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Study Design: Retrospective., Objective: Evaluate whether the use of vancomycin powder (VP) placed in the surgical site before wound closure prevents delayed deep surgical site infections (DDI)., Summary of Background Data: DDI after posterior spinal fusion (PSF) in adolescent idiopathic scoliosis (AIS) patients remains a significant and major complication. The use of VP to prevent acute surgical site infection has been reported, but the impact on DDI is unknown., Materials and Methods: AIS patients treated over the past 20 years with PSF or instrumentation from a large multicenter registry were reviewed. Patients were divided into two groups: intraoperative vancomycin powder placed in the wound (VP) or no antibiotics placed in the wound (NVP). DDI was defined as an infection that occurred >90 days after surgery and required surgical intervention in the operating room. Patients who developed a DDI had secondary verification of VP use or not. χ 2 and Kaplan-Meier (K-M) survivorship analyses were used to compare demographics and the incident rate of DDI between groups., Results: Totally, 4145 cases met the inclusion criteria for this study. A total of 43 DDI cases were identified (1.0%). The incidence of DDI for the VP group was 0.2% (4/2111), and 1.9% (39/2034) in the NVP group ( P <0.001). Given the difference in follow-up for the two groups, a cumulative survival and Kaplan-Meier analysis revealed the VP group had significantly better "survival" (no DDI) than the NVP group ( P <0.001)., Conclusion: DDIs are significant adverse events that can greatly complicate patient recovery after PSF for AIS, including rehospitalization. This study found that patients who received VP intraoperatively were 10 times less likely to develop a DDI than those who did not receive VP. Although other advances and changes in surgical techniques may contribute to the significant decrease in infections found in the more recent VP cohort, VP should be considered as a prophylactic measure., Level of Evidence: 4., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Retrospective cohort., Objective: The purpose of this study was to compare the efficacy of cefazolin versus vancomycin for perioperative infection prophylaxis., Summary of Background Data: The relative efficacy of cefazolin alternatives for perioperative infection prophylaxis is poorly understood., Materials and Methods: This study was a single-center multisurgeon retrospective review of all patients undergoing primary spine surgery from an institutional registry. Postoperative infection was defined by the combination of three criteria: irrigation and debridement within 3 months of the index procedure, clinical suspicion for infection, and positive intraoperative cultures. Microbiology records for all infections were reviewed to assess the infectious organism and organism susceptibilities. Univariate and multivariate analyses were performed., Results: A total of 10,122 patients met inclusion criteria. The overall incidence of infection was 0.78%, with an incidence of 0.73% in patients who received cefazolin and 2.03% in patients who received vancomycin (OR: 2.83, 95% CI: 1.35-5.91, P= 0.004). Use of IV vancomycin (OR: 2.83, 95% CI: 1.35-5.91, P =0.006), BMI (MD: 1.56, 95% CI: 0.32-2.79, P =0.014), presence of a fusion (OR: 1.62, 95% CI: 1.04-2.52, P =0.033), and operative time (MD: 42.04, 95% CI: 16.88-67.21, P =0.001) were significant risk factors in the univariate analysis. In the multivariate analysis, only noncefazolin antibiotics (OR: 2.48, 95% CI: 1.18-5.22, P =0.017) and BMI (MD: 1.56, 95% CI: 0.32-2.79, P =0.026) remained significant independent risk factors. Neither IV antibiotic regimen nor topical vancomycin significantly impacted Gram type, organism type, or antibiotic resistance ( P >0.05). The most common reason for antibiosis with vancomycin was a penicillin allergy (75.0%)., Conclusions: Prophylactic antibiosis with IV vancomycin leads to a 2.5 times higher risk of infection compared with IV cefazolin in primary spine surgery. We recommend the routine use of IV cefazolin for infection prophylaxis, and caution against the elective use of alternative regimens like IV vancomycin unless clinically warranted., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Infection is a common mode of failure in lower extremity endoprostheses. The Prophylactic Antibiotic Regimens in Tumor Surgery trial reported that 5 days of cefazolin had no difference in surgical site infection compared with 24 hours of cefazolin. Our purpose was to evaluate infection rates of patients receiving perioperative cefazolin monotherapy, cefazolin-vancomycin dual therapy, or alternative antibiotic regimens., Methods: A single-center retrospective review was conducted on patients who received lower extremity endoprostheses from 2008 to 2021 with minimum 1-year follow-up. Three prophylactic antibiotic regimen groups were compared: cefazolin monotherapy, cefazolin-vancomycin dual therapy, and alternative regimens. The primary outcome was deep infection, defined by a sinus tract, positive culture, or clinical diagnosis. Secondary outcomes were revision surgery, microorganisms isolated, and superficial wound issues., Results: The overall deep infection rate was 10% (30/294) at the median final follow-up of 3.0 years (IQR 1.7 to 5.4). The deep infection rates in the cefazolin, cefazolin-vancomycin, and alternative regimen groups were 8% (6/72), 10% (18/179), and 14% (6/43), respectively ( P = 0.625). Patients not receiving cefazolin had an 18% deep infection rate (6/34) and 21% revision surgery rate (7/34) compared with a 9% deep infection rate (24/260) ( P = 0.13) and 12% revision surgery rate (31/260) ( P = 0.17) in patients receiving cefazolin. In those not receiving cefazolin, 88% (30/34) were due to a documented penicillin allergy, only two being anaphylaxis. All six patients in the alternative regimen group who developed deep infections did not receive cefazolin secondary to nonanaphylactic penicillin allergy., Conclusion: The addition of perioperative vancomycin to cefazolin in lower extremity endoprosthetic reconstructions was not associated with a lower deep infection rate. Patients who did not receive cefazolin trended toward higher rates of deep infection and revision surgery, although not statistically significant. The most common reason for not receiving cefazolin was a nonanaphylactic penicillin allergy, highlighting the continued practice of foregoing cefazolin unnecessarily., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

This study was designed to investigate the effectiveness, safety, and cost-effectiveness of norvancomycin in the management of acute hematogenous osteomyelitis in pediatric patients. We conducted a retrospective study on cases of osteomyelitis in pediatric patients treated with norvancomycin or vancomycin at Hebei Children's Hospital from January 2015 to February 2023. The patients were categorized into the norvancomycin group and the vancomycin group. Clinical data regarding efficacy, safety, and cost-effectiveness before and after drug treatment were collected for comparative analysis. Each group contained 104 children. After 14 days of treatment, there were no statistically significant differences in the incidence of adverse events and efficacy indexes between the 2 groups. However, the total hospitalization cost of the norvancomycin group (¥28765.35 ± ¥11835.98) was significantly lower than that of the vancomycin group (¥43776.06 ± ¥33365.30) (P = .000). Additionally, compared to the vancomycin group, both the clinical efficacy cost ratio (290.44 vs 437.76) and bacteriological clearance cost ratio (356.14 vs 576.30) were lower in the norvancomycin group. Norvancomycin demonstrates comparable efficacy to the first-line drug vancomycin in treating acute hematogenous osteomyelitis in pediatric patients. Moreover, norvancomycin can significantly mitigate treatment expenses and exhibit favorable cost-effectiveness., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) after initial infection in patients with Clostridioides difficile from a German multicentre cohort study., Methods: The IBIS multicentre cohort enrolled patients with an index episode of C. difficile infection between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within 10 days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections., Results: Of the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within 10 days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event free. The Cox proportional hazards model revealed differences in EFS for the overall population and both subgroups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% CI, 0.33-0.65]; non-severe: HR 0.39; [95% CI, 0.24-0.60]; severe: HR 0.52; [95% CI, 0.28-0.95])., Discussion: Our analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared with metronidazole across all severity levels., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The role of combination therapies for serious methicillin-resistant Staphylococcus aureus (MRSA) infections is widely debated., Methods: This retrospective cohort study included adults with MRSA bacteraemia treated between January 1, 2013, to December 31, 2022. Patients receiving combination therapy with vancomycin and ceftaroline were matched in a 2:1 ratio with those on vancomycin monotherapy based on bacteraemia source and illness severity. The primary outcome was frequency of bacteraemia recurrence. Secondary outcomes were all cause 30/90-day mortality, recurrence or mortality at 30/90 days and in hospital length of stay., Results: Of 57 patients included, 37 (65%) were in the combination group. The overall intensive care unit admission rate was 63.2% (36/57) and the Pitt Bacteraemia Score was 1 [0-4] at the time of diagnosis. The most common source of infection was endovascular/endocarditis (n = 36, 63.2%). Demographic and clinical characteristics were similar between the monotherapy and combination group of patients, except for higher body mass index (32.5 [25.5-36.4] vs. 24.4 [20.9-29], p = 0.004) and a greater immunosuppression prevalence (3 (15%) vs. 0 (0%), p = 0.039) in monotherapy group. There was no significant difference in bacteraemia recurrence (3 (15%) vs. 4 (10.8%), p = 0.7) or all-cause 30-day mortality (3 (15%) vs. 4 (10.8%), p = 0.7) between the two groups., Conclusion: The results of this study are limited by a retrospective observational design; however, combination of vancomycin and ceftaroline for MRSA bacteraemia was not associated with lower bacteraemia recurrence or mortality compared to vancomycin monotherapy., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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., (© Journal of the Association of Physicians of India 2024.)

Objectives: Infections represent a major risk for critically ill neonatal and paediatric patients requiring extracorporeal life-saving support such as extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapies (CRRT). Patient outcomes rely on achieving target antimicrobial concentrations. In critically ill adults on extracorporeal support, suboptimal antimicrobial concentrations have been shown to be common. Our objective was to systematically review antimicrobial pharmacokinetic studies in critically ill term neonatal and paediatric patients receiving ECMO and/or CRRT and compare them to similar cohorts of patients not receiving ECMO or CRRT., Methods: Studies published between 1990 and 2022 were identified through systematic searches in PUBMED, Embase, Web of Science, Medline, Google Scholar and CINAHL. Studies were included which provided antimicrobial pharmacokinetic parameters (volume of distribution and clearance) in the neonatal and paediatric patients receiving ECMO and/or CRRT. Studies were excluded if no antimicrobial pharmacokinetic parameters were described or could be calculated., Results: Forty-four pharmacokinetic studies were identified describing 737 patients, with neonatal patients recruited in 70% of the ECMO studies and <1% of the CRRT studies. Of all the studies, 50% were case reports or case series. The pharmacokinetics were altered for gentamicin, daptomycin, ceftolozane, micafungin, voriconazole, cefepime, fluconazole, piperacillin, and vancomycin, although considerable patient variability was described., Conclusion: Significant gaps remain in our understanding of the pharmacokinetic alterations in neonatal and paediatric patients receiving ECMO and CRRT support., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Decision-making in clinical medicine ideally is based upon evidence from randomized, placebo-controlled trials (RCTs) and subsequent systematic reviews and meta-analyses. However, for orphan diseases, the expectation of having one or multiple RCTs that inform clinical guidelines or justify specific treatments can be unrealistic and subsequent therapeutic nihilism can be detrimental to patients. This article discusses the benefits of therapeutic decision-making in the context of orphan diseases, focusing on primary sclerosing cholangitis (PSC) as an example of an orphan disease with poor clinical outcomes. PSC is a rare disorder characterized by inflammation and progressive fibrosis of the bile ducts. It carries a high risk of liver failure, malignancies, and debilitating symptoms that impair quality of life. Liver transplantation is currently the only life-prolonging intervention for PSC, but it is not a curative option. The article highlights the potential benefits of treating PSC patients with oral vancomycin (OV), which has shown significant clinical responses and improved quality of life in some cases. However, access to OV therapy is limited due to the lack of RCTs supporting its use. The standard requirement of having evidence from RCTs may result in withholding potentially life-altering and/or life-saving treatments for patients with orphan diseases. Conducting RCTs is challenging in these patient populations due to difficulties in recruiting the required patient cohorts and limited commercial returns. A standardized 'adaptive treatment strategy' is proposed to address this. This approach leverages the best available evidence for specific treatments, considers individual clinical responses, and adjusts treatment over time., (© 2024. The Author(s).)

Objectives: To estimate risk factors for acute kidney injury (AKI) and the effect of AKI on mortality in Staphylococcus aureus bacteraemia, while taking into account recurrent AKI episodes, competing risks, time-varying variables, and time-varying effects., Methods: We performed an unplanned analysis using data from a multicentre cohort study of patients with Staphylococcus aureus bacteraemia (SAB). The primary outcome was cumulative incidence of AKI, according to Kidney Disease Improving Global Outcomes definitions., Results: We included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (hazard ratio (HR) 1.013, 95% CI 1.001-1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01-1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28-2.42), septic shock (HR 3.28, 95% CI 2.31-4.66), persistent bacteraemia (HR 1.53, 95% CI 1.08-2.17), and vancomycin therapy (HR 1.80, 95% CI 1.05-3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin, and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91-6.23)., Discussion: The incidence of AKI in SAB is high and a substantial proportion of patients develop recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. The clinical outcome of patients with SAB complicated by AKI is worse than previously estimated., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This study was conducted to evaluate the cost-benefit indicators of a vancomycin monitoring protocol based on area under the curve estimation using commercial Bayesian software., Methods: This quasi-experimental study included patients who were aged >18 years with a vancomycin prescription for >24 hours. Patients who were terminally ill or those with acute kidney injury (AKI) ≤24 hours were excluded. During the preintervention period, doses were adjusted based on the trough concentration target of 15-20 mg/L, whereas the postintervention period target was 400-500 mg × h/L for the area under the curve. The medical team was responsible for deciding to stop the antimicrobial prescription without influence from the therapeutic drug monitoring team. The main outcomes were the incidence of AKI and length of stay. Cost-benefit simulation was performed after statistical analysis., Results: There were 96 patients in the preintervention group and 110 in the postintervention group. The AKI rate decreased from 20% (n = 19) to 6% (n = 6; P = 0.003), whereas the number of vancomycin serum samples decreased from 5 (interquartile range: 2-7) to 2 (interquartile range: 1-3) examinations per patient ( P < 0.001). The mean length of hospital stay for patients was 26.19 days after vancomycin prescription, compared with 17.13 days for those without AKI ( P = 0.003). At our institution, the decrease in AKI rate and reduced length of stay boosted yearly savings of up to US$ 369,000 for 300 patients receiving vancomycin therapy., Conclusions: Even in resource-limited settings, a commercial Bayesian forecasting-based protocol for vancomycin is important for determining cost-benefit outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Estimating the serum vancomycin (VCM) concentrations of lean and patients with obesity is challenging. Additionally, VCM dosing for Japanese patients undergoing hemodialysis remains particularly unclear. This study aimed to determine the impact of the physical build on serum VCM concentrations of Japanese patients undergoing hemodialysis., Methods: This retrospective cohort study included hospitalized patients undergoing hemodialysis, who received treatment with VCM between May 1, 2019, and December 31, 2021, at Kansai Rosai Hospital, which is a 642-bed acute care hospital in Japan. Patients were divided into the following three groups based on their body mass index (BMI): lean group (≤18.5 kg/m 2 ), normal group (18.5-25 kg/m 2 ), and obese group (≥25 kg/m 2 ). The VCM dose and predialysis serum VCM concentration (PVC) were compared., Results: This study included 191 patients. There were 50 patients in the lean group, 85 in the normal group, and 56 in the obese group. The median loading doses per body weight were 24.0, 22.1, and 21.2 mg/kg for the lean, normal, and obese groups, respectively. The VCM dose per body weight decreased significantly with increasing BMI. The median PVCs of the lean and normal groups were approximately 15 mg/L (not significantly different). However, the median PVC of the obese group was 18.3 mg/L, which was significantly higher (P < 0.001)., Conclusions: The VCM dose per body weight for Japanese patients undergoing hemodialysis should be adjusted based on the BMI., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe drug-induced hypersensitivity reaction with 10% mortality. To date, there is insufficient evidence regarding the association between DRESS/DIHS and serum levels of vancomycin (VCM). Here, we report the case of a 46-year-old woman undergoing peritoneal dialysis who developed VCM-induced DRESS/DIHS. She was hospitalized for peritonitis with abdominal pain and treated with VCM. On day 10 of hospitalization, her abdominal symptoms improved; however, fever, skin rash, lymphadenopathy, eosinophilia, atypical lymphocytes, and liver and renal dysfunction developed. Based on the clinical course and laboratory findings, we diagnosed the patient with DRESS/DIHS due to VCM. Since her serum VCM concentration was high at 39.8 μg/mL, hemodialysis (HD) was performed to remove VCM, which caused her symptoms to improve. However, serum levels of VCM rebounded and the same symptoms recurred. Therefore, we re-performed HD; no further relapse occurred. This clinical course showed that increased serum VCM levels were associated with DRESS/DIHS onset and severity, suggesting that it is a blood level-dependent disease and that removal of VCM by HD is a potential therapeutic option., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Lower gastrointestinal perforation (LGP) is a surgical emergency disease that can result in secondary bacterial peritonitis. Microbiological studies on LGP are rare. The present study aimed to ascertain the microbiological profile of LGP in patients admitted to the intensive care unit (ICU) at our institute after surgery. In addition, we investigated whether initial empirical therapy with vancomycin was associated with in-hospital mortality, duration of ICU stay, and duration of ventilator support., Methods: This single-center, retrospective, observational study was conducted at Kobe City Medical Center General Hospital, Japan. The study population included all patients diagnosed with LGP who were admitted to the ICU after emergency surgery between 2017 and 2023. The primary outcome assessed was the microbiological profile of microorganisms isolated from ascites fluid and blood of the participants. The secondary end-points were in-hospital mortality, duration of ICU stay, and duration of ventilator support. We performed univariate and multivariate regression analyses to evaluate the end-points., Results: During the study period, 89 patients were included in the analysis. The most commonly identified pathogen from the ascites cultures was Escherichia coli (65.2%), followed by Enterococcus spp. (51.7%). E. faecium was identified in 16 (18.0%) ascites samples. The microbiological profile of critically ill patients with LGP admitted to the ICU after surgery was similar to that of previous studies on intra-abdominal infection (IAI). Therefore, the initial empirical therapy in the IAI guidelines is more appropriate for LGP. Multivariate regression analysis suggested that the combination of initial empirical therapy with vancomycin was not associated with in-hospital mortality (odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.23-3.00, p = 0.955), duration of ICU stay (coefficient=-0.92, 95% CI -3.04-1.21, p = 0.393), or duration of ventilator-support (coefficient=-9.03, 95%CI -49.69-31.63, p = 0.659)., Conclusion: The microbiological profile of critically ill patients with LGP admitted to the ICU after surgery was similar to that of previous studies on IAI. However, the frequency of E. faecium in the present study was higher than that in previous studies. Initial empirical therapy with drugs such as meropenem in combination with vancomycin for E. faecium was not associated with in-hospital mortality, duration of ICU stay, and duration of ventilator support, after adjusting for confounding factors., (© 2024. The Author(s).)

Introduction: Different initial manifestations of peritoneal dialysis-associated peritonitis (PDAP) may depend on the type of pathogenic organism. We investigated the association between the clinical characteristics of PDAP and susceptibility to vancomycin and investigated the possibility of using vancomycin monotherapy alone as an initial treatment regimen for some PDAP patients to avoid unnecessary antibiotic exposure and secondary infection., Methods: Patients with culture-positive PDAP were retrospectively analyzed and divided into two groups: peritonitis with only cloudy effluent (PDAP-cloudy) or with cloudy effluent, abdominal pain and/or fever (PDAP-multi). The bacterial culture of PD effluent and antibiotic sensitivity test results were compared between groups. Logistic regression was used to investigate factors predicting susceptibility to vancomycin., Results: Of 162 episodes of peritonitis which had a positive bacterial culture of PD fluid, 30 peritonitis were in the PDAP-cloudy group, and 132 peritonitis were in the PDAP-multi group. Thirty (100%) peritonitis in the PDAP-cloudy group had gram-positive bacterial infections, which was significantly greater than that in the PDAP-multi group (51.5%) (P < 0.001). Twenty-nine (96.7%) peritonitis in the PDAP-cloudy group were susceptible to vancomycin, compared to 67 (50.8%) in the PDAP-multi group (P < 0.001). The specificity of PDAP-cloudy for vancomycin-sensitive peritonitis was 98.48%. Only one patient (3.3%) in the PDAP-cloudy group experienced vancomycin-resistant peritonitis caused by Enterococcus gallinarum, which could neither be covered by vancomycin nor by the initial antibiotic regimen recommended by the current ISPD guidelines. The presence of only cloudy effluent was an independent predictor of susceptibility to vancomycin according to multivariate analysis (OR = 27.678, 95% CI 3.191-240.103, p = 0.003), in addition to PD effluent WBC counts (OR = 0.988, 95% CI 0.980-0.996, p = 0.004), diabetes mellitus (OR = 3.646, 95% CI 1.580-8.416, p = 0.002), first episode peritonitis (OR = 0.447, 95% CI 0.207-0.962, p = 0.039) and residual renal creatinine clearance (OR = 0.956, 95% CI 0.918-0.995, p = 0.027). Addition of these characteristics increased the AUC to 0.813 (95% CI 0.0.749-0.878, P < 0.001). The specificity of presenting with only cloudy effluent for vancomycin-sensitive peritonitis was 98.48%., Conclusions: Cloudy dialysate, as the only symptom at PDAP onset, was an independent predictor of vancomycin-sensitive PDAP, which is an important new insight that may guide the choice of initial antibiotic treatment., (© 2024. The Author(s).)

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 ± 22.37) mmH2O and (9.86 ± 1.62) days, the observation subgroup were (125.43 ± 18.5) mmH2O and (7.35 ± 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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Japanese guidelines recommend metronidazole (MNZ) and vancomycin (VCM) for non-severe and severe cases of Clostridioides difficile infection (CDI), respectively. In the present study, we investigated the use of CDI antimicrobials and evaluated their clinical efficacy and validity using four severity classifications. A retrospective chart review was conducted using the data of 137 inpatients with initially positive C. difficile toxin test results and the initiation of CDI antimicrobials between April 2015 and March 2019. Patients treated with VCM or oral MNZ were included for clinical efficacy analysis of CDI antimicrobials and validation of severity classifications. The endpoints were CDI recurrence, 30-day mortality, and diarrhea cure rates. No significant differences were found between the VCM and oral MNZ groups in the CDI recurrence rate (10.4% vs. 12.7%, P = 0.707), 30-day mortality rate (12.5% vs. 5.6%, P = 0.162), and diarrhea cure rate (61.9% vs. 72.7%, P = 0.238), regardless of severity. Treatment with oral MNZ for non-severe cases was promising, confirming its usefulness according to Japanese guidelines. Further investigation of the clinical efficacy of oral MNZ in patients with first-episode CDI and evaluation of the preferred severity classification are warranted.

Introduction: Hypernatremia is a common problem among patients with severe burn injuries and seems to be associated with an unfavorable clinical outcome. The current study was designed to evaluate the impact of antibiotics with a high proportion of sodium on this phenomenon., Methods: All admissions to our burn center from 01/2017 till 06/2023 were retrospectively screened. All patients aged >18 years which suffered from at least 20 % total body surface burned area (TBSA) 2nd degree burn injuries or more than 10 % TBSA when including areas of 3rd degree burn injuries were included. The course of the serum Na-level was analyzed from two days before till two days after the start of the antibiotic treatment. Ampicillin/sulbactam, cefazoline and piperacillin/tazobactam were classified as high-dose sodium antibiotics (HPS), meropenem and vancomycin as low-dose sodium antibiotics (LPS)., Results: 120 patients met the inclusion criteria. A significant increase of the serum Na was detectable in the HPS group on day 1 and 2 after initiating the antibiotic treatment (n = 64, day 1: 2,1 (SD 4,18) mmol/l, p < 0,001; day 2: 2,44 (SD 5,26) mmol/l, p < 0,001) while no significant changes were detectable in the LPS group (n = 21, day 1: 0,18 (SD 7,45) mmol/l, p = 0,91; day 2: -0,27 (SD 7,44) mmol/l, p = 0,87). This effect was further aggravated when analyzing only the HPS patients with a TBSA ≥30 % (n = 33; day 1: 2,93 (SD 4,68) mmol/l, p = 0,002; day 2: 3,41 (SD 5,9) mmol/l, p = 0,003)., Conclusion: The amount of sodium in antibiotics seems to have a relevant impact on the serum Na during the early stages of severe burn injury. Therefore, this aspect should be taken into account when searching for the most appropriate antibiotic treatment for patients with severe burn injury, especially when being at acute risk for a clinical relevant hypernatremia., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The development of new biological agents and small molecules has revolutionized the treatment of Inflammatory Bowel Disease (IBD). However, many patients do not respond or gradually lose their response, necessitating the search for other therapeutic strategies (1). In this clinical case, we describe the evolution of a patient with difficult-to-manage Crohn's Disease (CD) who was treated with oral vancomycin.

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., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: N.B. has received consulting fees and royalties from Move up. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Objectives: This study conducted a network meta-analysis comparing linezolid, teicoplanin, daptomycin, tigecycline, and ceftaroline fosamil with vancomycin for treating MRSA-related diseases, addressing the lack of comprehensive evaluations in existing research on antibiotic therapy for MRSA infections., Methods: We systematically searched databases including PubMed, Embase, Web of Science, the Cochrane Librar up to August 22, 2023. All eligible randomized controlled trials of the six antibiotics were included in the NMA, and their effectiveness and safety were compared across various MRSA-related diseases. Categorical data were used for the odds ratio (OR), and continuous data were used for mean difference (SMD). The surface under the cumulative ranking (SUCRA) was employed to evaluate the incidence rate., Results: According to SUCRA results, daptomycin was the most effective treatment (73.0%) in bloodstream infections. In pulmonary infections and skin and soft tissue infections, linezolid out-performed other antibiotics in effectiveness rate (90.6% and 86.3%), microbial killing rate (93.3% and 93.1%). Vancomycin showed lower adverse reactions than teicoplanin, with less hepatotoxicity compared to linezolid and tigecycline. Linezolid had higher thrombocytopenia risk but lower nephrotoxicity risk than others. Vancomycin was less effective in microbial killing rates than linezolid across various infections., Conclusion: The present research suggests that in pulmonary infections and skin and soft tissue infections, linezolid may be a better option for treating MRSA-related diseases. However, caution is warranted due to the association of linezolid with thrombocytopenia., Trial Registration: Our study protocol was registered with the International Prospective Register of SystematicReviews (PROSPERO); Registration number: CRD42024535142., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Goals: To assess fecal microbiota, live-jslm (REBYOTA, abbreviated as RBL, formerly RBX2660) efficacy and safety in participants grouped by recurrent Clostridioides difficile infection (rCDI) risk factors and treatment-related variables., Background: RBL is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration for the prevention of rCDI in adults after antibiotic treatment for rCDI., Study: Treatment success rates across subgroups for PUNCH CD3 (NCT03244644) were estimated using a Bayesian hierarchical model, borrowing data from PUNCH CD2 (NCT02299570). Treatment-emergent adverse events were summarized for the double-blind treatment period within 8 weeks., Results: Treatment differences between RBL and placebo at 8 weeks were similar to the total population for most subgroups. Treatment effect sizes were similar between CDI tests, higher for oral vancomycin courses >14 days versus ≤14 days and higher for antibiotic washout periods of 3 days versus ≤2 days. The largest reductions in the rate of rCDI with RBL versus placebo were observed for participants with a 3-day CDI antibiotic washout period and participants with ≥4 previous CDI episodes. Most RBL-treated participants experienced TEAEs that were mild or moderate in severity and related to preexisting conditions., Conclusion: This analysis provides further evidence of RBL efficacy and safety across subgroups, including those at high risk for rCDI., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis., Methods: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019., Results: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis., Conclusion: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents., Competing Interests: Declaration of Competing interest Tokimatsu I. received scholarship donations from Shionogi Pharmaceuticals, Inc. and Daiichi Sankyo Co. Ltd. Ukimura A. received scholarship donations from Shionogi Pharmaceuticals, Inc. Hiroshige Mikamo received speaker honoraria from MSD K.K., FUJIFILM Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Shionogi & Co., Ltd. Japan, Kowa Co. Ltd., Gilead Sciences K.K., GSK Group of Companies, Saraya Co. Ltd., Tsumura & Co. Japan, Nippon Becton Dickinson Company, Ltd., and FUKOKU Co., Ltd., grant supports from Asai Kasei Pharma Co., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., and FUKOKU Co., Ltd. Mitsutake K, Shinya N, Seki M, Ohara T, Uemura K, Fukunaga M, Sakai J, Nagao M, Sata M, Hamada Y, Kawasuji H, Yamamoto Y, Nakamatsu M, Koizumi Y, Aoyagi T, Sawai T, Tanaka T, Izumikawa K, Takayama Y, Nakamura K, Kanemitsu K, Nakajima K, and Akine D have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

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., (© 2024. The Author(s).)

Objectives: The trough concentration of vancomycin and the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio are crucial in determining vancomycin efficacy against methicillin-resistant Staphylococcus aureus . However, the use of similar pharmacokinetic principles in determining antibiotic efficacy against other gram-positive cocci is lacking. We performed a pharmacokinetic/pharmacodynamic analysis (association of target trough concentration values and AUC/MIC with therapeutic outcome) of vancomycin in patients with Enterococcus faecium bacteraemia., Methods: Between January 2014 and December 2021 we performed a retrospective cohort study of patients with E. faecium bacteraemia treated with vancomycin. Patients who received renal replacement therapy or had chronic kidney disease were excluded. Clinical failure, the primary outcome, was defined as a composite of 30-day all-cause mortality, vancomycin-susceptible infection requiring change of treatment, and/or recurrence. AUC 24 was estimated using a Bayesian estimation approach based on an individual vancomycin trough concentration. The MIC for vancomycin was determined using a standardised agar dilution method. Additionally, classification was used to identify the vancomycin AUC 24 /MIC ratio associated with clinical failure., Results: Of the 151 patients identified, 69 were enrolled. All MICs of vancomycin for E. faecium were ≤1.0 µg/mL. The AUC 24 and AUC 24 /MIC ratio were not significantly different between the clinical failure group and the clinical success group (432±123 µg/mL/hour vs 488±92 µg/mL/hour; p=0.075). However, 7 of 12 patients (58.3%) in the clinical failure group and 49 of 57 patients (86.0%) in the clinical success group had a vancomycin AUC 24 /MIC ratio ≥389 (p=0.041). No significant association between trough concentration or AUC 24 ≥600 µg/mL×hour and acute kidney injury was observed (p=0.365 and p=0.487, respectively)., Conclusion: The AUC 24 /MIC ratio is associated with the clinical outcome of vancomycin administration in E. faecium bacteraemia. In Japan, where vancomycin-resistant enterococcal infection is rare, empirical therapy with a target AUC 24 ≥389 should be recommended., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Enterococcus gallinarum (EG) is typically found in the gastrointestinal tracts of birds and mammals. Although its strains are rarely isolated from clinical specimens, EG can lead to septicemia in immunocompromised individuals. EG infections are uncommon in household settings, but their incidence has been rising due to increased antibiotic usage and invasive treatments, particularly in Neonatal Intensive Care Units (NICUs). EG inherently exhibits resistance to vancomycin but is highly sensitive to linezolid. Despite showing in vitro resistance, vancomycin has shown clinical efficacy in treating EG meningitis., Case Presentation: A neonate born at 30 + 2 weeks gestation was admitted to the Neonatal Intensive Care Unit (NICU) after EG was detected in blood and cerebrospinal fluid cultures. Susceptibility testing indicated that the bacterial strain was resistant to vancomycin and sensitive to linezolid. Initially, vancomycin was selected for treatment. However, due to persistent EG cultures in the blood and cerebrospinal fluid, the treatment was adjusted to linezolid. This led to a rapid decrease in platelet (PLT) count, suspected to be an adverse reaction. Concurrently, the patient experienced recurrent fever and elevated inflammatory marker levels, prompting the discontinuation of linezolid and a return to vancomycin. Subsequent administration of vancomycin stabilized the patient's condition, as evidenced by improved C-reactive protein (CRP), procalcitonin (PCT), and cerebrospinal fluid parameters, ultimately leading to discharge after an eight-week treatment period., Conclusion: This retrospective analysis highlights the efficacy of vancomycin in treating EG infections, suggesting that specific genetic phenotypes may influence treatment sensitivity. Monitoring vancomycin blood levels is crucial for determining treatment effectiveness., (© 2024. The Author(s).)

Purpose: To compare the efficacy, recurrence rate, adverse event rate and mortality of fidaxomicin compared with vancomycin in treating different types of Clostridium difficile infection (CDI)., Methods: A systematic search was conducted on PubMed, Embase, Web of Science, Cochrane Library and clinical trial registration databases for research on fidaxomicin versus vancomycin in the treatment of CDI and the retrieval period extended from the establishment of the database to July 22, 2022. A total of 15 studies were included, including 8 RCTs and 7 retrospective cohort studies., Results: Results showed that there was no significant difference in the overall efficacy of the treatment between fidaxomicin and vancomycin, and results in the subgroups of CDI hypervirulent strains and recurrent CDI were obtained, but vancomycin was more effective than fidaxomicin in the treatment of severe CDI (RR = 0.94, 95% CI: 0.90-0.98, P < .01). Results showed that fidaxomicin is superior to vancomycin in terms of 40-day recurrence rate (RR = 0.52, 95% CI: 0.38-0.70, P < .01), 60-day recurrence rate (RR = 0.38, 95% CI: 0.21-0.69, P < .01) and 90-day recurrence rate (RR = 0.62, 95% CI: 0.50-0.77, P < .01). For the recurrence rate of the treatment in CDI hypervirulent strains, severe CDI and recurrent CDI, there was no significant difference between the 2 groups. In addition, there was no significant difference in the incidence of clinical adverse reactions, and same outcomes appeared in all-cause mortality at 40-day, severe CDI and recurrent CDI, but fidaxomicin was superior to vancomycin in all-cause mortality over 60-day (RR = 0.57, 95% CI: 0.34-0.96, P = .03)., Conclusion: There were no significant differences between fidaxomicin and vancomycin in the treatment of CDI in therapeutic effectiveness and adverse reactions, while fidaxomicin was superior to vancomycin in terms of recurrence rate and long-term mortality, and vancomycin is more effective in treating severe CDI., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives : The predicted serum concentrations of vancomycin are determined using population pharmacokinetic parameters. However, the accuracy of predicting vancomycin serum concentrations in the older population remains unclear. Therefore, this study aimed to investigate the accuracy of predicting vancomycin serum concentrations and identifying elements that diminish the prediction accuracy in older people. Materials and Methods : A total of 144 patients aged 75 years or older were included. The serum vancomycin concentrations in the patients were predicted based on population pharmacokinetic parameters common in Japan. We examined the accuracy of serum vancomycin concentration prediction in elderly individuals by comparing the predicted and measured serum vancomycin concentrations in each patient. The prediction accuracy was evaluated using the mean prediction error (ME) and mean absolute error of prediction (MAE) calculated from the measured and predicted serum vancomycin concentrations in each patient. Results : The ME for all patients was 0.27, and the 95% CI included 0, indicating that the predicted values were not significantly biased compared to the measured values. However, the predicted serum concentrations in the <50 kg body weight and serum creatinine (Scr) < 0.6 mg/dL groups were significantly biased compared to the measured values. The group with a history of intensive care unit (ICU) admission showed the largest values for the ME and MAE. Conclusions : Our prediction accuracy was satisfactory but tended to be lower in underweight patients, those with low creatinine levels, and patients admitted to the ICU. Patients with multiple of these factors may experience a greater degree of decreased predictive accuracy.

The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older ( P < 0.001) and more frequently had solid cancer ( P = 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent ( P < 0.001) in the vancomycin treatment success group. The Charlson comorbidity index ( P = 0.01) and Acute Physiology and Chronic Health Evaluation II scores ( P < 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.IMPORTANCEIn this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated Staphylococcus aureus (hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia., Competing Interests: The authors declare no conflict of interest.

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

This study was condcuted to examine the association of area under the curve (AUC)/minimum inhibitory concentration (MIC) and trough concentration (C trough ) of vancomycin with treatment outcome and nephrotoxicity in infections caused by Enterococcus spp. and coagulase-negative Staphylococci (CoNS). Peak and trough concentrations were used to calculate AUC in 89 patients receiving vancomycin for infections with Enterococcus spp. (n = 65) or CoNS (n = 24). Correlations between C trough , AUC/MIC, early clinical response (ECR), and nephrotoxicity were assessed and cutoff values were determined. Sixty-three (70.8%) patients showed improvement in ECR and 10 (11.2%) experienced nephrotoxicity. Enterococcus spp. infections displayed correlations between AUC/MIC and ECR for AUC 0-24 h /MIC (r 2 = 0.27, P ≤ .05) and AUC 24-48 h /MIC (r 2 = 0.28, P ≤ .05), but not for C trough (r 2 = 0.21, P > .05). There were no correlations between C trough (r 2 = 0.26, P > .05), AUC 0-24 h /MIC (r 2 = -0.12, P > .05), AUC 24-48 h /MIC (r 2 = 0.01, P > .05) and ECR for CoNS. In the CoNS group, a moderate correlation was found between ECR and C trough at a cutoff value of 6.9 μg/mL. In addition, nephrotoxicity is also moderately associated with AUC 0-24 h and AUC 24-48 h at 505.7 and 667.1 μg•h/mL, respectively. A strong correlation between nephrotoxicity and C trough was observed when the cutoff value was 18.9 μg/mL. AUC/MIC during the first 48 h was a determinant of vancomycin efficacy in Enterococcus infections but not for CoNS. C trough was not correlated with clinical outcome. Nephrotoxicity could be predicted using C trough and AUC for infections with both pathogens., (© 2024, The American College of Clinical Pharmacology.)

Low-density lipoprotein apheresis (LDL-A) is a blood purification therapy used to treat refractory ulcers in patients with arteriosclerosis obliterans. We describe a case of vancomycin treatment in a patient undergoing maintenance hemodialysis and LDL-A therapy and assess its impact on serum vancomycin concentration. The patient underwent LDL-A twice a week (Mondays and Fridays) and maintenance dialysis three times a week (Tuesdays, Thursdays, and Saturdays) for diabetic nephropathy associated with type 1 diabetes mellitus. Following the wound culture results, vancomycin was initiated with a 1.75 g administration post-dialysis. Serum vancomycin levels before and after LDL-A, measured on the subsequent day, exhibited only slight fluctuations within the intermeasurement variability range. Despite continuing vancomycin administration at the standard dose in patients undergoing hemodialysis, the serum concentration remained consistent, suggesting a minimal impact of LDL-A on vancomycin pharmacokinetics., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Vancomycin and tobramycin have traditionally been used in antibiotic spacers. In 2020, our institution replaced tobramycin with ceftazidime. We hypothesized that the use of ceftazidime/vancomycin (CV) in antibiotic spacers would not lead to an increase in treatment failure compared to tobramycin/vancomycin (TV)., Methods: From 2014 to 2022, we identified 243 patients who underwent a stage I revision for periprosthetic joint infection. The primary outcome was a recurrent infection requiring antibiotic spacer exchange. We were adequately powered to detect a 10% difference in recurrent infection. Patients who had a prior failed stage I or two-stage revision for infection, acute kidney injury prior to surgery, or end-stage renal disease were excluded. Given no other changes to our spacer constructs, we estimated cost differences attributable to the antibiotic change. Chi-square and t-tests were used to compare the two groups. Multivariable logistic regressions were utilized for the outcomes., Results: The combination of TV was used in 127 patients; CV was used in 116 patients. Within one year of stage I, 9.8% of the TV group had a recurrence of infection versus 7.8% of the CV group (P = .60). By final follow-up, results were similar (12.6 versus 8.6%, respectively, P = .32). Adjusting for potential risk factors did not alter the results. Cost savings for ceftazidime versus tobramycin are estimated to be $68,550 per one hundred patients treated., Conclusions: Replacing tobramycin with ceftazidime in antibiotic spacers yielded similar periprosthetic joint infection eradication success at a lower cost. While larger studies are warranted to confirm these efficacy and cost-saving results, our data justifies the continued investigation and use of ceftazidime as an alternative to tobramycin in antibiotic spacers., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Lactobacillus acidophilus is usually considered nonpathogenic and widely distributed in the human gastrointestinal and vaginal tract. In rare cases, lactobacilli may cause eye infections., Case Presentation: We report a 71-year-old man who experienced unexpected ocular pain and decreased visual acuity for one day after cataract surgery. He presented with obvious conjunctival and circumciliary congestion, corneal haze, anterior chamber cells, anterior chamber empyema, posterior corneal deposits, and pupil light reflection disappearance. This patient underwent the standard three-port 23-gauge pars plana vitrectomy and received the intravitreal perfusion of vancomycin at 1 mg/0.1 mL. The culture of the vitreous fluid produced Lactobacillus acidophilus., Conclusion: Acute Lactobacillus acidophilus endophthalmitis can occur after cataract surgery, which should be taken into consideration.

Competing Interests: Declaration of Competing Interest None of the authors declare a competing interest.

Background: Therapeutic drug monitoring (TDM) is an effective method for individualising antimicrobial therapy in critically ill patients. The 2021 ADMIN-intensive care unit survey studied a wide range of intensive care unit clinicians worldwide to gain their perspectives on antimicrobial TDM. This article reports the responses from this survey relating to TDM access, utilisation, and barriers., Methods: An online survey consisted of multiple-choice questions and 5-point Likert scales. The survey examined respondent's access to minimum inhibitory concentration (MIC) results, drug assays, and dosing software, as well as barriers to TDM., Results: The survey included 538 clinicians from 409 hospitals in 45 countries, with 71% physicians and 29% pharmacists. Despite most respondents having access to assays, 21% and 26% of respondents lacked access to vancomycin and aminoglycosides, respectively. In lower-income countries, almost 40% reported no access. Delayed drug assay turnaround time was the most significant barrier to TDM, particularly in lower-income countries. Routine access to MIC results was unavailable for 41% of respondents, with 25% of lower-income country respondents having no access to MIC or susceptibility reports., Conclusions: This global survey indicated that consistent TDM usage is hindered by assay access in some sites and the timeliness of assay results in others. Addressing barriers to TDM, particularly in low-income countries, should be a priority to ensure equitable access to affordable TDM., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Epidemiologic studies have shown decreasing vancomycin susceptibility among clinical Clostridioides difficile isolates, but the impact on patient outcomes is unknown. We hypothesized that reduced vancomycin susceptibility would be associated with decreased rates of sustained clinical response (SCR)., Methods: This multicenter cohort study included adults with C. difficile infection (CDI) treated with oral vancomycin between 2016 and 2021. Clostridioides difficile isolates underwent agar dilution vancomycin susceptibility testing, ribotyping, and Sanger sequencing of the vancomycin resistance vanR gene. Reduced susceptibility was defined as vancomycin minimum inhibitory concentration (MIC) >2 μg/mL. The primary outcome was 30-day SCR; secondary outcomes were 14-day initial cure, 30-day recurrence, and 30-day mortality. Exploratory analysis assessed the association between the VanR Thr115Ala polymorphism, susceptibility, and outcomes., Results: A high proportion (34% [102/300]) of C. difficile isolates exhibited reduced vancomycin susceptibility (range, 0.5-16 μg/mL; MIC50/90 = 2/4 μg/mL). Ribotype 027 accounted for the highest proportion (77.4% [41/53]) of isolates with reduced vancomycin susceptibility. Overall, 83% (249) of patients achieved 30-day SCR. Reduced vancomycin susceptibility was associated with lower rates of 30-day SCR (76% [78/102]) than vancomycin-susceptible strains (86% [171/198]; P = .031). A significantly lower rate of 14-day initial cure was also observed among individuals infected with strains with reduced vancomycin susceptibility (89% vs 96%; P = .04). Reduced susceptibility remained an independent predictor of 30-day SCR in multivariable modeling (odds ratio, 0.52 [95% confidence interval, .28-.97]; P = .04)., Conclusions: Reduced vancomycin susceptibility in C. difficile was associated with decreased odds of 30-day SCR and lower 14-day initial cure rates in the studied patient cohort., Competing Interests: Potential conflicts of interest. K. W. G. and A. J. G.-L. have received research funding from Merck. K. W. G. has received additional research funding from Acurx 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) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Staphylococcus aureus is a pathogenic bacterium responsible for a broad spectrum of infections, including cutaneous, respiratory, osteoarticular, and systemic infections. It poses a significant clinical challenge due to its ability to develop antibiotic resistance. This resistance limits therapeutic options, increases the risk of severe complications, and underscores the urgent need for new strategies to address this threat, including the investigation of treatments complementary to antibiotics. The evaluation of novel antimicrobial agents often employs animal models, with the zebrafish embryo model being particularly interesting for studying host-pathogen interactions, establishing itself as a crucial tool in this field. For the first time, this study presents a zebrafish embryo model for the in vivo assessment of bacteriophage efficacy against S. aureus infection. A localized infection was induced by microinjecting either methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA). Subsequent treatments involved administering either bacteriophage, vancomycin (the reference antibiotic for MRSA), or a combination of both via the same route to explore potential synergistic effects. Our findings indicate that the bacteriophage was as effective as vancomycin in enhancing survival rates, whether used alone or in combination. Moreover, bacteriophage treatment appears to be even more effective in reducing the bacterial load in S. aureus -infected embryos post-treatment than the antibiotic. Our study validates the use of the zebrafish embryo model and highlights its potential as a valuable tool in assessing bacteriophage efficacy treatments in vivo ., Competing Interests: The authors declare no conflict of interest.

Clostridioides difficile infection is the most common healthcare-associated infection in the United States, with potential life-threatening complications and a significant impact on the costs of care. Antibiotic stewardship as well as discontinuation of chronic acid suppressive therapy are key for its prevention and treatment. Effective infection management requires appropriate interpretation of diagnostic tests, as well as the use of vancomycin and fidaxomicin as first-line treatment. Novel treatments such as Bezlotoxumab, fecal microbiota transplant, and live biotherapeutic products are proven effective in recurrent C. difficile infection and address dysbiosis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rhodococcus hoagii is a gram positive actinomycete found in horses and cattle. Humans can be infected by ingestion or inhalation through contaminated food or soil. The organism usually infects immunosuppressed hosts with pneumonia being the common presentation. We present a case of an 89 years old, apparently immunocompetent host presenting with fever, encephalopathy and arthritis who grew Rhodococcus hoagii in blood and synovial fluid, The patient responded well to a combination of vancomycin, azithromycin and imipenem-cilastatin. Our case demonstrates that extra-pulmonary manifestations such as septic arthritis and bacteremia can be seen in immune competent hosts., 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 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Background: We sought to evaluate postoperative antibiotic practices in a large population of patients with necrotizing enterocolitis (NEC) and determine whether any regimens were associated with better outcomes., Methods: The Pediatric Health Information Systems (PHIS) database was queried to identify patients who underwent an intestinal resection for acute NEC between July, 2016 and June, 2021. Data regarding post-resection antibiotic therapy, cutaneous or intraabdominal infection, and fungal or antibiotic-resistant infection were collected., Results: 130 infants at 38 children's hospitals met inclusion criteria. Postoperative antibiotics were administered for a median of 13 days. The most frequently used antibiotics were vancomycin and piperacillin/tazobactam. Antibiotic duration greater than five days was not associated with a lower incidence of infection. No antibiotic was associated with a lower incidence of any of the complications assessed, although ampicillin was associated with more infections, overall. The incidence of fungal infection and treatment with a parenteral anti-fungal medication was greater with vancomycin. No antibiotic combination was used enough to be assessed., Conclusions: Administration of antibiotics for more than five days after resection for NEC was not associated with better infectious outcomes and no single antibiotic demonstrated superior efficacy. Consistent with prior studies, fungal infections were more frequent with vancomycin., Type of Study: Retrospective database study, level 3B., Level of Evidence: II., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gut-microbiota modulation shows promise in improving immune-checkpoint blockade (ICB) response; however, precision biomarker-driven, placebo-controlled trials are lacking. We performed a multicenter, randomized placebo-controlled, biomarker-stratified phase I trial in patients with ICB-naïve metastatic melanoma using SER-401, an orally delivered Firmicutesenriched spore formulation. Fecal microbiota signatures were characterized at baseline; patients were stratified by high versus low Ruminococcaceae abundance prior to randomization to the SER-401 arm (oral vancomycin-preconditioning/SER-401 alone/nivolumab + SER-401), versus the placebo arm [placebo antibiotic/placebo microbiome modulation (PMM)/nivolumab + PMM (NCT03817125)]. Analysis of 14 accrued patients demonstrated that treatment with SER-401 + nivolumab was safe, with an overall response rate of 25% in the SER-401 arm and 67% in the placebo arm (though the study was underpowered related to poor accrual during the COVID-19 pandemic). Translational analyses demonstrated that vancomycin preconditioning was associated with the disruption of the gut microbiota and impaired immunity, with incomplete recovery at ICB administration (particularly in patients with high baseline Ruminococcaceae). These results have important implications for future microbiome modulation trials. Significance: This first-of-its-kind, placebo-controlled, randomized biomarker-driven microbiome modulation trial demonstrated that vancomycin + SER-401 and anti-PD-1 are safe in melanoma patients. Although limited by poor accrual during the pandemic, important insights were gained via translational analyses, suggesting that antibiotic preconditioning and interventional drug dosing regimens should be carefully considered when designing such trials., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Although vancomycin is typically employed against methicillin-resistant Staphylococcus aureus (MRSA) infections, the optimal ratio of 24-h area under the concentration-time curve to minimum inhibitory concentration (AUC 24 /MIC) for severe or complicated infections lacks clear guideline recommendations. This study aimed to determine the target AUC 24 /MIC ratio associated with treatment outcomes of infections treated with vancomycin., Methods: This retrospective multicenter cohort study included adult patients receiving ≥ 5 days of vancomycin for severe/complicated MRSA infections (e.g., osteoarticular, pulmonary, endocarditis, etc.) between January 2018 and December 2023. The primary outcome was 30-day mortality, with secondary outcomes including clinical success, microbiological eradication, and nephrotoxicity. Receiver operating characteristic (ROC) curve analysis was used to identify the AUC 24 /MIC cutoff for 30-day mortality. Multivariate regression analysis was used to determine association between AUC 24 /MIC and outcomes., Results: This study included 82 patients. ROC identified a target AUC 24 /MIC of ≥ 505 for 30-day mortality. The overall 30-day mortality rate (22.0%) was significantly higher for below average AUC 24 /MIC cutoff (34.1%) than for above AUC 24 /MIC cutoff group (9.8%). Multivariate analysis confirmed AUC 24 /MIC of < 505 as an independent predictor (adjusted odds ratio, 5.001; 95% confidence interval, 1.335-18.75). The clinical success rate differed significantly between below- and above-cutoff groups, whereas microbiological eradication tended to favor the above-cutoff group. The nephrotoxicity rates were comparable between groups., Conclusions: In treating severe/complicated MRSA infections, vancomycin AUC 24 /MIC ratio ≥ 505 was independently associated with favorable 30-day mortality. Given the retrospective nature of this study, further prospective studies are essential to confirm the reliability of the target AUC 24 /MIC ratios., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Coagulase-negative Staphylococcus (CoNS) is the most frequent pathogen causing late-onset sepsis (LOS) in neonatal intensive care units (NICUs). Technical difficulties hinder blood culture (BC) collection and obtaining only one culture before initiating antibiotic therapy is a common practice. We sought to assess specific clinical information and CoNS cultures for the diagnosis of true bacteremia in the NICU., Study Design: This historical cohort study was conducted in NICUs at the Hadassah-Hebrew University Medical Center of Jerusalem in Israel. Clinical and laboratory data in every CoNS bacteremia were collected and compared between bacteremia groups as follows: true positive, two positive BCs; contaminant, one positive BC out of two; undefined, one BC obtained and found positive., Results: For 3.5 years, CoNS was isolated in 139 episodes. True positive was identified in 44 of 139 (31.7%), contaminant in 42 of 139 (30.2%), and the event was undefined in 53 of 139 (38.1%). Vancomycin treatment was more frequent in the true positive and undefined groups than the contaminant group (100, 90.6, and 73.8% respectively, p  = 0.001); treatment was also prolonged in these two groups ( p  < 0.001). No clinical variables were associated with true bacteremia on multivariable analysis., Conclusion: Diagnosis should definitely be based on at least two positive BCs, despite objective difficulties in obtaining BCs in neonates., Key Points: · CoNS is a frequent pathogen causing LOS in neonates.. · Due to technical difficulties, often only one culture is collected prior to antibiotic therapy.. · No clinical/laboratory variables were associated with the diagnosis of true CoNS bacteremia.., Competing Interests: None declared., (Thieme. All rights reserved.)

A 65-year-old woman with a history of peritoneal dialysis undergoing hemodialysis at our hospital presented with a fever after experiencing gastroenteritis symptoms. She had an implanted peritoneal dialysis catheter for draining chylous ascites. After commencing empirical treatment with meropenem, peritoneal effluent samples revealed an increased white blood cell count, and peritonitis was diagnosed. Enterococcus gallinarum was detected in blood and effluent cultures. Meropenem was changed to vancomycin based on susceptibility testing but subsequently restarted and thereafter changed to ampicillin following exacerbation of peritonitis. Finally, catheter removal led to complete recovery. E. gallinarum is vancomycin-resistant and a rare cause of peritonitis.

Study Design: Retrospective Case-Control series., Objective: The objective of this study is to define the overall postoperative rate of surgical site infection (SSI) in patients undergoing spine surgery and examine the effects of intrawound Vancomycin on postoperative infection rates., Summary of Background Data: Surgical site infections (SSI) account for 22% of all health care-associated infections. The use of intrawound Vancomycin in an attempt to reduce the incidence of postoperative SSI has not been sufficiently evaluated in the existing literature., Methods: All spine surgeries (n=19,081) from our institution were reviewed from 2003 to 2013. All cases of verified SSI were identified from the database. Cases were then matched to controls in a 1:1 fashion based on age, gender, and date of surgery (+/-30 d). Patient demographics, comorbidities, estimated blood loss, duration of surgery, intrawound administration of Vancomycin, and smoking status were evaluated., Results: At total of 316 cases of SSI after spine surgery were identified, representing an infection rate of 1.7%. The mean follow-up for cases and controls was 31.5 and 41.6 months, respectively. OR for intrawound Vancomycin was 0.44 (95% CI 0.23-0.88, P =0.019). OR for BMI greater than 30 was 1.63 (95% CI 1.04-2.56, P =0.03)., Conclusions: In this large cohort of spine surgery patients, administration of intrawound Vancomycin was associated with a significant reduction in postoperative surgical site infections. Further studies are needed to determine appropriate dosing and application as well as long-term safety in spine surgery., Competing Interests: A.N.: American Orthopaedic Association: Board or committee member; AO Spine: Research support; Cervical Spine Research Society: Board or committee member; Lumbar spine research society: Board or committee member; Pfizer: Research support; Scoliosis Research Society: Board or committee member; Synthes: Research support; Techniques in Orthopedics: Editorial or governing board; Vikon Surgical: Unpaid consultant. B.F.: Medtronic: Other financial or material support. M.Y.: AAOS: Board or committee member; Journal of Biomedical Materials Research-J. Wiley, Inc.: Editorial or governing board; K2M, Inc.: Paid consultant; Medtronic: Paid consultant; Society of Military Orthopaedic Surgeons: Board or committee member; Techniques in Orthopedics: Editorial or governing board. P.H.: Minnesota Orthopedic Society: Board or committee. E.B.: Pfizer: Research support; UpToDate: Publishing royalties, financial or material support; PI Strive Study; Pfizer vaccine study trial patients undergoing multilevel spine fusion. B.C.: DePuy, A Johnson & Johnson Company: IP royalties; Lumbar Spine Research Society: Board or committee member; Spine Study Group: Board or committee member; SpinologyTenex: Stock or stock Options; Stryker: IP royalties; Wolters Kluwer Health-Lippincott Williams & Wilkins: Publishing royalties, financial or material support; Zimmer: IP royalties. The remaining authors (Z.P., R.L.H., and A.S.S.) declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Clostridioides difficile (formerly Clostridium difficile) has been regarded as an 'urgent threat' and a significant global health problem, as life-threatening diarrhoea and refractory recurrence are common in patients with C. difficile infection (CDI). Unfortunately, the available anti-CDI drugs are limited. Recent guidelines recommend fidaxomicin and vancomycin as first-line drugs to treat CDI, bezlotoxumab to prevent recurrence, and faecal microbiota transplantation for rescue treatment. Currently, researchers are investigating therapeutic antibacterial drugs (e.g. teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571), preventive medications against recurrence (e.g. Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2), primary prevention strategies (e.g. vaccine, ribaxamase, and DAV132) and other anti-CDI medications in the preclinical stage (e.g. Raja 42, Myxopyronin B, and bacteriophage). This narrative review summarises current medications, including newly marketed drugs and products in development against CDI, to help clinicians treat CDI appropriately and to call for more research on innovation., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)