISTRATION: Eudract number: 2019-004538-40. Registered on 2020-09-08 ClinicalTrials.gov NCT046666948. Registered on 2020-11-28.

A Case of Streptococcus iniae Pyocephalus, Subdural Empyema, and Diffuse Leptomeningitis in an Elderly Male: A Case Report.

We present a case of Streptococcus iniae causing leptomeningitis, pyocephalus, and subdural empyema in an elderly male from India. There have been only a handful of cases of S. iniae infection reported worldwide, and none of them have been from India. In this case, an elderly diabetic patient presenting with backache, headache, and fever with severe neurological worsening was diagnosed with severe invasive S. iniae infection. He had hydrocephalus that needed ventriculoperitoneal shunting. The patient was treated with a prolonged course of intravenous ampicillin and vancomycin.

Effect of low vs. high vancomycin trough level on the clinical outcomes of adult patients with sepsis or gram-positive bacterial infections: a systematic review and meta-analysis.

BACKGROUND & OBJECTIVE: The Infectious Disease Society of America guidelines recommend vancomycin trough levels of 15-20 mg/L for severe methicillin-resistant Staphylococcus aureus. However, recent consensus guidelines of four infectious disease organizations no longer recommend vancomycin dosing using minimum serum trough concentrations. Therefore, this study aimed to evaluate the impact of low (< 15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough levels on clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. METHOD: A systematic literature review from inception to December 2022 was conducted using four online databases, followed by a meta-analysis. The outcomes of interest included clinical response/efficacy, microbial clearance, length of ICU stay, treatment failure, nephrotoxicity, and mortality. RESULTS: Fourteen cohort studies met the inclusion criteria from which vancomycin trough concentration data were available for 5,228 participants. Our analysis found no association between vancomycin trough levels and clinical response [OR = 1.06 (95%CI 0.41-2.72], p = 0.91], microbial clearance [OR = 0.47 (95% CI 0.23-0.96), p = 0.04], ICU length of stay [MD=-1.01 (95%CI -5.73-3.71), p = 0.68], or nephrotoxicity [OR = 0.57 (95% CI 0.31-1.06), p = 0.07]. However, low trough levels were associated with a non-significant trend towards a lower risk of treatment failure [OR = 0.89 (95% CI 0.73-1.10), p = 0.28] and were significantly associated with reduced risk of all-cause mortality [OR = 0.74 (95% CI 0.62-0.90), p = 0.002]. CONCLUSION: Except for a lower risk of treatment failure and all-cause mortality at low vancomycin trough levels, this meta-analysis found no significant association between vancomycin trough levels and clinical outcomes in adult patients with sepsis or gram-positive bacterial infections.

An evaluation of the empirical vancomycin dosing guide in pediatric cardiology.

BACKGROUND: Higher doses of vancomycin are currently prescribed due to the emergence of bacterial tolerance and resistance. This study aimed to evaluate the efficacy and safety of the currently adopted vancomycin dosing guide in pediatric cardiology. METHODS: This was a single-center prospective cohort study with pediatric cardiac patients, younger than 14 years, from June 2020 to March 2021. The patients received intravenous vancomycin (40 mg/kg/day divided every 6-8 h) according to the department's vancomycin medication administration guide (MAG) for at least three days. RESULTS: In total, 88 cardiac patients were included, with a median age of 0.82 years (IQR: 0.25-2.9), and 51 (58%) received cardiopulmonary bypass surgery (CPB). The majority (71.6%, n = 61) achieved a serum vancomycin level within the therapeutic range (7-20 mg/L). Infants, young children, and children exposed to CPB surgery had an increased incidence of subtherapeutic vancomycin levels, [7 (29.2%); P = 0.033], [13 (54.2%); P = 0.01], and [21 (87.5%); P = 0.009] respectively. After the treatment, 8 (10%) patients had an elevated Serum creatinine (SCr) and 2 (2.5%) developed acute kidney injury (AKI). However, no significant difference was found between the patients developing AKI or an elevated SCr and the group who did not, in terms of clinical, therapeutic, and demographic characteristics, except for the decreased incidence of SCr elevation in patients receiving an ACE inhibitor, [4 (36.4%); P = 0.036]. CONCLUSION: Our institution followed MAG recommendations; however, subtherapeutic serum concentrations were evident in infants, young children, and CPB patients. Strategies to prevent AKI should be investigated, as the possible causes have not been identified in this study.

3D-printed porous titanium rods equipped with vancomycin-loaded hydrogels and polycaprolactone membranes for intelligent antibacterial drug release.

Implant-related infections pose significant challenges to orthopedic surgeries due to the high risk of severe complications. The widespread use of bioactive prostheses in joint replacements, featuring roughened surfaces and tight integration with the bone marrow cavity, has facilitated bacterial proliferation and complicated treatment. Developing antibacterial coatings for orthopedic implants has been a key research focus in recent years to address this critical issue. Researchers have designed coatings using various materials and antibacterial strategies. In this study, we fabricated 3D-printed porous titanium rods, incorporated vancomycin-loaded mPEG750-b-PCL2500 gel, and coated them with a PCL layer. We then evaluated the antibacterial efficacy through both in vitro and in vivo experiments. Our coating passively inhibits bacterial biofilm formation and actively controls antibiotic release in response to bacterial growth, providing a practical solution for proactive and sustained infection control. This study utilized 3D printing technology to produce porous titanium rod implants simulating bioactive joint prostheses. The porous structure of the titanium rods was used to load a thermoresponsive gel, mPEG750-b-PCL2500 (PEG: polyethylene glycol; PCL: polycaprolactone), serving as a novel drug delivery system carrying vancomycin for controlled antibiotic release. The assembly was then covered with a PCL membrane that inhibits bacterial biofilm formation early in infection and degrades when exposed to lipase solutions, mimicking enzymatic activity during bacterial infections. This setup provides infection-responsive protection and promotes drug release. We investigated the coating's controlled release, antibacterial capability, and biocompatibility through in vitro experiments. We established a Staphylococcus aureus infection model in rabbits, implanting titanium rods in the femoral medullary cavity. We evaluated the efficacy and safety of the composite coating in preventing implant-related infections using imaging, hematology, and pathology. In vitro experiments demonstrated that the PCL membrane stably protects encapsulated vancomycin during PBS immersion. The PCL membrane rapidly degraded at a lipase concentration of 0.2 mg/mL. The mPEG750-b-PCL2500 gel ensured stable and sustained vancomycin release, inhibiting bacterial growth. We investigated the antibacterial effect of the 3D-printed titanium material, coated with PCL and loaded with mPEG750-b-PCL2500 hydrogel, using a rabbit Staphylococcus aureus infection model. Imaging, hematology, and histopathology confirmed that our composite antibacterial coating exhibited excellent antibacterial effects and infection prevention, with good safety in trials. Our results indicate that the composite antibacterial coating effectively protects vancomycin in the hydrogel from premature release in the absence of bacterial infection. The outer PCL membrane inhibits bacterial growth and prevents biofilm formation. Upon contact with bacterial lipase, the PCL membrane rapidly degrades, releasing vancomycin for antibacterial action. The mPEG750-b-PCL2500 gel provides stable and sustained vancomycin release, prolonging its antibacterial effects. Our composite antibacterial coating demonstrates promising potential for clinical application.

Safety and effectiveness of dual channels vancomycin administration in the treatment of intracranial infection after severe brain injury surgery.

To observe the clinical efficacy and safety of vancomycin intravenous drip combined with vancomycin intrathecal injection in the treatment of intracranial infection after severe brain injury surgery. From January 2020 to June 2022, 80 patients with intracranial infection after severe brain injury surgery were selected and randomly divided into 2 subgroups; there were 40 patients in each subgroup. All patients were treated with vancomycin. The control subgroup was medicated with intravenous drip, and the observation subgroup was treated through 2 channels (intravenous drip + intrathecal injection), with a course of 7 days. The clinical efficacy, intracranial pressure, infection control time, routine indexes of cerebrospinal fluid (white blood cell count [WBC], glucose content [Glu], and total protein content [Pro]) and the incidence of adverse reactions were contrasted between the 2 subgroups. Versus the control subgroup, the total effective rate in the observation subgroup was notably higher (95.00% vs 77.50%). After treatment, aiming at the intracranial pressure and infection control time, versus the control subgroup (146.20 ±â€…22.37) mmH2O and (9.86 ±â€…1.62) days, the observation subgroup were (125.43 ±â€…18.5) mmH2O and (7.35 ±â€…1.57) days respectively, which were notably lower. After treatment, versus the control subgroup, the concentrations of WBC and Pro in cerebrospinal fluid in the observation subgroup were lower, and the content of Glu was higher. There was no statistical distinction in the incidence of adverse reactions between the 2 subgroups (17.50% vs 10.00%). Two-channel administration of vancomycin can improve the clinical efficacy of internal infection after severe craniocerebral injury, reduce intracranial pressure, and cerebrospinal fluid WBC and Pro levels, and has high safety.

Sequential release of vancomycin and BMP-2 from chitosan/nano-hydroxyapatite thermosensitive hydrogel for the treatment of chronic osteomyelitis.

In this study, we developed scaffolds materials with microspheres to form a double sustained release system.Chitosan/nano-hydroxyapatite (CS-HA) was used as a drug carrier to construct a sustained-release system for Bone morphogenetic protein-2(BMP-2) and Vancomycin (VAN). Furthermore, VAN and BMP-2 loaded microspheres (Ms) were prepared by the emulsion ultrasonic method.The resultant composites were characterized by Scanning electron microscope (SEM), compressive strength, porosity, and biodegradation. The characterization results showed uniform porous and rough surface, enhanced thermal stability, and highest compressive strength ((1.912 ± 0.012) Kpa, the surface of the two microspheres was slightly folded and showed a regular spherical shape.The loading rate of BMP-2 was (59.611 × 10-4 ± 0.023 × 10-4)% and the encapsulation rate was (6.022 ± 0.005)%. The release rate of vancomycin and BMP-2 was 57.194% and 12.968% respectively. Osteogenic differentiation of Bone marrow mesenchymal stem cells (BMSCs) was confirmed by alkaline phosphatase quantification. The deposition of late osteogenic markers (calcium phosphates) detected by Alizarin red, which indicated extracellular matrix mineralization. The results showed that BMP-2/VAN in CS-HA hydrogel successfully achieved the sequential release of the double drugs, which could benefit bone regeneration.

Antibacterial activity of a silver-incorporated vancomycin-modified mesoporous silica against methicillin-resistant Staphylococcus aureus.

Since conventional antibiotics are almost ineffective on methicillin-resistant Staphylococcus aureus (MRSA) strains, designing their antibacterial alternatives is necessary. Besides, the use of vancomycin is applied for specific detection of the bacteria. Silver-incorporated vancomycin-modified mesoporous silica nanoparticles (MSNs@Van@Ag NPs) were designed for detection and treatment of MRSA bacteria. Mesoporous silica nanoparticles (MSNs) were synthesized through the template method, modified with vancomycin, and finally incorporated with silver nanoparticles (Ag NPs). The MSNs@Van@Ag NPs with a homogenously spherical shape, average size of 50-100 nm, surface area of 955.8 m2/g, and thermal stability up to 200°C were successfully characterized. The amount of Ag incorporated into the MSNs@Van@Ag was calculated at 3.9 ppm and the release amount of Ag was received at 2.92 ppm (75%) after 100 h. The in vitro antibacterial susceptibility test showed the MIC of 100 µg mL-1 for MSNs@Van and 50 µg mL-1 for MSNs@Van@Ag, showing in vitro enhanced effect of Ag and vancomycin in the bactericidal process. An in vivo acute pneumonia model was performed and biochemical assays and pathological studies confirmed the nanomedicine's short-term safety for in vivo application. Cytokine assay using ELISA showed that MSN@Van@Ag causes a reduction of pro-inflammatory cytokines and bacterial proliferation leading to alleviation of inflammatory response.

Vancomycin Soaking to Reduce Intraoperative Contamination by Cutibacterium acnes During the Latarjet Procedure.

BACKGROUND: Postoperative infection after the Latarjet procedure, ranging from 1% to 6%, can compromise the functional outcome of young athletes. Cutibacterium acnes is a main pathogen as a consequence of an intraoperative contamination. PURPOSE: To evaluate intraoperative contamination with C. acnes and the effectiveness of the local application of vancomycin during the Latarjet procedure. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This was a single-center study including 75 patients (mean age, 26 years; range, 15-55 years) operated on for anterior shoulder instability with the primary open Latarjet procedure; they underwent the same protocol of skin preparation and preoperative prophylactic antibiotics. Three groups of 25 patients were created and divided sequentially, without the results of each group being known before the end of the study: group A (5 mg/mL of vancomycin), group B (20 mg/mL of vancomycin), and group C (control group with no vancomycin). Swab samples of the coracoid were taken before sectioning the coracoid process (time 1) and after its preparation (time 2). The coracoid was then wrapped in gauze impregnated with different concentrations of vancomycin, except for group C. A final sample (time 3) was taken before screwing the bone block onto the glenoid. All samples were cultured for 21 days, and patients underwent clinical and radiological follow-up for 6 months. RESULTS: The C. acnes contamination rates at times 1, 2, and 3 were 25%, 44%, and 45%, respectively, without significant difference. There was no significant difference between groups A and B with respect to the number of positive cultures at each time point. Of 9 positive cultures at time 1, all were still positive at time 3 in group A, whereas 3 of 5 were negative in group B (P = .027). The rate of C. acnes at time 3 in the control group was higher than that in the 2 other groups (68% vs 44% for group A and 20% for group B; P = .003). Body mass index was the only prognostic factor for a C. acnes-positive culture (26.05 ± 3.39 vs 23.34 ± 2.33; P = .018). No clinical infection was reported at the 6-month postoperative follow-up. CONCLUSION: The rate of C. acnes contamination ranged from 25% to 68% during the open Latarjet procedure in young athletes. Vancomycin reduced the bacterial contamination when it was used at high concentrations in a gauze wrap on the coracoid. The type of C. acnes detected and its clinical implications remain to be studied.

Antibacterial efficacy of antimicrobial peptide-functionalized hydrogel particles combined with vancomycin and oxacillin antibiotics.

The rise of antibiotic resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), requires novel approaches to combat infections. Medical devices like implants and wound dressings are frequently used in conjunction with antibiotics, motivating the development of antibacterial biomaterials capable of exhibiting combined antibacterial effects with conventional antibiotics. This study explores the synergistic antibacterial effects of combining antimicrobial peptide (AMP) functionalized hydrogel particles with conventional antibiotics, vancomycin (VCM) and oxacillin (OXA), against Staphylococcus aureus and MRSA. The AMP employed, RRPRPRPRPWWWW-NH2, has previously demonstrated broad-spectrum activity and enhanced stability when attached to hydrogel substrates. Here, checkerboard assays revealed additive and synergistic interactions between the free AMP and both VCM and OXA against Staphylococcus aureus and MRSA. Notably, the AMP-OXA combination displayed a significant synergistic effect against MRSA, with a 512-fold reduction in OXA's minimum inhibitory concentration (MIC) when combined with free AMP. The observed synergism against MRSA was retained upon covalent AMP immobilization onto the hydrogel particles; however, at a lower rate with a 64-fold reduction in OXA MIC. Despite this, the OXA-AMP hydrogel particle combinations retained considerable synergistic potential against MRSA, a strain resistant to OXA, highlighting the potential of AMP-functionalized materials for enhancing antibiotic efficacy. These findings underscore the importance of developing antimicrobial biomaterials for future medical devices to fight biomaterial-associated infections and reverse antimicrobial resistance.

Novel insights into vancomycin-loaded calcium sulfate and negative pressure wound therapy in preventing infections in open fractures.

BACKGROUND: Open fractures are challenging due to susceptibility to Staphylococcus aureus infections. This study examines the impact of Vancomycin-Loaded Calcium Sulfate (VLCS) and negative pressure wound therapy (NPWT) on macrophage behavior in enhancing healing and infection resistance. Both VLCS and NPWT were evaluated individually and in combination to determine their effects on macrophage polarization and infection resistance in open fractures. METHODS: Through single-cell RNA sequencing, genomic expressions in macrophages from open fracture patients treated with VLCS and NPWT were compared to a control group. The analysis focused on MBD2 gene changes related to macrophage polarization. RESULTS: Remarkable modifications in MBD2 expression in the treatment group indicate a shift towards M2 macrophage polarization. Additionally, the combined treatment group exhibited greater improvements in infection resistance and healing compared to the individual treatments. This shift suggests a healing-promoting atmosphere with improved infection resilience. CONCLUSIONS: VLCS and NPWT demonstrate the ability to alter macrophage behavior toward M2 polarization, which is crucial for infection prevention in open fractures. The synergistic effect of their combined use shows even greater promise in enhancing outcomes in orthopedic trauma care.

Combination of bacteriophages and vancomycin in a co-delivery hydrogel for localized treatment of fracture-related infections.

Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 103 PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes.

Shoulder girdle muscle abscess: Potential routes of spread and surgical management by a dual anterior approach.

BACKGROUND: Spontaneous infections involving muscles in the shoulder girdle are uncommon conditions rarely reported in the literature. The large musculature of shoulder girdle, complex communicating spaces into the periscapular region, and late glenohumeral joint involvement can cause delay in diagnosis of infections involving muscular portion of rotator cuff. The method of surgical drainage with involvement of scapulothoracic and subscapular spaces and prognosis can be challenging. METHODOLOGY: In this descriptive study, we included patients with shoulder girdle muscle abscess and analyzed the spread in the shoulder girdle and arm through various pathways radiologically. Debridement of the abscess in the subscapular muscle and adnexa was done through the dual approach, one with deltopectoral approach for the shoulder girdle and another incision anterior to the latissimus dorsi muscle for inferior subscapular spaces and gravity-dependent drainage of collection. RESULTS: The causative organism Staphylococcus aureus was isolated only in two patients out of four cases. In repeated collections, axillary and suprascapular nerve palsies were commonly encountered. Adequate debridement, antibiotic cover with vancomycin and clindamycin for six weeks, and rehabilitation restored normal functions of the shoulder in three patients. CONCLUSION: Unsuspecting nature of the subscapular abscess and similarities with common shoulder conditions at initial presentation often led to extensive shoulder girdle involvement via subscapular space, subcoracoid recess, and scapulothoracic space to adjacent areas. The dual approach provides adequate access to drain the collections in subscapularis muscle, subscapular spaces, and shoulder girdle. LEVEL OF STUDY: V.

Recent advances in nanostructured delivery systems for vancomycin.

Despite the development of new generations of antibiotics, vancomycin remained as a high-efficacy antibiotic for treating the infections caused by MRSA. Researchers have explored various nanoformulations, aiming to enhance the therapeutic efficacy of vancomycin. Such novel formulations improve the effectiveness of drug cargoes in treating bacterial infections and minimizing the risk of adverse effects. The vast of researches have focuses on enhancing the permeation ability of vancomycin through different biological barriers especially those of gastrointestinal tract. Increasing the drug loading and tuning the drug release from nanocarrier are other important goal for many conducted studies. This study reviews the newest nano-based formulations for vancomycin as a key antibiotic in treating hospitalized bacterial infections.

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Evaluating the role of amino acids and isothermal dry particle coating in modulating buccal permeation of large molecule drug vancomycin.

The formulation and delivery of macromolecules through the oral route pose considerable challenges due to factors such as large molecular weight, pH sensitivity, and limited formulation approaches. This challenge is compounded if the drug is poorly permeable, necessitating innovative drug delivery strategies. Vancomycin, a widely prescribed glycopeptide antibiotic, has an oral bioavailability of less than 10%, leading to predominantly intravenous administration and potential patient discomfort. This study explores the potential of the buccal route as a non-invasive, highly vascularised alternative route of administration, offering a rapid onset of action while bypassing the first-pass metabolism. In this study, vancomycin was coated with L-glutamic acid using an isothermal dry particle coater to modulate permeation through the buccal cell line, TR146. Results confirm significant impact of both amino acid concentration and dry particle coating on the rate and extent of drug permeability. With the introduction of L-glutamic acid and utilisation of the isothermal dry particle coater, vancomycin's permeation profile increased six-fold compared to the control due to the formation of drug ion-pair complex. Imaging studies showed the presence of layered micronized glutamic acid particles on the surface of dry coated vancomycin particles which confirms the role of dry coating and amino acid concentration in modulating drug permeation. Microbiology experiments in Staphylococcus aureus, minimum inhibitory concentration and biofilm disruption studies, provided confirmatory evidence of antimicrobial activity of dry coated glutamic acid-vancomycin ion pair particulate structure. This study demonstrates, for the first-time, buccal delivery of dry coated large molecule drug, vancomycin, through controlled deposition of amino acid using innovative particle coating strategy.

Treatments for pathogen infection rescued 2 patients with renal artery rupture after kidney transplantation: A case report.

RATIONALE: Renal artery rupture due to allograft infection, especially by fungi, is a serious clinical complication that can occur after kidney transplantation, and may lead to graft loss and death. PATIENT CONCERNS: Two kidney recipients from China who developed renal artery rupture at our hospital on 5 days (47-year-old female) and 45 days (39-year-old male) after surgery. DIAGNOSES: The male had immunoglobulin A nephropathy as a primary disease, and experienced a postoperative attack of vascular rejection and mixed infection by Mucor and bacteria. The female had chronic glomerulonephritis as a primary disease, and experienced renal artery rupture near the anastomosis site with infection by fungi and other pathogens. INTERVENTIONS: The male received resection of the implanted kidney and antibiotic therapy with intravenous vancomycin (0.5 g, 2 days) and amphotericin B (530 mg in 33 days). The female received replacing the segment of renal arterial and internal iliac artery by saphenous vein, as well as antibiotic therapy with amphotericin B (320 mg in 8 days). OUTCOMES: The male was recovered and received a second transplantation, while the female was discharged on postoperative day 19. LESSONS: In both patients, prompt surgery and aggressive treatment with an antifungal drug (amphotericin B) and antidrugs led to successful rescue.

Serum and urinary biomarkers of vancomycin-induced acute kidney injury: A prospective, observational analysis.

Vancomycin, a first-line drug for treating methicillin-resistant Staphylococcus aureus infections, is associated with acute kidney injury (AKI). This study involved an evaluation of biomarkers for AKI detection and their comparison with traditional serum creatinine (SCr). We prospectively enrolled patients scheduled to receive intravenous vancomycin for methicillin-resistant S aureus infection. Blood samples for pharmacokinetic assessment and SCr and cystatin C (CysC) measurements were collected at baseline and on days 3, 7, and 10 from the initiation of vancomycin administration (day 1). Urinary biomarkers, including kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin, and clusterin, were collected from days 1 to 7 and adjusted for urinary creatinine levels. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the 42 patients, 6 experienced vancomycin-induced AKI. On day 7, the change from baseline eGFR using CysC (ΔeGFRCysC) showed a stronger correlation with vancomycin area under the curve (r = -0.634, P < .001) than that using SCr (ΔeGFRSCr; r = -0.437, P = .020). ΔeGFRSCr showed no significant correlation with vancomycin pharmacokinetic in patients with body mass index ≥23. The median (interquartile range) level of KIM-1 (µg/mg) was significantly higher in the AKI group (0.006 [0.005-0.008]) than in the non-AKI group (0.004 [0.001-0.005]) (P = .039, Mann-Whitney U test), with area under the receiver operating characteristic curve (95% confidence interval) of 0.788 (0.587-0.990). Serum CysC, particularly in overweight individuals or those with obesity, along with urinary KIM-1 are important predictors of vancomycin-induced AKI. These results may aid in selecting better biomarkers than traditional SCr for detecting vancomycin-induced AKI.

Decreased Kidney Function Explains Higher Vancomycin Exposure in Older Adults.

INTRODUCTION: Older adults face a higher risk of vancomycin-related toxicity given their (patho)-physiological changes, making early management of supratherapeutic exposure crucial. Yet, data on vancomycin exposure in older adults is scarce. This study aims to compare vancomycin concentrations between older and younger patients, emphasizing supratherapeutic concentrations and the effect of patient characteristics. METHODS: This observational retrospective study was conducted in the University Hospital of Leuven (EC Research S65213). We analyzed early (first) vancomycin concentrations between older (≥ 75 years) and younger patients. Multivariable analyses were conducted to evaluate the association between baseline patient characteristics with supratherapeutic exposure (logistic regression), and dose-normalized concentrations (linear regression). RESULTS: We included 449 patients aged ≥ 75 years (median 80) and 1609 aged < 75 years (median 61). In univariable analysis, the first-measured vancomycin concentrations were significantly higher in older adults (p < 0.001), who more frequently reached supratherapeutic concentrations (30.7% versus 21%; p < 0.001). In multivariable analysis, factors associated with supratherapeutic concentrations were decreased the estimated glomerular filtration rate calculated by using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) [odds ratio (OR) of 0.98, confidence interval (CI) 0.97-0.98]. Supratherapeutic concentrations had inverse association with giving lower loading dose (OR of 0.59, CI 0.39-0.90), and lower maintenance dose (OR of 0.45, CI 0.26-0.77). Factors that predicted increased dose-normalized concentrations included decreased eGFRCKD-EPI (coefficient of -0.05, CI -0.06 to -0.04), lower body weight (coefficient of -0.04, CI -0.05 to -0.03), increased blood urea nitrogen (coefficient of 0.02, CI 0.01-0.03), and delayed time to therapeutic drug monitoring (TDM) sampling (coefficient of 0.08, CI 0.06-0.09). CONCLUSIONS: The absence of age as a significant factor in the multivariable analysis suggests that eGFRCKD-EPI mediated the relationship between age and vancomycin exposure. Older adults may benefit more from vancomycin TDM.