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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 MIC 50/90 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 MIC 50/90 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 ., Competing Interests: K.W.G.: research support paid to his institution from Acurx Pharmaceuticals, Paratek Pharmaceuticals, and Merck Inc., and consulting support from Ferring, Inc. A.J.G.L. received research grants paid to her institution from Seres Therapeutics and is a consultant for Ferring Pharmaceuticals. All other authors declare no conflict of interest.

The use of glycopeptide medications may decline in line with the annual decline in methicillin-resistant Staphylococcus aureus (MRSA) detection rates in China. The rate of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA)detection may be impacted by this. However, there is currently a dearth of information on the incidence of hVISA in China. This study aims to analyze the recent epidemiology and molecular characteristics of hVISA strains in Beijing, China. A total of 175 non-duplicate MRSA strains from various infection sites were collected from a medical center between January 2018 and May 2023 and underwent molecular typing and susceptibility testing (Vitek2). Vancomycin and teicoplanin MICs were also evaluated by standard broth microdilution method and agar dilution method, respectively. Isolates growing on screening agar (BHIV4 and BHIT5, brain heart infusion agar containing 4 μg/ml vancomycin and 5 μg/ml teicoplanin, respectively) were characterized further by analysis of macro-Etest (MET) and population analysis profiling with area under the curve (PAP-AUC). The proportion of hVISA among MRSA isolates was 8.6 %. BHIT5 could select all hVISA strains while BHIV4 and MET only selected two hVISA strains. Compared with vancomycin- susceptible Staphylococcus aureus (VSSA), hVISA isolates were less susceptible to erythromycin and clindamycin. In addition, hVISA frequency was MIC-independent despite using different detection methods. In total, 11 types of STs, 28 types of spa typing, four types of SCCmec typing, and two types of agr typing were identified and the predominant type in both MRSA and hVISA isolates was ST239-t030-SCCmecIII-agr I. The analysis of biofilm formation, growth, and virulence genes in hVISA strains revealed sparse information. The dataset presented in this study provided the prevalence and molecular characteristics of hVISA in hospital settings and the combination of BHIT5 and PAP-AUC may identify hVISA efficiently. The result of genotyping suggested the genotype of hVISA was mainly consistent with that of local MRSA. Additional studies on the characteristics of hVISA strains were necessary., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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 Ca 2+ , 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., (© 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Enterococci are opportunistic pathogens with plastic genomes that evolve, acquire, and transmit antimicrobial-resistant determinants such as vancomycin resistance clusters. While vancomycin-resistant enterococci (VRE) have emerged as successful nosocomial pathogens, the mechanism by which vancomycin-susceptible enterococci (VSE) transform to VRE in hospitalized patients remains understudied., Methods: Genomes of Enterococcus faecium from two critically ill hospitalized patients subjected to multiple antibiotic therapies, including broad-spectrum antibiotics, were investigated. To identify mechanisms of resistance evolution, genomes of vancomycin-susceptible and -resistant isolates were compared., Results: While VSE isolates were initially identified, VRE strains emerged post-vancomycin therapy. Comparative genomics revealed horizontal transmission of mobile genetic elements containing the Tn1549 transposon, which harbours the vanB-type vancomycin resistance gene cluster. This suggests that broad-spectrum antibiotic stress promoted the transfer of resistance-conferring elements, presumably from another gut inhabitant., Conclusion: This is one of the first studies investigating VSE and VRE isolates from the same patient. The mechanism of transmission and the within-patient evolution of vancomycin resistance via mobile genetic elements under antibiotic stress is illustrated. Our findings serve as a foundation for future studies building on this knowledge which can further elucidate the dynamics of antibiotic stress, resistance determinant transmission, and interactions within the gut microbiota., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Venous access device-related bloodstream infection (VAD-BSI) with coagulase-negative staphylococci (CoNS) is a common complication after allogeneic hematopoietic cell transplantation (alloHCT). Standard systemic antimicrobial therapy for uncomplicated VAD-BSI with methicillin-resistant CoNS consists of intravenous (IV) vancomycin (vanco). This requires hospitalization, needs new competent venous access, exposes patients to potential toxicity (mainly renal) and increases the risk of commensal flora dysbiosis with selection of vanco-resistant enterococci. Combined with VAD management (removal or antibiotic locks), oral minocycline (mino) has been evaluated as an alternative systemic therapy for the treatment of uncomplicated VAD-BSIs with CoNS at our center, primarily when the reference treatment with IV vanco was not possible (renal failure or allergy) or when hospitalization was refused by patients. Here, we retrospectively report our single center experience with this mino-based approach., Patients and Methods: From January 2012 to December 2020, 24 uncomplicated VAD-BSIs with CoNS in 23 alloHCT patients were treated with oral mino as systemic antibiotic therapy in combination with VAD management. VAD were implantable ports (n = 17), tunneled catheter (n = 1) or PIC-lines (n = 6). Staphylococci were S. epidermidis (n = 21) or S. haemolyticus (n = 3). Mino was administered with a loading dose of 200 mg followed by 100 mg BID for 7-14 days. For 8 VAD-BSIs, patients were initially treated with IV vanco for the first 1-3 days followed by oral mino, while 16 VAD-BSIs were treated with oral mino as the sole antimicrobial agent for systemic therapy. VAD management consisted of catheter removal (for tunneled catheters and PIC-lines, n = 7) or antibiotic locks with vanco (n = 15) or gentamicin (n = 2) administered at least 3 times a week for 14 days (for ports)., Results: Overall, clearance of bacteremia (as assessed by negativity for the same CoNS of surveillance peripheral blood cultures drawn between day+ 3 and +30 after initiation of systemic therapy) was achieved in all but 1 patient (with port) who had persistent bacteremia at day +9. No complication such as suppurative thrombophlebitis, endocarditis, distant foci of infection or BSI-related death was observed in any patient during the 3-month period after initiation of treatment. Regarding the 17 port-BSI cases for which VAD conservative strategy was attempted, failure of 3-month VAD preservation was documented in 7/17 cases and 3-month recurrence of VAD-BSI was observed in 3/17 cases (with 1 patient with cellulitis). Treatment with mino was well tolerated except for a mild skin rash in one patient., Conclusion: Further prospective studies are needed to evaluate efficacy and safety of this approach., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

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.

Background: Intravenous (IV) vancomycin is commonly used to treat a variety of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The practice of administering a single dose of IV vancomycin prior to emergency department (ED) discharge may be clinically ineffective and foster antimicrobial resistance. Furthermore, this practice introduces an unnecessary infection risk along with preventable adverse effects while potentially increasing ED length of stay (LOS). There is a paucity of literature identifying patient characteristics and objective findings in this patient population, which may foster future antimicrobial stewardship initiatives in the ED., Methods: This was a single-center, retrospective, descriptive analysis of adult patients seen in the ED between January 2020 and January 2023 who received a single dose of IV vancomycin and were subsequently discharged from the ED without hospital admission. Information was collected on patient demographics and select comorbidities, vancomycin indication and dosing, ED LOS, initial vitals and labs, concomitant antibiotics administered, culture results, 30-day return ED visits and admissions, and antibiotics prescribed at ED discharge., Results: A total of 295 patients met inclusion criteria. A total of 32.1% of patients met SIRS criteria. The most commonly selected order indication for IV vancomycin was "skin and skin structure infection" (41%). A total of 86.1% of patients received concomitant antibiotics in the ED and only 54.6% of patients were prescribed oral antibiotics at ED discharge. A total of 80% of patients had at least one culture obtained during the ED visit. In those who had at least one culture obtained, 78.4% of patients had negative cultures and 4.2% of patients had MRSA positive cultures, with MRSA skin cultures being the most common (3.1%). Return ED visits and admissions within 30 days were not statistically significantly different between patients who did and did not receive oral antibiotics at ED discharge., Conclusions: Despite a lack of clinical efficacy reported in prior literature and the potential risks, administration of a one-time dose of IV vancomycin prior to ED discharge is commonly encountered in clinical practice. There are opportunities for enhanced antimicrobial stewardship related to IV vancomycin use in the ED. Areas of future focus include the utilization of oral antimicrobials when clinically appropriate, particularly for skin and soft tissue infections, and clarification of antibiotic allergies., Competing Interests: Declaration of Competing Interest The authors have no disclosures or financial conflicts of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: In the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs), vancomycin stands as the prevalent therapeutic agent. Daptomycin remains an alternative antibiotic to treat MRSA BSIs in cases where vancomycin proves ineffective. However, studies have conflicted on whether daptomycin is more effective than vancomycin among patients with MRSA BSI., Objective: To compare the effectiveness of daptomycin and vancomycin for the prevention of mortality among adult patients with MRSA BSI., Methods: Systematic searches of databases were performed, including Embase, PubMed, Web of Science, and Cochrane Library. The Newcastle Ottawa Scale (NOS) and Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) were used to assess the quality of individual observational and randomized control studies, respectively. Pooled odd ratios were calculated using random effects models., Results: Twenty studies were included based on a priori set inclusion and exclusion criteria. Daptomycin treatment was associated with non-significant lower mortality odds, compared to vancomycin treatment (OR = 0.81; 95% CI, 0.62, 1.06). Sub-analyses based on the time patients were switched from another anti-MRSA treatment to daptomycin demonstrated that switching to daptomycin within 3 or 5 days was significantly associated with 55% and 45% decreased odds of all-cause mortality, respectively. However, switching to daptomycin any time after five days of treatment was not significantly associated with lower odds of mortality. Stratified analysis based on vancomycin minimum inhibitory concentration (MIC) revealed that daptomycin treatment among patients infected with MRSA strains with MIC≥1 mg/L was significantly associated with 40% lower odds of mortality compared to vancomycin treatment., Conclusion: Compared with vancomycin, an early switch from vancomycin to daptomycin was significantly associated with lower odds of mortality. In contrast, switching to daptomycin at any time only showed a trend towards reduced mortality, with a non-significant association. Therefore, the efficacy of early daptomycin use over vancomycin against mortality among MRSA BSIs patients may add evidence to the existing literature in support of switching to daptomycin early over remaining on vancomycin. More randomized and prospective studies are needed to assess this association., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode., Methods: We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile, and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin., Results: Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P = .195) and rCDI (3.3% vs 4.0%; P > .99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI., Conclusions: In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA., Clinical Trials Registration: www.clinicaltrials.gov (NCT02692651)., Competing Interests: Potential conflicts of interest. K. R. is supported, in part, by an investigator-initiated grant from Merck & Co, Inc, and he has consulted for Seres Therapeutics, Inc, Rebiotix, Inc, and Summit Therapeutics, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation., Methods: A multidisciplinary committee created an infectious diseases DOOR endpoint customized for HABP/VABP, incorporating infectious complications, serious adverse events, and mortality. We applied this to 2 previously completed, large randomized controlled trials for HABP/VABP. ZEPHyR compared vancomycin to linezolid and VITAL compared linezolid to tedizolid. For each trial, we evaluated the DOOR distribution and probability, including DOOR component and partial credit analyses. We also applied DOOR in subgroup analyses., Results: In both trials, the HABP/VABP DOOR demonstrated similar overall clinical outcomes between treatment groups. In ZEPHyR, the probability that a participant treated with linezolid would have a more desirable outcome than a participant treated with vancomycin was 50.2% (95% confidence interval [CI], 45.1%--55.3%). In VITAL, the probability that a participant treated with tedizolid would have a more desirable outcome than a participant treated with linezolid was 48.7% (95% CI, 44.8%-52.6%). The DOOR component analysis revealed that participants treated with tedizolid had a less desirable outcome than those treated with linezolid when considering clinical response alone. However, participants with decreased renal function had improved overall outcomes with tedizolid., Conclusions: The HABP/VABP DOOR provided more granular information about clinical outcomes than is typically presented in clinical trials. HABP/VABP trials would benefit from prospectively using DOOR., Competing Interests: Potential conflicts of interest. H. W. B. declares consulting fees from Antimicrobial Agents and Chemotherapy/American Society for Microbiology (ASM), Sanford Guide, and ID Clinics of North America/Elsevier; royalties from Sanford Guide; payment or honoraria from Grand Rounds at Temple; Finland Award for IDWeek Lecture travel; and role with travel reimbursed as Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (PACCARB) Voting Member and Board of Trustees, College of the Holy Cross. D. C. reports honoraria from ARLG, SimBioSys, AstraZeneca, Apellis Pharmaceutical, Kinnate Biopharma, MaxisIT Clinical Sciences, Pfizer, Parexel, Health Literacy Media, Incyte, American Society of Clinical Oncology, and Aster Insights, all unrelated to this work; and consulting fees from AstraZeneca, Incyte, Apellis Pharmaceuticals, Kinnate Biopharma, Maxis Health, Parexel, Health Literacy Media (nonprofit), and SimBioSys; reimbursement for personal expenses for attending meetings and/or travel from Aster Insights and the American Society of Clinical Oncology (ASCO); participation with honorarium to author on a data and safety monitoring board (DSMB) or advisory board for ASCO; a role as unpaid volunteer for the Metastatic Breast Cancer Alliance; and a role with honorarium to author from ORIEN Patient Advisory Council. H. F. C. reports grant funding from NIH; royalties from Sanford Guide to Antimicrobial Therapy; payment from The George Washington University for ID board review course lectures; participation in a DSMB for Merck; and stock in Merck and Moderna. S. B. D. reports research funding for clinical research studies from Gilead, Regeneron, Pfizer, F2G, Chan Zuckerberg Initiative Biohub, and NIH/NIAID; payments for clinical event adjudication committees from Basilea, Duke Clinical Research Institute, and Shionogi; a patent pending for Mif agonists (patent US20100143379A1); money for travel to conference from the Infectious Diseases Society of America (IDSA); and consulting fees from Genentech and Janssen/Johnson & Johnson (J&J); and leadership or fiduciary roles with IDSA Antibacterial Resistance Committee, California Department of Public Health Healthcare Associated Infections Advisory Committee, and the ARLG Innovations Group, Laboratory Center, Mentorship Committee, Gram Positive Committee, and Immunosuppressed Host Group. S. R. E. reports grant funding from NIH (NIAID, National Cancer Institute, National Heart, Lung, and Blood Institute), Centers for Disease Control and Prevention (CDC), and De Gruyter (Editor-in-Chief of Statistical Communications in Infectious Diseases); royalties from Taylor & Francis; consulting fees from Genetech, AstraZeneca, Takeda, Microbiotix, J&J, Endologix, ChemoCentryx, Becton Dickenson, Atricure, Roivant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute (IDDI), SVB Leerink, Medtronic, Regeneron, Wake Forest University, Recor, Janssen, and IDDI; payments from lectures from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); support for attending meetings from FDA; and participation on DSMBs for NIH, Breast International Group, University of Pennsylvania, Washington University, Duke University, Roche, Pfizer, Takeda, Akouous, Appelis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, AbbVie, GSK, Eli Lilly, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Candel, Novartis, and Advantagene; and being an unpaid board member for the American Statistical Association, Society for Clinical Trials, and Frontier Science Foundation. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, The Medicines Co, MedImmune, Bayer, Basilea, Affinergy, Janssen, ContraFect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, and Roche; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, ContraFect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from IDSA for his service as Associate Editor of Clinical Infectious Diseases; and a patent pending in sepsis diagnostics. H. L.-T. is an employee of Pfizer and holds stock in Pfizer. C. H. receives stock dividends from GlaxoSmithKline. T. L. H. declares grant funding from NIH and Karius; royalties from UpToDate; consulting fees from Basilea Pharmaceutica, Affinivax, Lysovant, Aridis, and Pfizer; and participation on DSMB for platform trial for SNAP Trial and advisory board for Basilea. J. H.-A. reports grant funding from NIH and CDC; and payment from IDSA (reviewing IDSA/Clinical Infectious Diseases supplement), ARLG (for speaking at IDWeek dinner and Texas Medical Center Antimicrobial Resistance and Stewardship Conference conference), and Society for Healthcare Epidemiology of America (SHEA) (for speaking at SHEA Spring Conference). S. N. is an employee of J&J and holds stock in J&J; received support for travel to meetings paid by employer; and participated as unpaid member of a scientific advisory committee of Global Antibiotic Research and Development Partnership. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Little is known about efficacy and safety of ethanol lock therapy (ELT) to treat totally implantable venous access device (TIVAD) infections. The objective of this trial was to evaluate the effectiveness and safety profile of a local treatment with ELT without removal for TIVAD infection due to coagulase-negative staphylococci., Methods: We performed a prospective, multicenter, double-blind, randomized clinical trial comparing the efficacy of 40% ELT versus vancomycin lock therapy (VLT) in TIVAD infections due to coagulase-negative staphylococci, complicated or not by bloodstream infection., Results: Thirty-one patients were assigned to the ELT group and 30 to the VLT arm. Concomitant bacteremia was present in 41 patients (67.2%). Treatment success was 58.1 % (18 of 31) for the ELT arm and 46.7% (14 of 30) for the VLT arm (p = 0.37). The overall treatment success was 52.5% (32). The risk of treatment failure due to uncontrolled infections, superinfections, and mechanical complications did not differ significantly between participants receiving ELT (13 out of 31 [42%]) and those receiving VLT (16 out of 30 [53%]) with a hazard ratio of 0.70 (p = 0.343; 95% CI [0.34-1.46], Cox model). Catheter malfunctions were significantly more frequent in the ELT arm (11 patients versus 2 in the VLT group, p = 0.01)., Conclusions: We found an overall high rate of treatment failure that did not differ between the ELT arm and the VLT arm. TIVAD removal must be prioritized to prevent complications (uncontrolled infections, superinfections, and catheter malfunctions) except in exceptional situations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Because of the established path of bacterial entry and contamination-associated mechanisms, grade 3 open orthopedic fractures represent a substantial infection risk. The Eastern Association for the Surgery of Trauma (EAST) guidelines recommended covering Staphylococcus aureus and adding aminoglycoside gram-negative coverage. Local institutional guidelines rely on ceftriaxone for gram negative coverage and add methicillin-resistant Staphylococcus aureus coverage with vancomycin. Patients and Methods: The electronic health records of adults admitted for a grade 3 open fracture between January 1, 2016, and October 31, 2021, were retrospectively reviewed. Patients who received cefazolin and gentamicin (CZ+GM) or ceftriaxone and vancomycin (CRO+VA) as prophylaxis were included. We recorded the rate of a composite treatment failure outcome of receipt of antibiotic agents, infection-related hospitalization, or subsequent debridement for injury-site skin and soft tissue infection or osteomyelitis. The presence of acute kidney injury (AKI) was also evaluated. Results: There were 65 patients included in the CZ+GM group and 53 patients in the CRO+VA group. Patients in the CZ+GM group were younger (mean 42.6 compared with 50.6 years; p = 0.02). Otherwise, there were no significant differences between groups' demographics, mechanism and site of injury, timeline of care, or surgical interventions. More patients in the CZ+GM arm met the composite treatment failure outcome, but it was not statistically significant (45% vs. 32%; p = 0.2). There were similar rates of treatment failure at 30 days (21% vs. 26%; p = 0.5) and for only osteomyelitis (8% vs. 9%; p = 1). Conclusions: The trend in numerically lower treatment failure rates in the CRO+VA group across outcomes provides sufficient evidence to continue the current local recommendations. Given our sample size, type 2 error may have occurred, and studies with greater power should analyze this question.

A vancomycin-sparing guideline for suspected late-onset sepsis helped reduce vancomycin usage in our level-4 neonatal intensive care unit. Significant reduction in overall vancomycin use, with its likely unit-wide beneficial downstream effects, may need to be measured against the rare case of methicillin-resistant Staphylococcus aureus infection and delayed effective therapy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Peritonitis, a serious complication of peritoneal dialysis (PD), can be caused by opportunistic pathogens like Micrococcus species on rare occasions. We present a case of Micrococcus sp peritonitis in a 55-year-old female with end-stage kidney disease on continuous cycling peritoneal dialysis for one year who presented with cloudy effluent. Initial treatment against Micrococcus sp with vancomycin, gentamicin, and prophylactic oral nystatin was successful. However, one month later, the patient presented with abdominal pain and dialysate culture again grew Micrococcus sp. Treatment with vancomycin was unsuccessful in resolving culture positivity. The patient was transitioned to hemodialysis for non-medical reasons and then was later restarted on PD without further peritonitis episodes. Micrococcus sp peritonitis in PD poses treatment challenges due to limited guidelines. Intraperitoneal vancomycin is commonly used to target Micrococcus isolates although there is a high incidence of treatment failure. This case report highlights the need for continued reporting to enhance identification, prevention, and patient outcomes in Micrococcus sp peritonitis during PD.

Bloodstream infections caused by vancomycin-resistant enterococci are increasingly reported and a consensus therapy does not exist. Oritavancin has shown good antimicrobial activity against VRE, but its use is mainly limited to skin, soft tissue, and/or bone infections. Fosfomycin is increasingly used for enterococcal infections (including bloodstream infections and endocarditis) as a partner drug given its anti-biofilm and synergistic properties. Recently in vitro and in vivo synergism between oritavancin and fosfomycin against VRE isolates has been demonstrated. Herein we report the case of a hematologic patient with a VRE bloodstream infection successfully treated with oritavancin and fosfomycin as sequential treatment.

A carbon fiber-reinforced polyetheretherketone (CFR/PEEK) hip stem with a special antibiotic elution mechanism is under development to treat periprosthetic joint infection (PJI). The antibiotic elution characteristics of intramedullary implants were experimentally investigated, and the efficacy of revision surgery using a therapeutic stem in treating ovine PJI was examined. To evaluate elution characteristics, the intramedullary vancomycin-loaded CFR/PEEK cylindrical implants were inserted in the distal femur of nine sheep, and the vancomycin elution rate was measured at 2, 7, and 21 days. To evaluate therapeutic efficacy, the PJI model with staphylococcus aureus was attempted to create for five sheep. Moreover, the therapeutic vancomycin-loaded CFR/PEEK stem was implanted during one-stage revision surgery. Three weeks after revision surgery, the treatment efficacy was evaluated based on bacterial cultures and wound findings. In addition, the vancomycin elution rate from the stem was measured. On average, the cylindrical implants eluted approximately 70% vancomycin in 21 days. Of the five sheep attempting to create a PJI model, three were successfully infected with S. aureus as intended for verification of treatment efficacy. In all three joints, negative bacterial cultures and no purulence were observed 3 weeks after revision surgery. The vancomycin elution rates from the stems were >70%. Efficient elution of vancomycin was confirmed by the experimental implant inserted into the bone marrow and the stem in actual PJI treatment. Using a novel therapeutic stem with an antibiotic elution mechanism in one-stage revision surgery, successful treatment was demonstrated in all S. aureus-induced PJIs., (© 2023 Orthopaedic Research Society.)

Objective: Chronic prosthetic joint infection patients who fail conventional two-stage revision surgery are an especially difficult to treat patient population. Consequently, the objective of this study was to investigate the safety and long-term effectiveness of adjuvant intra-articular vancomycin therapy in conjunction with two-stage revision knee arthroplasties for recalcitrant Staphylococcal prosthetic joint infections., Methods: This was an observational cohort study of twelve patients with recalcitrant Staphylococcal prosthetic joint infections of the knee which had failed previous revision surgeries. Each patient subsequently underwent two-stage revision with placement of Hickman catheters to deliver intra-articular vancomycin therapy. In addition, systemic antibiotic therapy was administered for 6 weeks, and long-term follow-up was evaluated then for 5 years., Results: Seventy-five percent of the cohort have had no recurrence of their infections at 5 years. Two patients formed fistulas requiring above the knee amputations, and three patients had acute kidney injury. All patients had maximum measurable serum vancomycin trough levels that ranged from 6.1 to 93.6 mcg/mL., Conclusion: The aggressive protocol used in this cohort with repeat two-stage revision surgery, intra-articular vancomycin and systemic antibiotics was able to prevent recurrence of infection in most patients, but higher than expected rates of acute kidney injury were observed in this study. Therefore, while intra-articular vancomycin therapy may have some effectiveness in treating recalcitrant prosthetic joint infections, its ability to eradicate all bacterial niduses is unproven, and clinicians should be cognizant of potential adverse events that can occur with this therapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Enterococcus faecalis is a common cause of healthcare-associated infections. Its resistance to linezolid, the antibiotic of last resort for vancomycin-resistant enterococci, has become a growing threat in healthcare settings., Methods: We analyzed the data of E. faecalis isolates from 26 medical institutions between 2018 and 2020 and performed univariate and multivariate logistic regression analyses to determine the independent predictors for linezolid-resistant E. faecalis (LREFs). Then, we used the artificial neural network (ANN) and logistic regression (LR) to build a prediction model for linezolid resistance and performed a performance evaluation and comparison., Results: Of 12,089 E. faecalis strains, 755 (6.25%) were resistant to linezolid. Among vancomycin-resistant E. faecalis, the linezolid-resistant rate was 24.44%, higher than that of vancomycin-susceptible E. faecalis (p < 0.0001). Univariate and multivariate regression analyses showed that gender, age, specimen type, length of stay before culture, season, region, GDP (gross domestic product), number of beds, and hospital level were predictors of linezolid resistance. Both the ANN and LR models constructed in the study performed well in predicting linezolid resistance in E. faecalis, with AUCs of 0.754 and 0.741 in the validation set, respectively. However, synthetic minority oversampling technique (SMOTE) did not improve the prediction ability of the models., Conclusion: E. faecalis linezolid-resistant rates varied by specimen site, geographic region, GDP level, facility level, and the number of beds. At the same time, community-acquired E. faecalis with linezolid resistance should be monitored closely. We can use the prediction model to guide clinical medication and take timely prevention and control measures., (© 2023. The Author(s).)

Background: Infection with vancomycin-resistant Enterococcus (VRE) in liver transplant recipients (LTR) has been associated with extended hospital stays, increased readmission rates, graft failure, and death. A tailored perioperative surgical prophylaxis regimen targeting VRE may reduce postoperative infections in VRE-colonized patients. This study investigated the outcomes of perioperative daptomycin in this patient population., Methods: This retrospective, single-center cohort study included LTR ≥ 18 years old who were VRE-colonized from June 2018 to November 2022. VRE colonization was identified by a VRE rectal swab screen or a positive VRE culture prior to transplant. Two groups were analyzed: daptomycin versus no daptomycin. All LTR received perioperative piperacillin-tazobactam for 24 h. If VRE-colonized, one dose of daptomycin (6 mg/kg) was given pre- and postoperatively. Demographics, clinical characteristics, risk factors for VRE infection, and daptomycin dose were collected. The primary outcome was VRE infection at 14 days and 90 days post-transplant., Results: There were 36 VRE-colonized LTR; 19 received daptomycin and 17 did not. Baseline characteristics and risk factors for VRE infection were similar between groups. More VRE infections occurred in the no daptomycin group within 14 days post-transplant (24% vs. 0%, p = .04), but at 90 days posttransplant there was no significant difference (29% vs. 16%, p = .43). The average daptomycin dose was 7.1 mg/kg., Conclusion: Perioperative daptomycin reduced the rate of VRE infections in VRE-colonized LTR within 14 days posttransplant but not at 90 days. Future studies should evaluate if higher doses and/or longer duration of perioperative daptomycin can reduce VRE infections beyond 14 days post-transplant., (© 2023 Wiley Periodicals LLC.)

Background: The effect of systemic treatment of ventilator-associated pneumonia (VAP) with telavancin, a semisynthetic lipoglycopeptide with good penetration in vitro biofilms, has not been tested in vivo during mechanical ventilation. This study examined the efficacy of telavancin compared with linezolid against endotracheal tube (ETT) biofilms in a porcine model of methicillin-resistant Staphylococcus aureus (MRSA) VAP., Methods: VAP was induced in 18 pigs by instilling 10 7 colony-forming units (CFU/mL) of an MRSA strain susceptible to telavancin and linezolid into each pulmonary lobe. Randomization into three groups was done at pneumonia diagnosis: control (IV glucose 0.5% solution q24); linezolid (10 mg/kg q12) and telavancin groups (22.5 mg/kg q24). After 72 h of MV, data regarding bronchoalveolar lavage (BAL), tracheal aspirate (TA), ETT MRSA biofilm load and thickness measured by scanning electron microscopy were obtained., Results: All 18 pigs completed the study. MRSA was isolated in 100% of ETTs from the control and linezolid groups and in 67% from the telavancin group. Telavancin treatment presented a lower MRSA load compared to the control and linezolid treatments (telavancin median [interquartile range (IQR)] = 1.94 [0.00-5.45], linezolid 3.99 [3.22-4.68] and control 4.93 [4.41-5.15], P = 0.236). Telavancin treatment also resulted in the lowest biofilm thickness according to the SEM (4.04 [2.09-6.00], P < 0.001). We found a positive correlation between ETT and BAL load (rho = 0.511, P = 0.045)., Conclusions: In our VAP model, systemic telavancin treatment reduced ETT MRSA occurrence, load, and biofilm thickness. Our findings may have a bearing on ICU patients' clinical outcomes., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Vancomycin is often initiated in hospitalized patients; however, it may be unnecessary or continued for longer durations than needed. Oversight of all vancomycin orders may not be feasible with widespread prescribing and strategies to enlist other clinicians to serve as stewards of vancomycin use are needed. We implemented 2 sequential interventions: a protocol in which the pharmacist orders MRSA nasal swab followed by a protocol requiring approval from pharmacists to continue vancomycin for >72 hours., Methods: In this single-center, retrospective, quasi-experimental study, we evaluated vancomycin use after implementation of a pharmacy-driven MRSA nasal-swab ordering protocol and a vancomycin 72-hour restriction protocol. The primary outcome was the change in the standardized antibiotic administration ratio (SAAR) for antibacterial agents for resistant gram-positive infections. We also evaluated the impact on antibiotic utilization., Results: Following the MRSA swab protocol, the SAAR decreased from 1.26 to 1.13 ( P < .001; 95% confidence interval [CI], 1.16-1.25). After the 72-hour approval process, the SAAR was 0.96 ( P < .001; 95% CI, 1.0-1.12). Vancomycin utilization decreased from 138.9 to 125.3 days of therapy per 1,000 patient days following the MRSA swab protocol ( P < .001) and to 112.7 ( P < .001) following the 72-hour approval protocol. Interrupted time-series analysis identified a similar rate of decline in utilization following the 2 interventions (-0.3 and -0.5; P = .16). Both interventions combined resulted in a significant reduction (-1.5; P < .001)., Conclusion: Implementation of a pharmacist-driven MRSA nasal-swab ordering protocol, followed by a 72-hour approval protocol, was associated with a significant reduction in the SAAR for antibiotics used in the treatment of resistant gram-positive infections and a reduction in vancomycin utilization. Leveraging the oversight of primary service clinical pharmacists through these protocols proved to be an effective strategy.

Objectives: Incidence and risk factors for recurrent Clostridioides difficile infection (rCDI) are well established in adults, though data are lacking in pediatrics. We aimed to determine incidence of and risk factors for rCDI in pediatrics., Methods: This retrospective cohort study of pediatric patients was conducted at 3 tertiary-care hospitals in Canada with laboratory-confirmed CDI between April 1, 2012, and March 31, 2017. rCDI was defined as an episode of CDI occurring 8 weeks or less from diagnostic test date of the primary episode. We used logistic regression to determine and quantify risk factors significantly associated with rCDI., Results: In total, 286 patients were included in this study. The incidence proportion for rCDI was 12.9%. Among hospitalized patients, the incidence rate was estimated at 2.6 cases of rCDI per 1,000 hospital days at risk (95% confidence interval [CI], 1.7-3.9). Immunocompromised patients had higher incidence of rCDI (17.5%; P = .03) and higher odds of developing rCDI independently of antibiotic treatment given for the primary episode (odds ratio [OR], 2.31; 95% CI, 1.12-5.09). Treatment with vancomycin monotherapy did not show statistically significant protection from rCDI, independently of immunocompromised status (OR, 0.33; 95% CI, 0.05-1.15])., Conclusions: The identification of increased risk of rCDI in immunocompromised pediatric patients warrants further research into alternative therapies, prophylaxis, and prevention strategies to prevent recurrent disease burden within these groups. Treatment of the initial episode with vancomycin did not show statistically significant protection from rCDI.

BACKGROUND Peritonitis is a complication associated with peritoneal dialysis (PD), which carries a significant morbidity and mortality risk. Empiric therapy must include coverage of gram-positive organisms; vancomycin is a recommended treatment option, particularly when MRSA infection is a risk. Vancomycin is cumbersome for patients, requiring therapeutic drug monitoring and re-administration by a healthcare provider. Dalbavancin, administered as a one-time intravenous dose, is a convenient potential treatment option for PD patients to cover gram-positive organisms without the need for routine drug monitoring. CASE REPORT We present 2 patients effectively treated with dalbavancin for infectious peritonitis. The first patient, a 73-year-old woman with end-stage renal disease (ESRD) on PD, presented to the hospital with fever, elevated white blood cells (WBCs), and cloudy peritoneal fluid with elevated nucleated cell counts (88% neutrophils). This patient was given 1 dose of 1500 mg IV dalbavancin. Within 3 days, her fever resolved, WBCs returned to normal, and peritoneal fluid results improved. The second patient was a 36-year-old woman presenting to an outpatient clinic with abdominal pain and cloudy peritoneal fluid with elevated nucleated cell counts (53% neutrophils) treated with dalbavancin 1500 mg IV once. Within 4 days, this patient's pain had resolved, and peritoneal fluid results returned to baseline. No adverse effects were noted for either patient. CONCLUSIONS These cases illustrate the potential of dalbavancin as a convenient option for patients with PD-associated peritonitis. Both patients demonstrated rapid and complete response to a single dose of dalbavancin without complications. Further prospective studies are needed to establish dalbavancin as an option for peritonitis.

Background: The perioperative antibiotic prophylaxis with 1st or 2nd generation cephalosporins is evidence-based in orthopedic surgery. There are, however, situations with a high risk of prophylaxis-resistant surgical site infections (SSI)., Methods: We perform a superiority randomized controlled trial with a 10% margin and a power of 90% in favor of the broad-spectrum prophylaxis. We will randomize orthopedic interventions with a high risk for SSI due to selection of resistant pathogens (open fractures, surgery under therapeutic antibiotics, orthopedic tumor surgery, spine surgery with American Society of Anesthesiologists (ASA) score ≥ 3 points) in a prospective-alternating scheme (1:1, standard prophylaxis with cefuroxime versus a broad-spectrum prophylaxis of a combined single-shot of vancomycin 1 g and gentamicin 5 mg/kg parenterally). The primary outcome is "remission" at 6 weeks for most orthopedic surgeries or at 1 year for surgeries with implant. Secondary outcomes are the risk for prophylaxis-resistant SSI pathogens, revision surgery for any reason, change of antibiotic therapy during the treatment of infection, adverse events, and the postoperative healthcare-associated infections other than SSI within 6 weeks (e.g., urine infections or pneumonia). With event-free surgeries to 95% in the broad-spectrum versus 85% in the standard prophylaxis arm, we need 2 × 207 orthopedic surgeries., Discussion: In selected patients with a high risk for infections due to selection of prophylaxis-resistant SSI, a broad-spectrum combination with vancomycin and gentamycin might prevent SSIs (and other postoperative infections) better than the prophylaxis with cefuroxime., Trial Registration: ClinicalTrial.gov NCT05502380. Registered on 12 August 2022. Protocol version: 2 (3 June 2022)., (© 2024. The Author(s).)

Introduction: Ventilator-associated pneumonia (VAP) is a prominent cause of morbidity and mortality in intensive care unit (ICU) patients. Due to the increase in Methicillin resistant Staphylococcus aureus infection, it is important to consider other more effective and safer alternatives compared to vancomycin. This motivates evaluating whether the use of an apparently more expensive drug such as linezolid can be cost-effective in Colombia., Methods: A decision tree was used to simulate the results in terms of the cost and proportion of cured patients. In the simulation, patients can receive antibiotic treatment with linezolid (LZD 600 mg IV/12 h) or vancomycin (VCM 15 mg/kg iv/12 h) for 7 days, patients they can experience events adverse (renal failure and thrombocytopenia). The model was analyzed probabilistically, and a value of information analysis was conducted to inform the value of conducting further research to reduce current uncertainties in the evidence base. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of US$5180., Results: The mean incremental cost of LZD versus VCM is US$-517. This suggests that LZD is less costly. The proportion of patients cured when treated with LZD compared with VCM is 53 vs. 43%, respectively. The mean incremental benefit of LZD versus VCM is 10 This position of absolute dominance (LZD has lower costs and higher proportion of clinical cure than no supplementation) is unnecessary to estimate the incremental cost-effectiveness ratio. There is uncertainty with a 0.999 probability that LZD is more cost-effective than VCM. Our base-case results were robust to variations in all assumptions and parameters., Conclusion: LNZ is a cost-effective strategy for patients, ≥ 18 years of age, with VAP in Colombia- Our study provides evidence that can be used by decision-makers to improve clinical practice guidelines., (© 2024. The Author(s).)

Objective: By reviewing the literature analyzing vancomycin powder for preventive surgery, the effect of this method on reducing the infection rate after TJA was systematically evaluated to provide a basis for future clinical work., Methods: Using PubMed, Medline, Elsevier, and CNKI, with the following mesh words: "vancomycin", "local / intraoperative / topical / intrawound", "TJA", "TKA", "THA", "total joint arthroplasty", "total knee arthroplasty", "total hip arthroplasty", "infection", and "SSI", to search for case-control research papers on the impact of prophylactic application of vancomycin powder on the incidence of postoperative infection, we compared the overall infection rate in the literature by using RevMan 5.3 meta-analysis software and analyzed the impact of vancomycin on the infection rate of different parts and types of TJA according to different subgroups., Results: A total of 22 qualified studies were selected; twenty-five studies compared the effect of prophylactic use of vancomycin powder on infection rates after TJA. There were 23,363 cases in total, including 9545 cases in the vancomycin group and 13,818 cases in the control group. The results of the meta-analysis showed that the possibility of postoperative infection after prophylactic use of vancomycin powder was significantly lower than that without vancomycin risk ratio: 0.38 [0.23,0.59], P < 0.01). However, a meta-analysis of randomized controlled trials (RCTs) showed no significant effect of vancomycin on postoperative infection (P = 0.52)., Conclusion: Based on the retrospective studies, local prophylactic use of vancomycin powder in TJA can significantly reduce the incidence of postoperative infection. High-quality RCTs should be carried out to further evaluate these results., (© 2024. The Author(s).)

Background: Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. Omadacycline, an aminomethylcycline tetracycline, has potent in vitro activity against C difficile and a low propensity to cause CDI in clinical trials. We aimed to assess fecal pharmacokinetics and gut microbiome effects of oral omadacycline compared to oral vancomycin in healthy adults., Methods: This was a phase 1, nonblinded, randomized clinical trial conducted in healthy volunteers aged 18-40 years. Subjects received a 10-day course of omadacycline or vancomycin. Stool samples were collected at baseline, daily during therapy, and at follow-up visits. Omadacycline and vancomycin stool concentrations were assessed, and microbiome changes were compared., Results: Sixteen healthy volunteers with a mean age of 26 (standard deviation [SD], 5) years were enrolled; 62.5% were male, and participants' mean body mass index was 23.5 (SD, 4.0) kg/m2. Omadacycline was well tolerated with no safety signal differences between the 2 antibiotics. A rapid initial increase in fecal concentrations of omadacycline was observed compared to vancomycin, with maximum concentrations achieved within 48 hours. A significant difference in alpha diversity was observed following therapy in both the omadacycline and vancomycin groups (P < .05). Bacterial abundance and beta diversity analysis showed differing microbiome changes in subjects who received omadacycline versus vancomycin., Conclusions: Subjects given omadacycline had high fecal concentrations with a distinct microbiome profile compared to vancomycin., Clinical Trials Registration: NCT06030219., Competing Interests: Potential conflicts of interest. K. W. G. has received additional research grants paid to his institution from Acurx Pharmaceuticals, Seres Therapeutics, and Vendanta Biosciences and is a consultant for Ferring Pharmaceuticals. A. G. L. received research grants paid to her institution from Seres Therapeutics and is a consultant for Ferring Pharmaceuticals. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Our study emphasizes the efficacy of whole-genome sequencing (WGS) in addressing outbreaks of vancomycin-resistant enterococci. WGS enables the identification and tracking of resistant bacterial strains, early detection and management of novel infectious disease outbreaks, and the appropriate selection and use of antibiotics. Furthermore, our approach deepens our understanding of how resistant bacteria transfer genes and adapt to their environments or hosts. For modern medicine, these insights have significant implications for controlling infections and effectively managing antibiotic use in the current era, where antibiotic resistance is progressing., Competing Interests: The authors declare no conflict of interest.

Introduction: Nosocomial meningitis may occur after procedures affecting the central nervous system or following traumatic injury. The causative infectious organism is commonly Staphylococcus aureus, a Gram-positive bacterium. The aim of the present study was to compare the effectiveness of two antibacterial agents, ceftobiprole and vancomycin, in an animal model of methicillin-resistant S. aureus (MRSA) meningitis., Method: The strain of MRSA used was ATCC 43300. The animals were divided into three groups and infected intracisternally with MRSA. Controls received no antibiotherapy while the ceftobiprole group received 25 mg/kg and the vancomycin group received 20 mg/kg intravenously. Blood and cerebrospinal fluid (CSF) samples were collected at three time points. All animals were euthanized at 73 h after start of treatment., Results: There was a significant difference (p &lt; 0.05) between both treatment groups and the control animals at 24 h (drug trough) and 73 h (1 h after third dose) after start of treatment in terms of CSF bacterial levels. At 73 h, there was a significant difference in survival between the control group and the two treatment groups but no difference between the treated animal survival rates., Conclusion: Intravenous treatment with ceftobiprole and vancomycin appears to be equally effective in a rabbit model of MRSA meningitis., (© 2024 S. Karger AG, Basel.)

Aim: Vancomycin, a crucial treatment for Gram-positive bacteria, necessitates therapeutic drug monitoring (TDM) to prevent treatment failures. We investigated the healthcare professional's compliance toward TDM of vancomycin recommendations and follow-up levels. Materials & methods: We collected data from 485 patients who received vancomycin in the Children's Cancer Hospital Egypt 57357 medical records system (Cerner) over 4 months, from January to April 2020. Results: Our data shows that only 54% of patients had TDM requests from healthcare professionals for the total patients who received vancomycin treatment. The healthcare professionals' compliance with the recommendations was 91.7%, while the follow-up levels were 66.7%. Conclusion: While overall adherence to recommendations is strong, enhancing compliance with follow-up levels remains a priority for improvement.

Objectives: To estimate the generalizability of treatment effects observed in the VANCO trial to a broader population of patients with tibial plateau or pilon fractures., Methods: Design and Setting: Clinical trial data from 36 United States trauma centers and Trauma Quality Programs registry data from more than 875 Level I-III trauma centers in the United States and Canada.Patient Selection Criteria: Patients enrolled in the VANCO trial treated with intrawound vancomycin powder from January 2015 to June 2017 and 31,924 VANCO-eligible TQP patients admitted in 2019 with tibial plateau and pilon fractures.Outcome Measure and Comparisons: Deep surgical site infection and gram-positive deep surgical site infection estimated in the TQP sample weighed by the inverse probability of trial participation., Results: The 980 patients in the VANCO trial were highly representative of 31,924 TQP VANCO-eligible patients (Tipton generalizability index 0.96). It was estimated that intrawound vancomycin powder reduced the odds of deep surgical infection by odds ratio (OR) = 0.46 (95% confidence interval [CI] 0.25-0.86) and gram-positive deep surgical infection by OR = 0.39 (95% CI, 0.18-0.84) within the TQP sample of VANCO-eligible patients. For reference, the trial average treatment effects for deep surgical infection and gram-positive deep surgical infection were OR = 0.60 (95% CI, 0.37-0.98) and OR = 0.44 (95% CI, 0.23-0.80), respectively., Conclusions: This generalizability analysis found that the inferences of the VANCO trial generalize and might even underestimate the effects of intrawound vancomycin powder when observed in a wider population of patients with tibial plateau and pilon fractures., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Focus on reviewing a vigorous research effort to improve the safety profile of vancomycin powder (VP) and its optimal dose in reducing periprosthetic joint infection (PJI) is the need of the hour. This systematic review and meta-analysis attempt to explore the ongoing use of VP and VP + povidone iodine (PI) lavage to prevent PJI of hip/knee arthroplasties and highlights its challenges among the orthopedic community about the existence of the major organism and its frequency in total joint arthroplasty (TJA) patients., Methods: We searched PubMed/MEDLINE, EMBASE databases regarding the outcomes of vancomycin powder (VP) and VP + povidone iodine (PI) combination in preventing periprosthetic joint infection of hip and knee arthroplasties., Results: In 5 of 7 studies, the combination of vancomycin powder (VP) and povidone iodine (PI) lavage have shown a lower risk of periprosthetic joint infection (PJI) in acute and high-risk hip and knee arthroplasties patients, with less or without serious adverse events and readmissions; while four of seven studies using VP-only found increasing rates of PJI in primary total knee arthroplasty and partial hip replacement in elderly patients with comorbidities, and significantly causes aseptic wound complications compared to the control group., Conclusions: Intra-articular vancomycin powder (VP) and povidone iodine (PI) lavage showed a significant reduction of periprosthetic joint infection in primary and revision total joint arthroplasty. Before its widespread use in clinical settings, prospective randomized studies and, most importantly, its long-term efficacy and safety are recommended., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: The American Thoracic Society Guidelines recommend vancomycin as first line option for treatment of methicillin-resistant Staphylococcus aureus. Two studies have described the pharmacokinetics (PK) of intermittent intravenous (IV) vancomycin in adult people with cystic fibrosis (PwCF). Currently, there have not been any studies describing the PK of continuous infusion vancomycin in PwCF. Our study aimed to describe the PK of continuous infusion vancomycin in adult PwCF., Methods: Included patients were adult PwCF, who were admitted to University of Utah Hospital between May 11, 2014 and August 31, 2020, and received continuous infusion vancomycin for the treatment of an pulmonary exacerbations. The primary outcome was to describe vancomycin clearance rate (CL vanco ) and total daily dose (TDD). Secondary outcomes included rates of acute kidney injury (AKI), liver injury, and infusion-related reactions., Results: Twenty patients were included in this study. The mean CL vanco was 5.08 L/h on Day 3 and 4.58 L/h on Day 7 (p = .04), and the TDD increased from 2444 mg on Day 3 to 2556 on Day 7, although not statistically significant (p = 0.26). Zero patients experienced an AKI, two patients experienced liver injury, and no patients experienced infusion-related reactions., Conclusions: This study demonstrates that continuous infusion vancomycin PK, namely CL vanco , is similar to previously reported CL vanco for intermittent dosed IV vancomycin in adult PwCF. This study suggests that continuous infusion vancomycin is likely safe to use in adult PwCF., (© 2023 Wiley Periodicals LLC.)

Purpose of Review: We summarize evidence-based considerations regarding the use of intracameral antibiotics during cataract surgery., Recent Findings: The use of intraoperative intracameral antibiotics reduced the incidence of postcataract surgery endophthalmitis 3.5-fold, with an odds ratio ranging from 0.14 to 0.19. A survey of the American Society of Cataract and Refractive Surgery showed usage of intracameral injections of antibiotics increased by 16% in the United States between 2014 and 2021. The frequency of vancomycin usage has sharply dropped to 6%, while moxifloxacin is now the dominant choice at 83% among respondents. One analysis showed that 2500 patients need to be treated with intracameral antibiotics to prevent one case of endophthalmitis. A 500 μg intracameral moxifloxacin at $22 dollars per dose is cost-effective, including for patients with posterior capsular rupture (PCR)., Summary: Studies substantiate the safety and efficacy of intracameral antibiotics for endophthalmitis prophylaxis. Intracameral moxifloxacin and cefuroxime are the most common choices. While vancomycin shows potential for efficacy, further studies evaluating clinical outcomes are needed. Adverse events are rare and commonly due to errors in preparation. Topical antibiotics do not provide additional prophylactic benefits to intracameral regimens. Intracameral antibiotics given alone are cost-effective., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current practice guidelines favour fidaxomicin over vancomycin and exclude metronidazole from the recommended standard regimen for Clostridioides difficile infection (CDI), based on lower recurrence rates with fidaxomicin, giving little weight to mortality or the clinical implications of recurrences., Objectives: To compile the effects of metronidazole, glycopeptides (vancomycin or teicoplanin), and fidaxomicin for CDI on mortality and other patient-relevant outcomes., Data Sources: PubMed, the Cochrane Library, ClinicalTrials.gov, conference proceedings, and Google Scholar, until August 2023., Study Eligibility Criteria: Randomized controlled trials (RCTs)., Participants: Adult patients experiencing primary or recurrent CDI., Interventions: Glycopeptides versus fidaxomicin or metronidazole (comparators)., Assessment of Risk of Bias: We used the Risk of Bias 2 (RoB 2) tool for randomized trials, focusing on the outcome of all-cause mortality., Methods of Data Synthesis: Random effects meta-analyses were performed for dichotomous outcomes. Outcomes were summarized preferentially for all randomly assigned patients., Results: Thirteen trials were included. There was no significant difference in all-cause mortality (risk ratio [RR] < 1 favouring the comparator) between vancomycin and fidaxomicin (RR 0.86, 95% CI 0.64-1.14, 8 RCTs, 1951 patients) or metronidazole (RR 0.78, 95% CI 0.46-1.32, 4 RCTs, 808 patients), with low and very low certainty of evidence, respectively. No significant difference in initial treatment failure between fidaxomicin and vancomycin was found, however, initial treatment failure was higher with metronidazole (RR 1.58, 95% CI 1.10-2.27, 5 RCTs, 843 patients). No study reported on symptomatic recurrence necessitating re-treatment among all randomly assigned patients. Among initially cured patients, symptomatic recurrence necessitating re-treatment was lower with fidaxomicin than with vancomycin (RR 0.54, 95% CI 0.42-0.71, 6 RCTs, 1617 patients). None of the studies reported on other CDI complications or the burden of infection on daily activities., Conclusions: Setting patient-relevant outcomes for CDI independently of the RCT definitions and results might lead to less confidence in the guidance for CDI management., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate if inflammation score (IS), calculated from the cornea, anterior chamber, iris, and vitreous, indicates endophthalmitis severity., Methods: In a prospective study, consecutive adults with a clinical diagnosis of post-cataract endophthalmitis within 6 weeks of surgery were recruited. Patients were allocated to IS-based primary treatment (IS < 10: intravitreal injection and IS ≥ 10: vitrectomy) and randomized to two intravitreal antibiotics combinations (vancomycin + ceftazidime and vancomycin + imipenem). Undiluted vitreous microbiology work-up included culture susceptibility, polymerase chain reaction, Sanger sequencing, and targeted next-generation sequencing., Results: The average age of 175 people was 63.4 ± 10.7 years and included 52.6% small incision cataract surgery and 47.4% phacoemulsification surgery. Severe endophthalmitis (IS ≥ 20), diagnosed in 27.4% of people, had a shorter time to symptoms (average 5.4 vs 8.7 days; P = 0.018), poorer presenting vision (all ≤ hand motion), higher culture positivity (50% vs 30.7%; P = 0.032), and higher Gram-negative bacterial infection (70.8% vs 46.2%; P = 0.042). For IS ≥ 20 discriminant and Gram-negative infection, Spearman's coefficient was 0.7 [P < 0.0001, 95% confidence interval (CI) 0.59-0.82], with an area under the receiver operating characteristic curve of 0.9 (95% CI 0.85-0.94, P < 0.0001), a Youden index J of 0.74, a sensitivity of 87.2%, and a specificity of 87.5%. The final vision of >20/400 and >20/100 was regained in 50.2% and 29.1% of people, respectively. The susceptibility of common Gram-positive cocci and Gram-negative bacilli was the highest for vancomycin (95.0%) and colistin (88.6%), respectively. NGS detected polymicrobial infection in 88.5% of culture-negative endophthalmitis., Conclusions: Higher inflammation scores indicated severe disease and Gram-negative infection in post-cataract endophthalmitis., (Copyright © 2023 Copyright: © 2023 Indian Journal of Ophthalmology.)

Introduction: Monitoring of AUC24 was updated recommendation in the guideline for the therapeutic drug monitoring (TDM) of vancomycin in Chinese pharmacological society published in 2020. Vancomycin pharmacokinetic profiles are diverse and unique in critically ill patients because of the drastic variability of the patients' physiological parameters, while the study for population pharmacokinetic (PPK) models in Chinese critically ill patients has been rarely reported. The objectives of this study were to construct a PPK model to describe the pharmacokinetic characteristics of vancomycin in critically ill patients and to individualize vancomycin dosing by model-informed Bayesian estimation for maintenance of AUC24 target at 400-650 mg h/L recommended by the 2020 guideline., Methods: Vancomycin with different dosing was administered intravenously over 1 h for critically ill patients, TDM was started at 48 h or 72 h since initiation of vancomycin therapy for patients. Blood samples were collected from patients for trough concentrations or Cmax. Vancomycin concentrations were determined by high-performance liquid chromatography method with ultraviolet detection. PPK model was performed using the nonlinear mixed-effect model (NONMEM®). Individual PK parameters for critically ill patients treated with vancomycin were estimated using a post hoc empirical Bayesian method based on the final PPK model. AUC24 was calculated as the total daily dose divided by the clearance (L/h)., Results: The PPK of vancomycin was determined by a one-compartment model with creatinine clearance as fixed effects. The PK estimates in the final model generally agreed with the median estimates and were contained within the 95% CI generated from the bootstrap results, indicating good precision and stability in the final model. The visual predictive check plots showed the adequate predictive performance of the final PK model and supported a good model fit. The model-informed Bayesian estimation was used to predict the AUC24 of critically ill patient by the acquired TDM results, and the dosing adjustment by maintenance of AUC24 at 400-650 mg h/L had made a great therapeutic effect for the case., Conclusion: This study established a PPK model of vancomycin in Chinese critically ill patients, and individualized dosing of vancomycin by model-informed Bayesian estimation to maintain an AUC24 target at 400-650 mg h/L has been successfully applied in clinic. This result supports the continued use of model-informed Bayesian estimation to vancomycin treatment in critically ill patients., (© 2023 S. Karger AG, Basel.)

Purpose: The extensive use of vancomycin has led to the development of Staphylococcus aureus strains with varying degrees of resistance to vancomycin. The present study aimed to explore the molecular causes of vancomycin resistance by conducting a proteomics analysis of subcellular fractions isolated from vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-sensitive S. aureus (VSSA) strains., Methods: We conducted proteomics analysis of subcellular fractions isolated from 2 isogenic S. aureus strains: strain 11 (VSSA) and strain 11Y (VISA). We used an integrated quantitative proteomics approach assisted by bioinformatics analysis, and comprehensively investigated the proteome profile. Intensive bioinformatics analysis, including protein annotation, functional classification, functional enrichment, and functional enrichment-based cluster analysis, was used to annotate quantifiable targets., Results: We identified 128 upregulated proteins and 21 downregulated proteins in strain 11Y as compared to strain 11. The largest group of differentially expressed proteins was composed of enzymatic proteins associated with metabolic and catalytic activity, which accounted for 32.1% and 50% of the total proteins, respectively. Some proteins were indispensable parts of the regulatory networks of S. aureus that were altered with vancomycin treatment, and these proteins were related to cell wall metabolism, cell adhesion, proteolysis, and pressure response., Conclusion: Our proteomics study revealed regulatory proteins associated with vancomycin resistance in S. aureus. Some of these proteins were involved in the regulation of cell metabolism and function, which provides potential targets for the development of strategies to manage vancomycin resistance in S. aureus., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To describe a rare case of unilateral, endogenous endophthalmitis caused by Aggregatibacter aphrophilus (HACEK group) confirmed in vitreous and blood cultures, in a patient with dentophobia., Methods: Case report., Patients: A seventy-five-year-old male patient with Type 2 diabetes, previous myocardial infarction, and pacemaker implantation., Results: Patient was observed with sudden loss of vision at the Department of Ophthalmology, Uppsala University. Initial diagnosis was posterior vitreous detachment and anterior uveitis, but progression of disease led to vitrectomy, which actually demonstrated endophthalmitis and growth of A. aphrophilus of the HACEK group. Aggregatibacter bacteremia and pacemaker endocarditis were also identified and dental examination confirmed growth of Aggregatibacter in the oral cavity. Intravitreal treatment with ceftazidime and vancomycin according to Endophthalmitis Vitrectomy Study protocol was administered with quick resolution of endophthalmitis., Conclusion: Aggregatibacter endophthalmitis is a rare, but devastating cause of vision loss where immediate diagnosis may be delayed. Prompt diagnosis may be facilitated by a thorough medical history and early vitreous biopsy. Systemic investigation by an infectious disease specialist and multidisciplinary assessment are mandatory. Ophthalmologic treatment is effective with intravitreal injections of ceftazidime and vancomycin.

Initial specimen diversion devices (ISDDs) are a potential solution for reducing blood-culture contamination rates. We report the implementation of an ISDD associated with a sustained reduction in blood-culture contamination rates for >18 months after implementation. We did not observe a clinically significant reduction in inpatient vancomycin usage.

Importance: Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that is resistant to multiple drugs and can cause serious infections. In recent years, one of the most widespread strains of MRSA worldwide has been the clonal complex 5 (CC5) type. Sequence type 5 (ST5) and ST764 are two prevalent CC5 strains. Although ST5 and ST764 are genotypically identical, ST764 is classified as a hybrid variant of ST5 with characteristics of community-associated MRSA (CA-MRSA). In contrast to ST5, ST764 lacks the tst and sec genes but carries the staphylococcal enterotoxin B ( seb ) gene. Vancomycin is commonly used as the first-line treatment for MRSA infections. However, it is currently unclear whether the genetic differences between the ST5 and ST764 strains have any impact on the efficacy of vancomycin in treating MRSA infections. We conducted a prospective observational study comparing the efficacy of vancomycin against ST5-MRSA and ST764-MRSA in five hospitals in China. There were significant differences in bacteriological efficacy between the two groups, with virulence genes, such as the tst gene, being a risk factor for bacterial persistence (adjusted odds ratio, 4.509; 95% confidence interval, 1.216 to 16.724; P = 0.024). In the future, it may be necessary to consider personalized vancomycin treatment strategies based on the genetic characteristics of MRSA isolates., Competing Interests: The authors declare no conflict of interest.

Background: To determine whether there is any difference in graft rerupture rates and clinical outcomes between cases having vancomycin graft presoaking vs. no vancomycin presoaking in anterior cruciate ligament (ACL) reconstruction (ACLR)., Methods: Systematic review and meta-analysis. PubMed, Embase, CINAHL, and Cochrane CENTRAL were searched. Full published studies reporting on the relation between vancomycin graft presoaking and rates of graft rerupture and/or clinical outcomes in ACLR surgery vs. no vancomycin graft presoaking were included. Data extraction and quality appraisal were performed. Meta-analysis was conducted using a random effects model. The study's protocol was prospectively registered with PROSPERO (CRD42021290608)., Results: The literature search identified 907 records. After removing duplicates and those not meeting inclusion criteria, 8 studies were included. Meta-analysis showed that the estimated risk of hamstring graft rerupture was lower in cases presoaked with vancomycin vs. those having no presoaking (3.2% vs. 6.2% rerupture rate, risk ratio [RR] = 0.507, 95% CI, 0.39-0.737, p < 0.001). Similarly, the estimated risk of graft rerupture was lower in cases presoaked with vancomycin vs. those having no presoaking when the analysis included various ACL graft types (2.7% vs. 3.9% rerupture rate, RR = 0.557, 95% confidence interval [CI], 0.403-0.771, p < 0.001). Meta-analysis also showed that vancomycin graft presoaking was associated with similar International Knee Documentation Committee scores as compared with no presoaking when looking at hamstring grafts (estimated mean difference 0.112, 95% CI, -2.359 to 2.582, p = 0.929) or when considering various graft types (estimated mean difference 0.933, 95% CI, -0.140 to 2.006, p = 0.088)., Conclusion: Vancomycin graft presoaking is a safe practice and does not compromise ACL graft rerupture rates or clinical outcomes., Level of Evidence: Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B42)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)