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Background: Cefazolin is guideline recommended for perioperative prophylaxis in orthopedic surgery. Despite its unique R1 side chain, cefazolin is often avoided in patients with beta-lactam allergy with concern for cross reactivity. Objectives: The primary outcome was the percentage of patients who received cefazolin perioperatively. Secondary outcomes included the percentage of patients with a beta-lactam allergy clarified following the telephone interview and clinical outcomes including acute kidney injury, surgical site infection, Clostridioides difficile infection, and re-admission at 30 and 90 days. Methods: This single-center, quasi-experimental study evaluated a pilot program in which a pharmacist phoned patients > 18 years of age with a scheduled orthopedic surgery and a documented beta-lactam allergy to assess their allergy preoperatively. Recommendations to use cefazolin were based on an algorithm. Patients were divided into pre- and post-intervention cohorts. Results: A total of 832 patients were screened for inclusion with 135 and 66 patients included in the pre- and post-intervention cohorts. No significant difference was identified in the primary outcome. In the post-intervention cohort, 62% had a beta-lactam reaction updated in the electronic medical record. Those with a beta-lactam allergy delabeled or made less severe were numerically more likely to receive cefazolin than those with an unchanged reaction or a reaction made more severe (95.2% vs 68% vs 65%). There were no differences in clinical outcomes between groups. Conclusion: A pharmacist-conducted preoperative beta-lactam allergy interview in adult patients undergoing elective orthopedic surgery improved beta-lactam allergy documentation but, did not result in increased utilization of cefazolin., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Wesley D. Kufel has received research grants from Merck and Co. and Melinta Therapeutics and served on the advisory board for Theratechnologies. Jeffrey M. Steele has served on the advisory board for Paratek Pharmaceuticals. All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Free online adaptive vancomycin dosing calculators are available to estimate area under the concentration-time curve (AUC), but the accuracy of predicting vancomycin AUC using these calculators compared with using a 2-point pharmacokinetic approach has not been described., Objective: To evaluate the accuracy of calculator-predicted AUC (cpAUC) using 4 free online calculators compared with reference AUC (rAUC), and to assess pharmacists' impressions of the ease of use., Methods: Vancomycin AUC was estimated using (1) the reference method via the Sawchuk-Zaske method and linear-logarithmic trapezoidal rule using 2 steady-state postdistributional vancomycin serum concentrations and (2) 4 free online vancomycin dosing calculators including ClinCalc, VancoPK, TDMx, and DMC. Accuracy was calculated by dividing cpAUC by rAUC. Ease of cpAUC estimation was determined by using a 10-point Likert scale., Results: All 4 calculators had a median cpAUC accuracy ranging from 89% to 110%. Concordance between cpAUC and rAUC determinations of AUC <400 and > 600 mg·h/L occurred 63.3% to 71.4% and 74.5% to 78.6% of the time, respectively. Pharmacist investigators agreed that ClinCalc and VancoPK calculators were easiest to use., Conclusion and Relevance: cpAUC accuracy varied among the 4 calculators, but all consistently identified patients with an rAUC <400 mg·h/L and an rAUC > 600 mg·h/L at comparable frequencies. All 4 calculators demonstrated some imprecision based on their wide 95% CIs and potential inaccuracies in predicting an rAUC <400 mg·h/L or an rAUC > 600 mg·h/L. Clin Calc and VancoPK were most user friendly based on our pharmacists' impressions.

Background: Compliance with guideline recommendations for surgical antibiotic prophylaxis (SAP) in colorectal surgery, particularly redosing, has been suboptimal at many institutions including ours. This study aimed to evaluate if single-dose antibiotic prophylaxis with ertapenem improves compliance with guideline recommendations for SAP versus multiple-dose antibiotic prophylaxis in elective colorectal surgery. Methods: A retrospective, cohort study of the use of ertapenem compared with standard of care antibiotic agents was performed in adult patients undergoing elective colorectal surgery at an academic medical center between January 2020 and February 2022. The primary outcome was compliance with guideline-recommended SAP for colorectal surgery. The secondary outcome was surgical site infections (SSIs) within 30 days after surgery. Results: A total of 135 patients were included in this study. Fifty-eight patients received single-dose antibiotic prophylaxis with ertapenem and 77 patients received multiple-dose antibiotic prophylaxis. Cefazolin plus metronidazole was the most common multiple-dose regimen (65 of 77). Single-dose antibiotic prophylaxis with ertapenem increased overall SAP compliance (96.6% vs. 64.9%; p < 0.001) as well as compliance with antibiotic administration within the recommended time period before incision (96.6% vs. 84.4%; p = 0.022), compliance with intra-operative antibiotic redosing when warranted (100% vs. 83.1%; p < 0.001), and compliance with guideline-recommended dosing (100% vs. 92.2%; p = 0.037). Surgical site infection rates were not statistically different between the groups (12.1% vs. 19.4%; p = 0.248). Conclusions: Single-dose antibiotic prophylaxis with ertapenem increased compliance with guideline-recommended SAP for elective colorectal surgeries. No statistically significant difference was observed in SSI rates regardless of the antibiotic regimen used.

Introduction: Older adults face a higher risk of vancomycin-related toxicity given their (patho)-physiological changes, making early management of supratherapeutic exposure crucial. Yet, data on vancomycin exposure in older adults is scarce. This study aims to compare vancomycin concentrations between older and younger patients, emphasizing supratherapeutic concentrations and the effect of patient characteristics., Methods: This observational retrospective study was conducted in the University Hospital of Leuven (EC Research S65213). We analyzed early (first) vancomycin concentrations between older (≥ 75 years) and younger patients. Multivariable analyses were conducted to evaluate the association between baseline patient characteristics with supratherapeutic exposure (logistic regression), and dose-normalized concentrations (linear regression)., Results: We included 449 patients aged ≥ 75 years (median 80) and 1609 aged < 75 years (median 61). In univariable analysis, the first-measured vancomycin concentrations were significantly higher in older adults (p < 0.001), who more frequently reached supratherapeutic concentrations (30.7% versus 21%; p < 0.001). In multivariable analysis, factors associated with supratherapeutic concentrations were decreased the estimated glomerular filtration rate calculated by using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR CKD-EPI ) [odds ratio (OR) of 0.98, confidence interval (CI) 0.97-0.98]. Supratherapeutic concentrations had inverse association with giving lower loading dose (OR of 0.59, CI 0.39-0.90), and lower maintenance dose (OR of 0.45, CI 0.26-0.77). Factors that predicted increased dose-normalized concentrations included decreased eGFR CKD-EPI (coefficient of -0.05, CI -0.06 to -0.04), lower body weight (coefficient of -0.04, CI -0.05 to -0.03), increased blood urea nitrogen (coefficient of 0.02, CI 0.01-0.03), and delayed time to therapeutic drug monitoring (TDM) sampling (coefficient of 0.08, CI 0.06-0.09)., Conclusions: The absence of age as a significant factor in the multivariable analysis suggests that eGFR CKD-EPI mediated the relationship between age and vancomycin exposure. Older adults may benefit more from vancomycin TDM., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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.)

Background: Conventionally, vancomycin trough levels have been used for therapeutic drug monitoring (TDM). Owing to the increasing evidence of trough levels being poor surrogates of area under the curve (AUC) and the advent of advanced pharmacokinetics software, a paradigm shift has been made toward AUC-guided dosing. This study aims to evaluate the impact of AUC-guided versus trough-guided TDM on vancomycin-associated nephrotoxicity., Methods: A systematic review was conducted using PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Google scholar, and Cochrane library databases; articles published from January 01, 2009, to January 01, 2021, were retrieved and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Studies that evaluated trough-guided or AUC-guided vancomycin TDM and vancomycin-associated nephrotoxicity were included. Random-effects models were used to compare the differences in nephrotoxicity., Results: Of the 1191 retrieved studies, 57 were included. Most studies included adults and older adults (n = 47, 82.45%). The pooled prevalence of nephrotoxicity was lower in AUC-guided TDM [6.2%; 95% confidence interval (CI): 2.9%-9.5%] than in trough-guided TDM (17.0%; 95% CI: 14.7%-19.2%). Compared with the trough-guided approach, the AUC-guided approach had a lower risk of nephrotoxicity (odds ratio: 0.53; 95% CI: 0.32-0.89). The risk of nephrotoxicity was unaffected by the AUC derivation method. AUC thresholds correlated with nephrotoxicity only within the first 96 hours of therapy., Conclusions: The AUC-guided approach had a lower risk of nephrotoxicity, supporting the updated American Society of Health-System Pharmacists guidelines. Further studies are needed to evaluate the optimal AUC-derivation methods and clinical utility of repeated measurements of the AUC and trough levels of vancomycin., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Objective: This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution., Methods: A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L., Results: Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation ( P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) <400; unchanged regimens had an estimated AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107)., Conclusions: The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

Purpose: The purpose of this study was to (1) determine whether academic medical centers implemented area under the concentration-time curve (AUC)-based monitoring for vancomycin and (2) characterize perceived barriers to implementation and challenges experienced during the implementation process., Methods: A multicenter, cross-sectional electronic survey was distributed to pharmacy representatives from 124 academic medical centers within the Vizient University Health System Consortium Pharmacy Network., Results: Seventy-eight institutions completed the survey, representing a 62.9% response rate. Most institutions were approximately 500-1,000 beds (68/78, 87.2%), and pharmacists were primarily responsible for vancomycin therapeutic drug monitoring (66/78, 84.6%) using pharmacist-driven protocols (57/78, 73.1%). Less than one fourth (18/78, 23.1%) of responding academic medical centers performed AUC-based vancomycin monitoring, and the majority (12/18, 66.7%) used 2-point pharmacokinetics, with a smaller fraction using either Bayesian software or population-based pharmacokinetics. Of the responding institutions that only perform trough-based therapeutic drug monitoring (60/78, 76.9%), most (53/60, 88.3%) did not plan to or were unsure about transitioning to AUC-based monitoring within the next year. Both the most common challenge encountered (13/18, 72.2%) for institutions performing AUC-based monitoring and the most common barrier (44/60, 73.3%) to implementation of this monitoring strategy were pharmacist and/or provider unfamiliarity., Conclusion: The majority of surveyed academic medical centers have not yet implemented AUC-based vancomycin monitoring, and most institutions did not plan to adopt or were unsure about adopting this monitoring strategy within the next year., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Limited evidence exists evaluating pharmacokinetic thresholds for vancomycin efficacy and nephrotoxicity using non-Bayesian methods. The objective of this study was to evaluate the 24-h steady-state vancomycin area under the concentration-time curve (AUC 24 ) thresholds for efficacy and nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus bacteraemia (MRSA-B) after implementing two-point pharmacokinetic therapeutic drug monitoring. A single-centre, retrospective cohort study was performed including adult patients admitted between 1 June 2016 and 1 January 2018 with MRSA-B treated with vancomycin for ≥72 h. The AUC 24 was calculated using peak and trough vancomycin serum concentrations. Clinical success was defined as defervescence and blood culture sterilisation by Day 7. Nephrotoxicity was defined as an increase in serum creatinine of >0.5 mg/dL (or ≥50%) from baseline. Classification and regression tree (CART) analyses were performed to identify AUC 24 thresholds for efficacy and nephrotoxicity. Forty-six patients were included in the study. Clinical success and nephrotoxicity were observed in 81.8% and 13.0%, respectively. The CART-derived vancomycin AUC 24 thresholds for clinical success and nephrotoxicity were ≥297 mg·h/L and ≥710 mg·h/L, respectively. Patients with an AUC 24 ≥297 mg·h/L had a >2.7-fold increase in clinical success compared with those who did not (89.5% vs. 33.3%, respectively; P = 0.01), and patients with an AUC 24 ≥710 mg·h/L had a >7-fold increase in nephrotoxicity compared with those with an AUC 24 <710 mg·h/L (66.7% vs. 9.3%, respectively; P = 0.04). This study supports current recommendations to target vancomycin AUC 24 values of 400-600 mg·h/L when calculated using two-point pharmacokinetics, although a wider range may exist., (Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Objective: Strategies that reduce the time to antimicrobial administration, such as the availability of premix antimicrobials (PMAs) in the emergency department (ED), may better align with the goals of the Surviving Sepsis Campaign and improve outcomes in septic patients. The objective of this study was to evaluate the impact of antimicrobial preparation on time to administration in septic patients located in the emergency department (ED)., Methods: This was a retrospective, single-center, cohort study and adult patients with a diagnosis of sepsis who received at least one initial intravenous (IV) antimicrobial in the ED were included. Time to complete an empiric antimicrobial therapy was defined as the time between prescriber order entry and the infusion initiation time of the final antimicrobial agent of a patient's antimicrobial regimen. Appropriate, empiric antimicrobial therapy was based on treatment recommendations by nationally accepted guidelines for the specific indication., Results: The first antimicrobial was initiated earlier when available as a PMA preparation (median (IQR): premix 25 minutes (16.5-42.3) vs. non-premix 46 minutes (20-102), p=0.027). When comparing complete, empiric antimicrobial regimen administration, there was no difference in time to administration between regimens containing one or more non-premix antimicrobials and regimens containing all PMAs (median (IQR): premix 69 minutes (21-115) vs. non-premix 65 minutes (38.5-133.8); p=0.455)., Conclusions: PMA preparations significantly reduced time to administration of the first antimicrobial agent for septic patients treated in the ED, but time to administration of subsequent antimicrobials were not improved.

Background: Severe sepsis and septic shock represent common presentations in the emergency department (ED) and have high rates of mortality. Guideline-recommended goals of care have been shown to benefit these patients, but can be difficult to provide., Objective: To determine whether the use of a premixed bag consisting of 2 g cefepime and 1 g vancomycin in 1000 mL of normal saline increases the probability of patients receiving Surviving Sepsis Campaign (SSC) recommendations for the initiation of antimicrobials and fluid challenge., Methods: This was a 6-month retrospective analysis conducted to determine the impact of an intervention on time to antimicrobials and fluid administration in patients with severe sepsis and septic shock. Patients presenting to the ED who received a diagnosis of severe sepsis or septic shock and were administered 2 antibiotics were eligible for inclusion. The primary outcome assessed was compliance with SSC recommendations for antibiotic and fluid goals within 3 hours of ED arrival., Results: A total of 160 patients were included. In the intervention group, 63.8% of patients met the primary outcome compared with 22.5% in the historical group (odds ratio = 2.32; 95% CI = 1.67-3.23). Time to administration of antibiotics was less with the combination antibiotic bag (CAB: median (IQR) = 72 (48-115) minutes; non-CAB: median (IQR) = 135 (102-244) minutes; P ≤ 0.001)., Conclusion: This intervention significantly increased the proportion of patients provided with SSC goals of care. Such interventions have not been reported previously and could be meaningful in the management of severe sepsis and septic shock.

Purpose: To determine whether there is an association between higher vancomycin trough concentrations and attainment of a calculated area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ≥400., Methods: A retrospective analysis was conducted among vancomycin-treated adult patients with a positive methicillin-resistant Staphylococcus aureus (MRSA) culture. Attainment of a calculated AUC/MIC ≥400 was compared between patients with troughs in the reference range of 15 to 20 mg/L and those with troughs in the following ranges: <10, 10 to 14.9, and >20 mg/L. Nephrotoxicity was assessed as a secondary outcome based on corrected average vancomycin troughs over 10 days of treatment., Results: Overall, 226 patients were reviewed and 100 included. Relative to troughs ≥10, patients with vancomycin troughs <10 mg/L were 73% less likely to attain an AUC/MIC ≥400 (odds ratio [OR] 0.27, 95% confidence interval [CI]: 0.01-0.75). No difference was found in the attainment of an AUC/MIC ≥400 in patients with troughs of 10 to 14.9 mg/L and >20 mg/L when compared to patients with troughs of 15 to 20 mg/L. The mean corrected average vancomycin trough was higher in patients developing nephrotoxicity compared to those who did not (19.5 vs 14.5 mg/L, P < .001)., Conclusion: Achieving vancomycin serum trough concentrations of 15 to 20 mg/L did not result in an increased attainment of the AUC/MIC target relative to troughs of 10 to 14.9 mg/L but may increase nephrotoxicity risk.

Purpose: In the present narrative review, the authors aimed to discuss the relationship between the pharmacokinetic/pharmacodynamic (PK/PD) of antibiotics and clinical response (including efficacy and toxicity). In addition, this review describes how this relationship can be applied to define the therapeutic range of a particular antibiotic (or antibiotic class) for therapeutic drug monitoring (TDM)., Methods: Relevant clinical studies that examined the relationship between PK/PD of antibiotics and clinical response (efficacy and response) were reviewed. The review (performed for studies published in English up to September 2021) assessed only commonly used antibiotics (or antibiotic classes), including aminoglycosides, beta-lactam antibiotics, daptomycin, fluoroquinolones, glycopeptides (teicoplanin and vancomycin), and linezolid. The best currently available evidence was used to define the therapeutic range for these antibiotics., Results: The therapeutic range associated with maximal clinical efficacy and minimal toxicity is available for commonly used antibiotics, and these values can be implemented when TDM for antibiotics is performed. Additional data are needed to clarify the relationship between PK/PD indices and the development of antibiotic resistance., Conclusions: TDM should only be regarded as a means to achieve the main goal of providing safe and effective antibiotic therapy for all patients. The next critical step is to define exposures that can prevent the development of antibiotic resistance and include these exposures as therapeutic drug monitoring targets., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

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 (AUC PAT ) was evaluated against the reference AUC (AUC REF ) calculated with the log-linear trapezoidal rule using eight measured concentrations, or against AUC (AUC BM-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 AUC PAT /AUC REF 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 (AUC PAT /AUC REF range 0.73-1.30 for 11 h, AUC PAT /AUC REF range 0.62-1.40 for 23 h). In comparison with the evaluated software, AUC PAT was not biased against the AUC BM-P (slope 1.04, intercept -15.80, median AUC PAT /AUC BM-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.

Aims: The 2019 update to the US consensus guideline for vancomycin therapeutic monitoring advocates using Bayesian-guided personalised dosing to maximise efficacy and minimise toxicity of vancomycin. We conducted an observational cohort study of the implementation of bed-side Bayesian-guided vancomycin dosing in vascular surgery patients., Methods: Over a 9-month prospective study period, vascular surgery patients were dosed vancomycin using Bayesian-guided dosing decision tool (DoseMeRx) and compared retrospectively with a control group admitted to the same ward in the 14 months prior to the study and dosed using a standard algorithmic approach. Primary endpoints were proportion of patients achieving mean area under the curve in 24 hours (AUC 24 ) in the acceptable range 350-450 mg/L• h and percentage time in acceptable range (%TTR). Secondary endpoints focused on clinical outcomes including incidence of acute kidney injury., Results: A significantly higher proportion of DoseMeRx patients achieved mean AUC 24 values in the acceptable range compared to the control group; 71/104 (68.3%) vs 58/139 (41.7%), P < .005. The median %TTR was also greater in DoseMeRx patients compared to the control group (57.1 vs 30.0%, P < .00001). Patients in the DoseMeRx group missed an average of 0.23 doses per course compared to 1.04 doses in the control group (P < .00001). No difference was observed in secondary (clinical) outcomes between the 2 groups., Conclusion: Bedside Bayesian-guided personalised dosing of vancomycin increases the proportion of patients achieving target AUC 24 and the %TTR., (© 2020 The British Pharmacological Society.)

Published vancomycin dosing recommendations for patients receiving maintenance hemodialysis were not designed to meet newly recommended 24-hour area under the curve/minimum inhibitory concentration (AUC 24h /MIC) pharmacokinetic/pharmacodynamic targets. The aims of this study were to predict pharmacokinetic/pharmacodynamic target attainment rates with a commonly used vancomycin regimen and to design a new dosing scheme incorporating therapeutic drug monitoring (TDM) to maximize target attainment in patients receiving vancomycin and hemodialysis with high- or low-flux hemodialyzers. Vancomycin pharmacokinetic- and dialysis-specific parameters were incorporated into Monte Carlo simulations (MCS). A commonly used vancomycin regimen was modeled to determine its likelihood of attaining AUC 24h /MIC targets for 1 week of thrice-weekly hemodialysis treatments. MCS was then used to develop optimal initial vancomycin dosing for patients receiving intradialytic or postdialytic vancomycin administration with either high- or low-flux hemodialyzers. Finally, a new MCS model incorporating TDM was built to further optimize the probability of pharmacokinetic/pharmacodynamic target attainment. Traditional vancomycin dosing methods are unlikely to meet AUC 24h /MIC targets. Vancomycin doses necessary to attain AUC 24h /MIC targets are significantly influenced by hemodialyzer permeability and whether vancomycin is administered intradialytically or after hemodialysis. Depending on dialyzer type and whether vancomycin is administered during or after hemodialysis, loading doses of 25 to 35 mg/kg followed by maintenance doses of 7.5 to 15 mg/kg are necessary to reach minimum AUC 24h /MIC targets in 90% of virtual patients. For a 3-day interdialytic period, a 30% higher maintenance dose is required to maintain target attainment. Dosing based on a single vancomycin serum concentration obtained prior to the second dialysis session greatly enhances the probability of target attainment., (© 2020, The American College of Clinical Pharmacology.)

What Is Known and Objective: The influence of venovenous extracorporeal membrane oxygenation (VV-ECMO) on the population pharmacokinetics (PPK) of vancomycin in recipients after lung transplantation (LTx) is unknown. We investigated whether VV-ECMO influences vancomycin PPK and determined optimal recommended dosage for patients after LTx., Methods: We tested vancomycin serum concentration and calculated PPK parameters using NONMEM. To check for any potential influence of ECMO on vancomycin PK, we compared ECMO patients with a non-ECMO patient control group, and patients before and after ECMO weaning as self-control to analysed changes in vancomycin PK. Monte Carlo dosing simulation was conducted to explore vancomycin dosing regimens., Results: Nineteen ECMO and 6 non-ECMO lung transplant recipients were enrolled. Vancomycin serum concentrations did not significantly differ between patients with and without ECMO support. Comparison of separate vancomycin population pharmacokinetic models showed that ECMO patients had smaller peripheral compartment volume of distribution (V 2 ) [Estimate (relative standard error, RSE, %) 19.7 (12) vs. 22 (17) L, P = .003] than non-ECMO patients. For treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC ≤ 0.5 µg/mL, venous infusion of 400 mg vancomycin every 8 hours was recommended. For MRSA infection with MIC ≤ 1 µg/mL, the proposed dosage was 600 mg every 8 hours., What Is New and Conclusion: Venovenous extracorporeal membrane oxygenation slightly alters vancomycin PK but does not significantly impact vancomycin serum concentration in patients after LTx. Dose adjustment is not necessary for VV-ECMO support. Specific vancomycin dosing regimens with lower nephrotoxicity may benefit LTx recipients with VV-ECMO., (© 2020 John Wiley & Sons Ltd.)

Background: Dalbavancin, albeit indicated for the treatment of skin structure infections, is used for a much wider range of infections. This drug is characterized by a long half-life (more than 200 hours), a favorable safety profile, and an activity against a wide array of gram-positive organisms, including several strains of Staphylococci and Enterococci., Methods: In this study, we presented 3 cases of critically ill patients treated with dalbavancin. All patients were therapeutically monitored for plasma dalbavancin concentrations; ultrafiltrate dalbavancin concentrations were assessed in a patient undergoing continuous renal-replacement therapy. Dalbavancin concentrations were measured using a validated liquid chromatographic method coupled with mass spectrometry., Results: All 3 severely ill patients experiencing necrotizing fasciitis were successfully treated during the acute phase with dalbavancin. Dalbavancin clearance in patient 3 (0.334 L/h) was considerably increased compared with values measured in the other 2 patients (0.054 and 0.075 L/h) and with data reported in the literature (0.04-0.06 L/h)., Conclusions: Our case reports presented preliminary evidence that dalbavancin can be considered a therapeutic option for necrotizing fasciitis in intensive care unit patients. The role of hypoalbuminemia during dalbavancin exposure merits further investigation.

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the epidemiology, diagnosis, prevention, and management of methicillin-resistant Staphylococcus aureus (MRSA) infections in solid organ transplantation. Despite an increasing armamentarium of antimicrobials active against MRSA, improved diagnostic tools, and overall declining rates of infection, MRSA infections remain a substantial cause of morbidity and mortality in solid organ transplant recipients. Pre- and post-transplant MRSA colonization is a significant risk factor for post-transplant MRSA infection. The preferred initial treatment of MRSA bacteremia remains vancomycin. Hand hygiene, chlorhexidine bathing in the ICU, central-line bundles that focus on reducing unnecessary catheter use, disinfection of patient equipment, and the environment along with antimicrobial stewardship are all aspects of an infection prevention approach to prevent MRSA transmission and decrease healthcare-associated infections., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)