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The current recommendation for therapeutic monitoring of vancomycin has recently suggested AUC-guided dosing in patients with serious methicillin-resistant Staphylococcus aureus infections. The study objective was to evaluate mathematical equations and trapezoidal methods for calculating the 24h area under the plasma vancomycin concentration-time curve (AUC24). The analysis of plasma vancomycin concentrations was performed in 20 adult patients treated with intravenous vancomycin. For each patient, AUC24 was estimated using two methods including, equation and trapezoidal calculation. The AUC24 from two methods was analyzed for correlation. The correlation between the equation and trapezoidal methods was strong. The coefficient of determination (R²) values was greater than .99. The two plasma vancomycin concentrations to achieve the highest correlation were concentration at 2.5 to 3 h after starting the infusion and concentration at 1 h before the next dose. Moreover, the AUC24 calculation from trapezoidal and equation methods showed that 19 out of 20 patients (95%) had AUC24 of more than 400mg-h/L, and more than 50% in this group had AUC24/MIC greater than 600. Of those patients with AUC-trapezoidal >600, 15.38% of patients had trough under 15mg/L, 15.38% of patients had trough in the range 15 to 20mg/L and 69.23% of patients had trough more than 20mg/L. The results of AUC-equation were similar to those of the AUC-trapezoidal method. Our study confirmed that the AUC monitoring is more appropriate than the trough vancomycin concentration. Given these considerations, the AUC-equation method is better and more practical to use in part of a point-of-care treatment, especially in the part of the Bayesian program is not available. The best sampling time point of the peak concentration was 0.5-1 h after 2-h infusion. [ABSTRACT FROM AUTHOR]

Universal area-under-the-curve (AUC) guided vancomycin therapeutic drug monitoring (TDM) is resource-intensive, cost-prohibitive, and presents a paradigm shift that leaves institutions with the quandary of defining the preferred and most practical method for TDM. We report a step-by-step quality improvement process using 4 plan-do-study-act (PDSA) cycles to provide a framework for development of a hybrid model of trough and AUC-based vancomycin monitoring. We found trough-based monitoring a pragmatic strategy as a first-tier approach when anticipated use is short-term. AUC-guided monitoring was most impactful and cost-effective when reserved for patients with high-risk for nephrotoxicity. We encourage others to consider quality improvement tools to locally adopt AUC-based monitoring. [ABSTRACT FROM AUTHOR]

The 24-hour vancomycin area under the serum concentration-time curve (AUC 24 ) divided by the minimum inhibitory concentration (MIC) (AUC 24 /MIC) is more closely related to patient outcomes than serum trough concentrations (C trough ). Two-point simplified equations for calculating AUC based on serum peak concentrations (C peak ) and C trough , named equation A (EqA) and equation B (EqB), have recently been adopted into clinical use for adult pediatric patients. We aimed to find the agreement between predicted AUC 24 using the reference method (ref) relative to EqA and EqB and the correlation between C trough and AUC 24 . From June to December 2018, 43 pediatric patients with normal renal function, receiving 15 mg/kg of vancomycin intravenously every 6 hours, were enrolled. The pediatric patients' median age was 2.2 years (range 0.1-15.3). At steady state, vancomycin C peak and C trough were measured at 2 hours after infusion completion and within 30 minutes before the next dosing, respectively. AUC 24 was estimated using ref, EqA, and EqB. From Bland-Altman analysis, the 2 AUC 24 s estimated by ref and EqA showed less bias than those estimated by ref and EqB (bias 1.3 and -72.1 mg⋅h/L, respectively). C trough and AUC 24 using either ref or EqA were correlated more closely (r 2 = 0.94) than with EqB (r 2 = 0.86). Assuming a vancomycin MIC of 1 mg/L, an AUC 24 ≥400 mg⋅h/L was targeted. Regardless of the method used, AUC 24 ≥400 mg⋅h/L was never seen with C trough <8 mg/L but was always seen with C trough >10 mg/L. In conclusion, EqA based on the 2 measured serum concentrations was sufficiently accurate for AUC 24 estimation. C trough >10 mg/L correlated highly to AUC 24 ≥400 mg⋅h/L., (© 2019, The American College of Clinical Pharmacology.)

Study Objective: The preferred antibiotic salvage regimen for persistent methicillin‐resistant Staphylococcus aureus bacteremia (MRSAB) is unclear. We sought to evaluate the effectiveness and safety of vancomycin plus ceftaroline for persistent MRSAB. The primary outcome was time to MRSAB clearance post‐ceftaroline initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90‐day readmission for MRSAB, 90‐day all‐cause mortality, MRSAB‐related mortality, and incidence of antibiotic‐associated adverse effects. Design: Single‐center, retrospective cohort study between January 1, 2016, and December 31, 2021. Setting: State University of New York Upstate University Hospital, a 748‐bed tertiary care, academic medical center in Syracuse, NY. Patients Adult patients were included if they had blood cultures positive for MRSA ≥72 h, received vancomycin monotherapy initially, and received vancomycin plus ceftaroline for ≥24 h. Patients were excluded if they received other anti‐MRSA antibiotics, were pregnant, or were incarcerated. Of the 178 patients identified, 30 unique patients were evaluated. Measurements and Main Results: Patients were medically complex with a median Pitt bacteremia score of 3, 63.3% (19/30) were admitted to the intensive care unit, and 66.7% (20/30) had infective endocarditis. Vancomycin‐associated acute kidney injury was observed in 10% (3/30) of patients, which resulted in dose adjustments. No patients experienced ceftaroline‐associated neutropenia or Clostridioides difficile infection, but 6.7% (2/30) developed a rash attributed to ceftaroline. Median time to MRSAB clearance post‐ceftaroline initiation was 2.6 days. Microbiologic cure occurred in nearly all patients 96.7% (29/30). Median hospital length of stay was 19.5 days, and 6.7% (2/30) of patients had 90‐day readmission for MRSAB. 90‐day all‐cause mortality and MRSAB‐related mortality occurred in 26.7% (8/30) and 13.3% (4/30) of patients, respectively. Conclusions: Vancomycin plus ceftaroline may represent an effective and well‐tolerated salvage regimen option for persistent MRSAB. [ABSTRACT FROM AUTHOR]

The most recent consensus guidelines for dosing and monitoring vancomycin recommended the use of area‐under‐the‐curve with Bayesian estimation for therapeutic monitoring. As this is a modern concept in the practice of clinical pharmacy, the main objective of this review is to introduce the fundamentals of Bayesian estimation and its mathematical application as it relates to vancomycin therapeutic drug monitoring. In addition, we aim to identify pharmacokinetic (PK) software programs that incorporate Bayesian estimation for vancomycin dosing and to describe the PK models utilized in those software programs for the adult population. Twelve software programs that utilize Bayesian estimation were identified, which included: Adult and Pediatric Kinetics, Best Dose, ClinCalc, DoseMeRx, ID‐ODS, InsightRx, MwPharm++, NextDose, PrecisePK, TDMx, Tucuxi, and VancoCalc. The software programs varied in the population PK models used as the Bayesian a priori. With the presence of various vancomycin Bayesian software programs, it is important to choose those that utilize PK models reflective of the specific patient population. [ABSTRACT FROM AUTHOR]

Background Bacterial infections such as osteomyelitis and endocarditis routinely require several weeks of treatment with intravenous (IV) antimicrobials. Outpatient parenteral antimicrobial therapy (OPAT) programs allow patients to receive IV antimicrobials in an outpatient clinic or at home. The outcomes and costs of such treatments remain uncertain. Methods We conducted a retrospective observational cohort study over a 5-year study interval (1 June 2012 to 31 March 2018) using population-based linked administrative data from British Columbia, Canada. Patients receiving OPAT following a hospitalization for bacterial infection were matched based on infection type and implied duration of IV antimicrobials to patients receiving inpatient parenteral antimicrobial therapy (IPAT). Cumulative adverse events and direct healthcare costs were estimated over a 90-day outcome interval. Results In a matched cohort of 1842 patients, adverse events occurred in 35.6% of OPAT patients and 39.0% of IPAT patients (adjusted odds ratio, 1.04 [95% confidence interval {CI},.83–1.30; P =.61). Relative to IPAT patients, OPAT patients were significantly more likely to experience hospital readmission (30.5% vs 23.0%) but significantly less likely to experience Clostridioides difficile diarrhea (1.2% vs 3.1%) or death (2.0% vs 8.8%). Estimated mean direct healthcare costs were $30 166 for OPAT patients and $50 038 for IPAT patients (cost ratio, 0.60; average cost savings with OPAT, $17 579 [95% CI, $14 131–$21 027]; P <.001). Conclusions Outpatient IV antimicrobial therapy is associated with a similar overall prevalence of adverse events and with substantial cost savings relative to patients remaining in hospital to complete IV antimicrobials. These findings should inform efforts to expand OPAT use. [ABSTRACT FROM AUTHOR]

Introduction: The latest vancomycin therapeutic drug monitoring guidelines for serious MRSA infections have made a pivotal change in dosing, switching from targeting trough levels to AUC dosing. Because of these new recommendations, antimicrobial stewardship programs across the country are tasked with implementing AUC based dosing. Objectives: To assess plans for institutional adoption of vancomycin AUC dosing programs and perceptions of currently used programs in hospitals across the US. Methods: An electronic survey was distributed to members of the American College of Clinical Pharmacy IDprn Listserv and American Society of Health-System Pharmacists between May and June 2020 to assess current institutional vancomycin dosing. Institutional program use and multiple software user parameters were analyzed using descriptive statistics. Results: Two hundred two pharmacists responded to the survey with the majority practicing in institutions with 251-500 beds. Most respondents have yet to implement AUC dosing (142/202, 70.3%) with many of them planning to do so in the next year (81/142, 57.0%). Of those that already implemented AUC dosing programs, purchased Bayesian software (23/60, 38.3%) and homemade software (21/60, 35.0%) were the 2 methods most frequently utilized. Purchased Bayesian software users were more likely to recommend their software to other institutions and ranked user friendliness higher compared to non-purchased software. Conclusion: Most respondents have not made the switch to vancomycin AUC dosing, but there is a growing interest with many institutions looking to adopt a program within the next year. [ABSTRACT FROM AUTHOR]

Objective: Pregnancy and postpartum infective endocarditis (PPIE), although uncommon, is a very serious condition. To describe cases of infectious endocarditis (IE) in in a cohort of adults with IE in a Brazilian center and to review data from the recent literature on the subject. Methods: Cases of definite IE by the modified Duke criteria in adults were retrieved in a contemporary cohort of adults with IE from January 2006 to December 2020. Literature review on the topic was carried out and case reports on PPIE from 2014 to 2020 were compiled. Results: Two cases of PPIE were found in 401 adult patients with IE, with a prevalence of 0.5% in the cohort, of 2/139 (1.4%) among women and 2/83 (2.4%) of women of reproductive age (18 -49 years) in this same cohort. The search for published case reports from 2014 to 2020 resulted in 61 episodes of PPIE; in these, 7 pregnant women (11.4%), 10 fetuses (16.4%) and 1 premature newborn (1.6%) died. There was a previous valve predisposition in 12 (19.7%) cases and intravenous drug use in 14(23%). Left-sided valves were the most frequently affected in 41 (67.2%) of the cases. The most common isolated infectious agent was methicillin sensitive Staphylococcus aureus in 18/61 (29.5%) patients, although as a group, oral viridans streptococci accounted for 16/61 (26.2%). Valve surgery was done for 70% of patients. Conclusions: Intravenous drug use remained to be the main risk factor for IE. Mortality remained high for mothers and their children, despite the fact surgery was done more frequently in the recent cases. In the case of fever without an obvious focus in pregnant or post-partum women, the diagnosis of IE must be readily considered, especially in those with prosthesis and/or intravenous drug use. [ABSTRACT FROM AUTHOR]

A patient with end-stage renal disease received 2 doses of dalbavancin for methicillin-resistant Staphylococcus aureus (MRSA) arteriovenous fistula infection and presented 5 weeks later with infective endocarditis secondary to vancomycin, daptomycin, and dalbavancin nonsusceptible MRSA. Resistance was associated with walK and scrA mutations, reduced long-chain lipid content, and reduced membrane fluidity. [ABSTRACT FROM AUTHOR]

Background: Outcomes following andexanet alfa reversal of factor Xa inhibitors in patients requiring urgent or emergent invasive procedures are lacking. This study aimed to describe efficacy and safety outcomes following andexanet alfa administration within 24 h of an invasive procedure. Methods: This single‐center, observational, retrospective study included patients who received andexanet alfa within 24 h of an invasive or surgical procedure. The primary outcome was hemostatic efficacy graded as excellent, good, or poor using similar definitions to the ANNEXA‐4 criteria. Secondary outcomes included hospital discharge disposition, intensive care unit (ICU) and hospital length of stay, 30‐day mortality, 30‐day thromboischemic event rates, and serum coagulation assay changes pre‐ and postreversal. Results: Forty‐four patients met inclusion criteria; of these, 27 (62.8%) received apixaban and 16 (37.2%) were treated with rivaroxaban prior to admission. The indications for reversal were categorized as intracranial (n = 20 [45.5%]) or extracranial (n = 24 [54.5%]) sites. Majority of patients required emergent operative procedures (18 [40.9%]), followed by invasive device placement (10 [22.7%]) or arterial embolization (9 [20.5%]). Thirty‐eight (86.4%) patients were able to be adequately graded for hemostatic efficacy. Overall, 30 (78.9%) patients achieved excellent or good hemostasis within 24 h after periprocedural administration of andexanet alfa (19 [82.6%] apixaban vs. 11 [78.6%] rivaroxaban; 12 [80.0%] intracranial events vs. 18 [78.3%] extracranial events). Discharge disposition was most often to a short‐ or long‐term care facilities (27 [61.4%]). Thirty‐day mortality and thromboischemic complications occurred in 15 (34.1%) and 12 (27.3%) patients, respectively. Prothrombin time and antifactor Xa assay results were significantly decreased after andexanet alfa administration (p < 0.05) while thromboelastogram assay values (reaction time, kinetic time, and activated clotting time) showed nonsignificant changes pre‐ versus postreversal. Conclusion: Andexanet alfa may be used for urgent or emergent reversal of apixaban and rivaroxaban peri‐procedurally with promising hemostatic outcomes. Further prospective, comparative clinical research is warranted. [ABSTRACT FROM AUTHOR]

Several guidelines advise to monitor therapeutic LMWH therapy with peak anti-Xa concentrations in renal insufficiency with subsequent dose adjustments. A better understanding of the clinical association between peak anti-Xa concentrations and clinical outcomes is mandatory, because misunderstanding this association could lead to erroneous, and potentially even harmful, LMWH dose adjustments We reviewed the evidence of the widely applied therapeutic window for anti-Xa peak concentrations and report on the evidence for pharmacokinetic dose reduction in renal insufficiency, limitations of peak and trough anti-Xa concentration monitoring. The added value of peak anti-Xa monitoring in patients with renal insufficiency, receiving a dose reduced for pharmacokinetic changes, is not supported by data. Enoxaparin and nadroparin should be adjusted to 50–65% and 75–85% of the original dose for patients with a creatinine clearance (CrCL) of <30 ml/min and 30–60 ml/min, respectively. Tinzaparin should be adjusted to around 50% of the original dose for patients with a CrCL of <30 ml/min. In case anti-Xa monitoring is applied, trough concentration anti-Xa monitoring is preferred over peak monitoring, aiming at a maximum concentration of 0.4 IU/mL for once-daily dosed tinzaparin and 0.5 IU/mL for twice-daily dosed enoxaparin and nadroparin. [ABSTRACT FROM AUTHOR]

Objective: The transition to area under the curve (AUC) vancomycin monitoring requires substantial updates in pharmacy policies and procedures. The study facility was tasked with transitioning from a consult-based collaborative agreement to an automatic pharmacist management policy on all intravenous (IV) vancomycin orders. The purpose of this quality assessment (QA) study was to evaluate the effectiveness of this transition. Methods: The primary outcome was the proportion of patients with pharmacist assessment of pharmacokinetics and dosing with documentation in IV vancomycin treated patients from January-June 2020. Secondary outcomes included the proportion of AUC24 levels within therapeutic range, the incidence of acute kidney injury (AKI) and treatment failures in patients treated ≥72 hours compared to a historical, trough-based cohort. Results: There were 88 patients in the QA analysis with 100% having a pharmacist assessment with documentation. There were 34 patients treated ≥72 hours in the AUC group, 36 in the trough-based group. AUC24 fell within desired range in 45% of monitored patients. Rates of AKI (9% vs 11%, p = 0.75) and treatment failures were similar (3% vs 0%, p = 0.3). Conclusion: The transition from consult-based to an automatic pharmacy management agreement was successful with similar safety and efficacy compared to a historical trough-based cohort. [ABSTRACT FROM AUTHOR]

Background: New guidance recommends area under the curve/minimum inhibitory concentration (AUC/MIC) instead of trough-based monitoring for vancomycin therapy. While this transition has demonstrated improved safety and efficacy in large, tertiary centers, this has not been assessed in the primary hospital setting. Objective: The primary objectives were to evaluate the efficacy and safety of AUC/MIC monitoring in inpatient veterans treated with intravenous vancomycin for ≥72 hours compared to a historical cohort of trough-based monitoring. Methods: This was a retrospective, quasi-experimental study over 2 five-month study periods. Efficacy was evaluated by comparing clinical failure rates as defined by a persistent fever, clinical deterioration, or escalation of gram-positive therapy. Safety was determined by the incidence of acute kidney injury (AKI) defined by an acute increase in serum creatinine ≥0.3 mg/dL over 48 hours. Results: 25 patients met the criteria in the before group and 19 in the after group. Efficacy was equivalent between groups; no patients exhibited clinical failure of vancomycin therapy. In the before group, 2 patients (8%) met defined criteria for AKI, while none in the after group experienced AKI (P = 0.21). Total vancomycin exposure was similar between groups (P = 0.56). Conclusion: AUC-based monitoring was equally efficacious as trough-based monitoring with similarly low rates of AKI. [ABSTRACT FROM AUTHOR]

Appropriate prescribing of anti-infectives is a public health challenge. In our hospital, clinical microbiologists (clinical microbiology mobile unit, UMMc) and clinical pharmacists (clinical pharmacy, PHAc) carry out interventions on anti-infective prescriptions to improve practices. Our main objective was to evaluate the acceptance of UMMc and PHAc interventions on anti-infective prescriptions by quantifying the rate of prescription change 24 h after intervention. The secondary objective was to characterize the type of intervention and associate the rate of change for each. All prescriptions are computerized, and interventions traced via DxCare® software, which feeds a local data warehouse (HEGP-CDW). This descriptive, retrospective, single-center, uncontrolled study was conducted from January 2015 to December 2018. The data were extracted over this period from the data warehouse and analyzed using R software. UMMc interventions were accepted 72.2% of the time and PHA interventions 87.3%. The types of interventions found were mostly dose adjustments (61.1% for the UMMc and 54.2% for the PHAc) and proposals to change or stop a drug. Interventions have an impact on anti-infective prescriptions and are generally followed by clinicians. For the category "discontinuation of a molecule", almost half of the advice from the UMMc was refused. The collaboration between the UMMc and PHAc should be reinforced to improve acceptance. [ABSTRACT FROM AUTHOR]

Background Limited data are available in the United States on the 12-month epidemiology, outpatient (OP) antibiotic treatment patterns, outcomes, and costs associated with complicated urinary tract infections (cUTIs) in adult patients. Methods A retrospective observational cohort study of adult patients with incident cUTIs in IBM MarketScan Databases between 2017 and 2019 was performed. Patients were categorized as OP or inpatient (IP) based on initial setting of care for index cUTI and were stratified by age (<65 years vs ≥65 years). OP antibiotic treatment patterns, outcomes, and costs associated with cUTIs among adult patients over a 12-month follow-up period were examined. Results During the study period, 95 322 patients met inclusion criteria. Most patients were OPs (84%) and age <65 years (87%). Treatment failure (receipt of new unique OP antibiotic or cUTI-related ED visit/IP admission) occurred in 23% and 34% of OPs aged <65 years and ≥65 years, respectively. Treatment failure was observed in >38% of IPs, irrespective of age. Across both cohorts and age strata, >78% received ≥2 unique OP antibiotics, >34% received ≥4 unique OP antibiotics, >16% received repeat OP antibiotics, and >33% received ≥1 intravenous (IV) OP antibiotics. The mean 12-month cUTI-related total health care costs were $4697 for OPs age <65 years, $8924 for OPs age >65 years, $15 401 for IPs age <65 years, and $17 431 for IPs age ≥65 years. Conclusions These findings highlight the substantial 12-month health care burden associated with cUTIs and underscore the need for new outpatient treatment approaches that reduce the persistent or recurrent nature of many cUTIs. [ABSTRACT FROM AUTHOR]

Background: A hospital pharmacy foundation residency training program has been introduced in Australia, modelled on residency programs established in other countries. The program aims to support the professional development of early-career hospital pharmacists, in both clinical and non-clinical roles. Pharmacy educators are usually tasked with the implementation and maintenance of this program. This qualitative, longitudinal study aimed to investigate hospital pharmacy educators' expectations, perceptions and experiences with implementing and developing their residency program. Methods: Qualitative data were collected at two timepoints, approximately 24 months apart, using either focus groups or interviews with pharmacy educators who were directly involved in the implementation of the residency program at their respective hospitals. During the early phases of implementation, and approximately 24 months later, participants were asked about their experiences and expectations of the residency program as well as any changes that had occurred within the residency program over time. Results: Four focus groups and three semi-structured interviews were held with pharmacy educators and senior pharmacists from different hospital settings. These were audio recorded and transcribed verbatim. Transcripts were inductively analysed via thematic analysis. Fifteen hospital pharmacy educators and senior hospital pharmacists participated in the initial focus groups and interviews, and seven educators were retained for follow-up. Four main themes were established from the discussions: participants had great expectations of a positive impact of the residency on their workplace and residents' professional development; substantial effort, support and resources were needed to implement and maintain a residency program; self-motivation and engagement is needed by residents to succeed and experience timely completion and career acceleration; and lastly a balance between standardisation, consistency and flexibility in delivering the residency needs to be found. The role of educators changed with the implementation of a residency, with the addition of more managerial and supervisory aspects. Conclusion: The Australian hospital pharmacy foundation residency program is a complex workplace training program with multiple factors and prerequisites influencing its implementation, development and outcomes. Pharmacy educators are central to the successful implementation and ongoing sustainability of a residency program. They may benefit from formal training and qualifications to support their role. [ABSTRACT FROM AUTHOR]

Several natural antimicrobial peptides (AMPs), including the novel semisynthetic lipoglycopeptide antibiotics telavancin, dalbavancin, and oritavancin, have been approved for clinical use to address the growing problem of multiple antibiotic‐resistant Gram‐positive bacterial infections. Nevertheless, the efficacy of these antibiotics has already been compromised. The SARS‐CoV‐2 pandemic led to the increased clinical use of all antibiotics, further promoting the development of bacterial resistance. Therefore, it is critical to gain a deeper understanding of the role of resistance mechanisms to minimize the consequential risks of long‐term antibiotic use and misuse. Here, we summarize for the first time the current knowledge of resistance mechanisms that have been shown to cause resistance to clinically used AMPs, with particular focus on membrane proteins that have been reported to interfere with the activity of AMPs by affecting the binding of AMPs to bacteria. [ABSTRACT FROM AUTHOR]

Vancomycin was introduced nearly 65 years ago and remains the standard antibiotic for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Staphylococcus aureus remains highly susceptibility to vancomycin (>97%). Despite this, MRSA treatment failure with vancomycin is high in complicated bacteremia. Additionally, vancomycin can cause nephrotoxicity, leading to new therapeutic drug monitoring guidance. This demonstrates how difficult it is to dose vancomycin in a way that is both efficacious and safe, especially during long courses of therapy. Often underappreciated are the cost, resources, and complexity of vancomycin care at a time when alternative antibiotics are becoming cost comparable. This perspective highlights a bigger picture of how the treatment repertoires of many other diseases have changed and advanced since vancomycin's introduction in the 1950s, yet the vancomycin MRSA treatment standard remains. While vancomycin can still have a role, 65 years may be a practical retirement age for vancomycin in highly complex endovascular infections. [ABSTRACT FROM AUTHOR]

Background In the Netherlands, home treatment with intravenous antimicrobial therapy is a relatively new concept. Although several studies have shown that outpatient parenteral antimicrobial therapy (OPAT) can be administered safely, people receiving antimicrobials at home remain at risk for adverse events, including readmission. Aim The aim of our retrospective study was to identify risk factors for readmission in patients discharged with OPAT. Method Patients who were at least 18 years or older, discharged with OPAT between January 2016–December 2018 were included. Variables that were collected consisted of baseline demographics, complications, readmission within 30 days and treatment failure. Multivariate logistic regression analysis was performed to identify risk factors for readmission. Results A total of 247 patients were included; the most common reason for OPAT was bone and joint infections (17%). Penicillin (37%), cephalosporin (26%) and vancomycin/aminoglycoside (15%) were the most commonly prescribed antimicrobials. Among patients receiving medication subject to therapeutic drug monitoring (i.e. aminoglycosides or vancomycin), 51% (19/37) received weekly therapeutic drug monitoring. Receiving aminoglycosides or vancomycin (adjusted OR 2.05; 95% CI 1.30–3.25, p < 0.05) and infection of prosthetic material (adjusted OR 2.92, 95% CI 1.11–7.65, p < 0.05) were independent risk factors associated with readmission. Conclusion Although patients receiving medication subject to therapeutic drug monitoring are at higher risk of readmission, only half of the patients discharged with aminoglycosides or vancomycin were monitored according to IDSA guidelines. A specialized team in charge of monitoring patients with OPAT is more likely to increase the rate of monitoring to prevent readmissions and complications. [ABSTRACT FROM AUTHOR]

The recently released revised vancomycin consensus guideline endorsed area under the concentration‐time curve (AUC) guided monitoring. Means to AUC‐guided monitoring include pharmacokinetic (PK) equations and Bayesian software programs, with the latter approach being preferable. We aimed to evaluate the predictive performance of these two methods when monitoring using troughs or peaks and troughs at varying single or mixed dosing intervals (DIs), and evaluate the significance of satisfying underlying assumptions of steady‐state and model transferability. Methods included developing a vancomycin population PK model and conducting model‐informed precision dosing clinical trial simulations. A one‐compartment PK model with linear elimination, exponential between‐subject variability, and mixed (additive and proportional) residual error model resulted in the best model fit. Conducted simulations demonstrated that Bayesian‐guided AUC can, potentially, outperform that of equation‐based AUC predictions depending on the quality of model diagnostics and met assumptions. Ideally, Bayesian‐guided AUC predictive performance using a trough from the first DI was equivalent to that of PK equations using two measurements (peak and trough) from the fifth DI. Model transferability diagnostics can guide the selection of Bayesian priors but are not strong indicators of predictive performance. Mixed versus single fourth and/or fifth DI sampling seems indifferent. This study illustrated cases associated with the most reliable AUC predictions and showed that only proper Bayesian‐guided monitoring is always faster and more reliable than equations‐guided monitoring in pre‐steady‐state DIs in the absence of a loading dose. This supports rapid Bayesian monitoring using data as sparse and early as a trough at the first DI. [ABSTRACT FROM AUTHOR]

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The updated vancomycin guideline and recent studies suggested that trough concentrations may result in underestimation of the actual area under the curve (AUC), leading to excessive dosing and nephrotoxicity. With limited data available on critically ill cancer patients, this study aimed to compare the two methods in this patient population. This was a 5‐year retrospective study on patients treated with vancomycin in the intensive care unit (ICU) of a comprehensive cancer center. The measured trough concentration was compared to Bayesian‐derived AUC/minimum‐inhibitory‐concentration (MIC), considering MIC as 1. Trough concentrations of 15–20 mg/L and AUC of 400–600 mg h/L were considered the targeted goal. Multivariate analysis was performed to identify factors associated with an AUC below the targeted goal. During the study period, 316 patients were included. The mean age was 54 years ±16 (SD); most patients had solid tumors (75%), and 11% had neutropenia. A targeted goal AUC and trough were recorded in 128 (41%) patients and in 64 (20%) patients, respectively. Of the 128 patients with targeted goal AUC, 31 (24%) had targeted goal trough concentrations and 91 (71%) had trough concentrations below 15 mg/L. Furthermore, among the patients with targeted goal trough concentration (n = 64), 33 (52%) had higher than targeted goal AUC. Augmented renal clearance (ARC), defined as a calculated creatinine‐clearance ≥130 ml/min, was associated with an AUC below the targeted goal. In a cohort of critically ill patients with cancer, over two‐thirds of the patients with a targeted goal Bayesian AUC/MIC had trough concentrations below the targeted goal. ARC was associated with AUC below the targeted goal. [ABSTRACT FROM AUTHOR]

Limited data exists regarding the clinical outcomes of andexanet alfa and four factor prothrombin complex concentrate (4F-PCC) for reversal of apixaban or rivaroxaban in the setting of intracranial hemorrhage (ICH). The objective of this study was to evaluate clinical outcomes of 4F-PCC and andexanet alfa for reversal of ICH associated with oral factor Xa inhibitors. This was a retrospective, single-center, case series evaluating hemostatic efficacy of patients receiving andexanet alfa) or 4F-PCC for reversal of apixaban or rivaroxaban after ICH. Secondary endpoints included in-hospital mortality, thrombotic complications, timing of reversal agents, intensive care unit and hospital length of stay, patient disposition, and 30-day readmission rate. During the study period, 21 patients received andexanet alfa and 35 received 4F-PCC. Hemostatic efficacy occurred in 64.7% of patients receiving andexanet alfa and 54.8% of receiving 4F-PCC. Thirty-day all-cause mortality was 45.2% for 4F-PCC and 30% for andexanet alfa. Thrombotic events were higher with 4F-PCC (31.4%) compared to andexanet alfa (14.3%). Median time from presentation to administration of reversal agent was 2.67 [1.75–4.13] hours with andexanet alfa and 1.73 [1.21–3.55] hours with 4F-PCC. Discharge to skilled nursing facilities and 30-day readmission were similar between groups. In this cohort, reversal with andexanet alfa and 4F-PCC differed in terms ofhemostatic efficacy and thrombotic events after ICH in patients anticoagulated with apixaban or rivaroxaban. [ABSTRACT FROM AUTHOR]

Background: Metformin has been used for the treatment of type 2 diabetes for over 60 years; however, its mechanism of pharmacological action is not fully clear. Different hypotheses exist regarding metformin distribution and redistribution mechanisms between plasma and erythrocytes/red blood cells (RBCs). Objective: We aimed to test the hypothesis that the metformin distribution between plasma and RBC occurs via concentration difference-driven passive transport and estimated transport rate coefficient values based on metformin concentration time series in plasma and RBCs from in vivo studies. Methods: An ordinary differential equation (ODE) system with two compartments was used to describe diffusion-based passive transport between plasma and RBCs. Metformin concentration time series in plasma and RBCs of 35 individuals were used for metformin transport parametrization. Plasma concentration has been approximated by biexponential decline. Results: A single passive transport coefficient, k = 0.044 ± 0.014 (h–1), can be applied, describing the uptake and release transport rate versus the linear equation v = k × (Mpl − MRBC), where Mpl is the metformin concentration in plasma and MRBC is the metformin concentration in RBCs. Conclusions: Our research suggests that passive transport can explain metformin distribution dynamics between plasma and RBCs because transport speed is proportional to the metformin concentration difference and independent of the transport direction. Concentration difference-driven passive transport can explain the mechanism of faster metformin distribution to RBCs the first few hours after administration, and faster release and domination of the redistribution transport rate after metformin concentration in plasma becomes smaller than in RBCs. [ABSTRACT FROM AUTHOR]

Purpose of Review: Antimicrobial stewardship within acute care is common and has been expanding to outpatient areas. Some inpatient antimicrobial stewardship tactics apply to outpatient parenteral antimicrobial therapy (OPAT) and complex outpatient antimicrobial therapy (COpAT) management, but differences do exist. Recent Findings: OPAT/COpAT is a growing area of practice and research with its own unique considerations for antimicrobial stewardship. Potential ideas for antimicrobial stewardship in the OPAT/COpAT setting include redesigning the regimen to COpAT instead of OPAT, ensuring the use of the shortest effective duration of antimicrobial therapy; using antimicrobials dosed less frequently, such as long-acting glycopeptides; optimizing antimicrobial susceptibility testing reporting for common OPAT/COpAT drugs; and establishing routine laboratory and safety monitoring. Future consensus is needed to determine validated OPAT program metrics and outcomes. Summary: As more focus is placed on outpatient antimicrobial stewardship, clinicians practicing in OPAT should publish more data regarding OPAT program methods and outcomes as they relate to antimicrobial stewardship. These can involve patient clinical outcomes, OPAT readmission rates, OPAT therapy completion, and central line-related complications. [ABSTRACT FROM AUTHOR]

Objective: To compare between current evidence of novel glycopeptides against vancomycin for the treatment of gram-positive bacterial infections. Methodology: A systematic review and meta-analysis was done. Major databases were searched for eligible randomized control trials that assessed clinical success, microbiological success and safety profile of novel glycopeptides versus vancomycin for infections caused by gram-positive bacteria. Results: This meta-analysis included eleven trials (7289 participants) comparing telavancin, dalbavancin and oritavancin with vancomycin. No differences were detected between novel glycopeptides and vancomycin for the treatment of skin and soft tissue infections (SSTIs) among modified intent-to-treat patients (OR: 1.04, CI: 0.92–1.17) as well as within the clinically evaluable patients (OR: 1.09, CI: 0.91–1.30). Data analysed from SSTIs, HAP and bacteremia studies on telavancin showed insignificant high clinical response in microbiologically evaluable patients infected with methicillin resistant Staphylococcus aureus (MRSA) (OR: 1.57, CI: 0.94–2.62, p: 0.08) and in the eradication of MRSA (OR: 1.39, CI: 0.99–1.96, P:0.06). Dalbavancin was non-inferior to vancomycin for the treatment of osteomyelitis in a phase II trial, while it was superior to vancomycin for the treatment of bacteremia in a phase II trial. Data analysed from all trials showed similar rates of all-cause mortality between compared antibiotics groups (OR: 0.67, CI: 0.11–4.03). Telavancin was significantly related with higher adverse events (OR: 1.24, CI: 1.07–1.44, P: <0.01) while dalbavancin and oritavancin were associated with significant fewer adverse events (OR: 0.73, CI: 0.57–0.94, p: 0.01; OR: 0.72, CI: 0.59–0.89, p: <0.01 respectively). Conclusion: Efficacy and safety profiles of both dalbavancin and oritavancin were the same as vancomycin in the treatment of gram-positive bacterial infections in different clinical settings, while telavancin might be an effective alternative to vancomycin in MRSA infections, but caution is required during its clinical use due to the high risk of adverse events, especially nephrotoxicity. [ABSTRACT FROM AUTHOR]

Background: Pharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia.Methods: A retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality.Results: A total of 37 patients were enrolled-26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia.Conclusions: In this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia. [ABSTRACT FROM AUTHOR]

Background Correct dosing and therapeutic drug monitoring (TDM) practices are essential when aiming for optimal vancomycin treatment. Objective To assess target attainment after initial dosing and dose adjustments, and to determine compliance to dosing and TDM guidelines. Setting Tertiary care university hospital in Belgium. Method A chart review was performed in 150 patients, ranging from preterm infants to adults, treated intravenously with vancomycin. Patient characteristics, dosing and TDM data were compared to evidence-based hospital guidelines. Main outcome measures Target attainment of vancomycin after initial dosing and dose adjustments. Results Subtherapeutic concentrations were measured in 68% of adults, in 76% of children and in 52% of neonates after treatment initiation. Multiple dose adaptations (median 2, Q1 1–Q3 2) were required for target attainment, whilst more than 20% of children and neonates never reached targeted concentrations. Regarding compliance to the hospital guideline, some points of improvement were identified: omitted dose adjustment in adults with decreased renal function (53%), delayed sampling (16% in adults, 31% in children) and redundant sampling (34% of all samples in adults, 12% in children, 13% in neonates). Conclusion Target attainment for vancomycin with current dosing regimens and TDM is poor in all age groups. Besides, human factors should not be ignored when aiming for optimal treatment. This study reflects an ongoing challenge in clinical practice and highlights the need for optimization of vancomycin dosing strategies and improvement of awareness of all health care professionals involved. [ABSTRACT FROM AUTHOR]

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The revised vancomycin guidelines recommend implementing AUC24-based therapeutic drug monitoring (TDM) using Bayesian methods in both adults and paediatrics. The motivation for this change was accumulating evidence showing aggressive dosing to achieve high troughs, as recommended in the first guidelines for adults and extrapolated to paediatrics, is associated with increased nephrotoxicity without improving clinical outcomes. AUC24-based TDM requires substantial resources that may need to be diverted from other valuable interventions. It can therefore be justified only after certain assumptions are shown to be true: (i) there is a clear relationship between vancomycin efficacy and/or toxicity and the proposed therapeutic range; and (ii) maintaining exposure within the target range with AUC24-based TDM improves clinical outcomes and/or decreases toxicity. In this review, we critically appraise the scientific basis for these assumptions. We find studies evaluating the relationship between vancomycin AUC24/MIC and efficacy in adults and children do not offer strong support for the recommended lower limit of the proposed therapeutic range (i.e. AUC24/MIC ≥400). Nephrotoxicity in children increases in a stepwise manner along the vancomycin exposure continuum but it is unclear if one parameter (AUC24 versus trough) is a superior predictor. Overall, evidence in children suggests good-to-excellent correlation between AUC24 and trough. Most importantly, there is no convincing evidence that the method of vancomycin TDM has a causal role in improving efficacy or reducing toxicity. These findings question the need to transition to resource-intensive AUC24-based TDM over retaining trough-based TDM with lower targets to minimize nephrotoxicity in paediatrics. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the acceptance rate of pharmacist recommendations in an interdisciplinary team for patients interviewed by the pharmacist versus those assessed by chart review. DESIGN: Retrospective chart review. SETTING: Interdisciplinary consultative team in an outpatient setting as part of a large academic health system provided care for "high utilizer" patients. PARTICIPANTS: Sixty-five patients at moderate to high risk of hospitalization who completed their first appointment with the team between March 1, 2019, and December 30, 2019. Most patients were 65 years of age or older and all had Medicare insurance. INTERVENTIONS: A pharmacist completed a chart review for all patients. A cohort of patients were also interviewed. Recommendations were recorded in the electronic medical record, discussed with the team, and forwarded to the patient's primary care provider. RESULTS: A total of 253 recommendations were made by pharmacists, with a significantly higher acceptance rate for patients who completed an interview with the pharmacist (40.7% vs. 28.4%; P = 0.046). Patientspecific factors resulting in higher acceptance rates in the interview group included age younger than 65 years (P = 0.013), 10 to 19 medications (P = 0.004), and mental health diagnosis (P = 0.02). CONCLUSION: The addition of an interview to chart review allowed pharmacists to make recommendations that were more likely to be accepted and therefore more clinically impactful. [ABSTRACT FROM AUTHOR]

Purpose: Levetiracetam is an antiepileptic medication commonly used in critical care areas for seizure treatment or prophylaxis. Compatibility data of levetiracetam with other critical care medications are limited, which can make administration challenging. This study aims to assess the physical Y-site compatibility of intravenous levetiracetam with some other commonly used critical care medications. Methods: Y-site administration was simulated by independently mixing levetiracetam with each of 11 selected medications in a 4-dram, colorless, screw-cap, glass vial, at a 1:1 ratio. Clinically used concentrations of each medication were compounded in 0.9% sodium chloride following United States Pharmacopeia chapter 797 standards. Physical compatibility was observed and assessed at 0, 15, and 30 minutes after mixing. Medication mixtures were considered physically incompatible if there was visual evidence of color change, gas evolution, haze, or particulate formation, pH change > 10%, or if they had an absorbance value > 0.010 A. Results: No evidence of physical incompatibility was observed during simulated Y-site testing with cisatracurium 1 mg/mL, dexmedetomidine 4 µg/mL, fosphenytoin 15 mg PE/mL, norepinephrine 16 mg/mL, norepinephrine 32 mg/mL, norepinephrine 64 mg/mL, piperacillin-tazobactam 33.75 mg/mL, propofol 10 mg/mL, vancomycin 5 mg/mL, or vasopressin 1 unit/mL when tested in 0.9% sodium chloride. Levetiracetam was incompatible with piperacillin-tazobactam 45 mg/mL. Conclusion: Levetiracetam 5 mg/mL in 0.9% sodium chloride was found to be physically compatible for 30 minutes with 10 of the 11 medications tested during simulated Y-site administration. [ABSTRACT FROM AUTHOR]

Vancomycin is commonly prescribed to hospitalized patients. Decades of pharmacokinetic/pharmacodynamic research culminated in recommendations to monitor the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration in order to optimize vancomycin exposure and minimize toxicity in the revised 2020 guidelines. These guideline recommendations are based on limited data without high-quality evidence and limitations in strength. Despite considerable effort placed on vancomycin therapeutic drug monitoring (TDM), clinicians should recognize that the majority of vancomycin use is empiric. Most patients prescribed empiric vancomycin do not require it beyond a few days. For these patients, AUC determinations during the initial days of vancomycin exposure are futile. This added workload may detract from high-level patient care activities. Loading doses likely achieve AUC targets, so AUC monitoring after a loading dose is largely unnecessary for broad application. The excessive vancomycin TDM for decades has been propagated with limitations in evidence, and it should raise caution on contemporary vancomycin TDM recommendations. [ABSTRACT FROM AUTHOR]

Background It is unclear which vancomycin area under the curve (AUC) values are most associated with risk for acute kidney injury (AKI). Methods This retrospective cohort study was undertaken to determine if vancomycin AUC >550 is associated with a higher rate of AKI than an AUC <550. Patients treated with vancomycin for at least 4 days at the VA St. Louis Health Care System from 1/1/2016 to 9/31/2018 were included. The primary outcome was AKI (defined as an increase in serum creatinine by 0.3 mg/dL or 50% from baseline). Secondary outcomes included length of stay, readmission in 30 days, and mortality in 30 days. A bivariate analysis was used to determine other potential factors affecting AKI rate, with significant variables (P  < .2) to be included in the multivariate logistic regression analysis to determine independent risk for AKI. Results Two hundred patients were included in the analysis; 100 patients with an AUC ≥550 and 100 with an AUC <550. Only mean vancomycin dose (1722.50 mg vs 2361.25 mg; P  < .05), mean AUC (465.88 vs 696.45; P  < .05), and peak SCr (1.22 mg/dL vs 1.48 mg/dL; P  = .015) were significantly different between groups (AUC <550 vs AUC ≥550, respectively). AKI occurred in 42% (42/100) of patients with AUC ≥550 compared with 2% (2/100) of patients with AUC <550 (P  < .05). Secondary outcomes were not different between the groups. In the bivariate analysis, age ≥70, CrCl <50 mL/min, and AUC ≥550 (odds ratio, 49.5; 95% CI, 10.1–242.3; P  < .05) were found to be independently associated with risk for developing AKI. Conclusions Patients with a vancomycin AUC ≥550 were found to have a significantly higher rate of AKI compared with those with an AUC <550. [ABSTRACT FROM AUTHOR]

OBJECTIVES A venous thromboembolism (VTE) is a blood clot that occurs secondary to vessel wall injury often from a central line insertion. Enoxaparin is often considered a first-line treatment in pediatrics for VTE due to its favorable kinetic profile. Enoxaparin monitoring for pediatric patients is accomplished through anti-Xa monitoring in which monitoring practices may vary between institutions. The objective of this study is to evaluate covariates in pediatric patients to determine which variables are most likely to be associated with enoxaparin dose changes as a result of anti-Xa monitoring. METHODS A single center, retrospective chart review was conducted in pediatric patients treated with enoxaparin for VTE over a 10-year period and who were assessed to determine covariates that lead to dose changes based on anti-Xa levels. Secondary outcomes described monitoring patterns at the University of New Mexico Children's Hospital. RESULTS Sixty-eight patients met inclusion criteria in which results showed that patients aged 2 to 5.9 months (p = 0.026), who had critical care status (p = 0.009), and who were of Native American ethnicity (p = 0.016) were likely to have an enoxaparin dose change at least once during their treatment regimen. The mean number of levels drawn were 7.5 per patient over a 6- to 12-week period, and doses were not frequently changed based on a confirmatory lab draw. However, many doses were adjusted based on the week 1 post-therapeutic level. CONCLUSIONS Patients of Native American ethnicity, younger than 6 months, and those admitted to the PICU were likely to have dose changes based on anti-Xa levels. [ABSTRACT FROM AUTHOR]

Purpose: Therapeutic drug monitoring guided by the area under the concentration-time curve (AUC-guided TDM) is recommended for vancomycin. However, validated efficient software remains elusive to popularize AUC-guided TDM in Japan. The aim of this study was to validate a newly developed web application, PAT, for AUC estimation. Methods: PAT was developed on the R ver. 3.6.2 platform for use with mobile phones and personal computers. AUC estimated by PAT (AUCPAT) was evaluated against the reference AUC (AUCREF) calculated with the log-linear trapezoidal rule using eight measured concentrations, or against AUC (AUCBM-P) calculated using an evaluated available software with clinical data. Results: Investigating the best sampling points with limited sampling, PAT produced the least bias using two concentrations at 1 h and 11 h after the end of infusion (slope 1.18, intercept −15.57, median AUCPAT/AUCREF 0.93 [range 0.81–1.24]), where only one estimation (6%) was out of the predetermined acceptable range of 0.8–1.2. Employment of only a trough concentration was more biased (AUCPAT/AUCREF range 0.73–1.30 for 11 h, AUCPAT/AUCREF range 0.62–1.40 for 23 h). In comparison with the evaluated software, AUCPAT was not biased against the AUCBM-P (slope 1.04, intercept −15.80, median AUCPAT/AUCBM-P 1.00 [range 0.86–1.10]). Conclusions: The new application using two concentrations was appropriately validated and might be efficient in popularizing the AUC-guided TDM of vancomycin. [ABSTRACT FROM AUTHOR]

Optimal vancomycin exposure is important to minimize treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We aimed to analyze the impact of initial vancomycin pharmacokinetic/pharmacodynamic (PK/PD) parameters, including the initial vancomycin C trough and the area under the curve (AUC)/minimal inhibitory concentration (MIC) on the outcomes of pediatric MRSA bacteremia. The study population consisted of hospitalized children aged between 2 months and 18 years with MRSA bacteremia, in whom C trough was measured at least one time within the time period of January 2010 to March 2018. Demographic profiles, underlying diseases, and clinical/microbiological outcomes were abstracted retrospectively. During the study period, 73 cases of MRSA bacteremia occurred in children with a median age of 12.4 months. Severe clinical outcomes leading to intensive care unit stay and/or use of mechanical ventilation occurred in 47.5% (35/73); all-cause 30-day mortality was 9.7% (7/72). The median dosage of vancomycin was 40.0 mg/kg/day. There was a weak linear relationship between C trough and the corresponding AUC/MIC (r = 0.235). ROC curves for achieving an AUC/MIC of 300 suggested that the initial C trough at 10 μg/mL could be used as a cut-off value with a sensitivity of 90.5% and a specificity of 44%. Although persistent bacteremia at 48–72 hours after vancomycin administration was observed more frequently when the initial C trough was < 10 μg/mL and initial AUC/MIC was < 300, initial AUC/MIC < 300 was the only risk factor associated with persistent bacteremia at 48–72 hours (adjusted OR 3.05; 95% CI, 1.07–8.68). Initial C trough and AUC/MIC were not associated with 30-day mortality. Although there was a weak relationship between C trough and AUC/MIC, initial AUC/MIC < 300 could be used as a predictor of persistent MRSA bacteremia at 48–72 hours. Further prospective data on optimal vancomycin dosing are necessary to improve clinical and microbiological outcomes in pediatric MRSA bacteremia. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests the standard vancomycin trough goal of 15 to 20 mg/L for serious Staphylococcus aureus infections is associated with acute kidney injury, whereas appropriate monitoring of 24-hour area under the curve (AUC) may decrease nephrotoxicity. As a result, institutions have transitioned to AUC monitoring, the predictive pharmacokinetic/pharmacodynamic parameter of vancomycin to improve safety outcomes. However, this method may require increased pharmacist time and effort. Pharmacist perception of the practice change is largely unknown and warrants investigation. Methods: An electronic survey was disseminated via e-mail to pharmacists 5 months post-AUC implementation. Items of interest were focused on pharmacist perception, including quantity of patients monitored using AUC, justification of the practice change, differences in efficacy and safety, and changes in monitoring time requirements. Results: The pharmacist survey was distributed to 196 pharmacists and 84 responded (43% response rate). Eighty-one pharmacists had monitored patients using AUC methods. Sixty-nine percent of these respondents perceived the change to result in increased or slightly increased patient safety, 27% described no difference, and 4% stated safety was decreased or slightly decreased. Forty-two percent perceived the transition to result in increased or slightly increased efficacy, while 48% noted no difference and 10% responded that efficacy was decreased or slightly decreased. Pharmacists stated the creation of an institutional calculator decreased the time required to calculate AUC. Conclusion: After the change to AUC monitoring, pharmacists perceived improvements in safety outcomes while efficacy was at least similar if not increased. [ABSTRACT FROM AUTHOR]

Introduction: Dalbavancin is a bactericidal lipoglycopeptide active against gram-positives. Its use has been approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI).Methods: We conducted a narrative review of the literature on the safety profile of dalbavancin. The bibliographic research was carried out on the PubMed database on 6 November 2020 by seeking combinations of the following keywords: dalbavancin, adverse effects, safety, drug interactions, and skin infections.Results: Five double-blind Phase 3 randomized clinical trials, 2 open-label randomized trials, and 4 retrospective studies were identified. No statistically significant differences were found between dalbavancin and comparators in the incidence of adverse events. Retrospective studies confirm the low incidence of adverse events.Conclusion: Dalbavancin is a therapeutic option that has demonstrated an excellent safety profile, also in relation to the other MRSA therapies available. Its use represents a cost-effective solution for the treatment of those patients with ABSSSI who would need hospitalization. One limitation of this study is that most of the available data are from Phase III clinical trials. Further real-life studies with a larger sample size are therefore needed to better assess the safety profile of the dalbavancin, especially to investigate the true incidence of rare adverse events. [ABSTRACT FROM AUTHOR]

Background: This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety.Methods: We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).Results: Adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47-0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15-20 μg/mL (OR 2.39, 95% CI 1.78-3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18-0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13-3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28-1.01); however, it was not significant in the analysis of mortality.Conclusions: We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity. [ABSTRACT FROM AUTHOR]