Vancomycin Monitoring Research Articles

The Impact of Pharmacist Led Vancomycin Order Set Implementation in a Computerized-Prescriber-Order-Entry (CPOE) System at a Tertiary Care Centre: A Quasi Experimental Study

Introduction: Our hospital has developed a vancomycin protocol in order to improve vancomycin dosing and prevent improper sampling time of vancomycin levels and treatment failure. The study objective is to evaluate the impact of implementing a vancomycin order set integrated into a Computerized-Prescriber-Order-Entry (CPOE) system by pharmacist in adult surgical wards to optimize vancomycin dosing and monitoring. Primary objective: Evaluation of the correct sampling time of vancomycin trough levels by implementing a vancomycin order set guiding nurses and physicians on the appropriate sampling time. Secondary objectives: Evaluation of the impact of vancomycin order set integrated into CPOE system on vancomycin initial doses, appropriate use based on indication and time to reach target therapeutic level. Method: This study was a prospective quasi-experimental study. Patients who are >18 years, admitted to surgical wards, receiving new vancomycin orders, creatinine clearance ≥15 ml/min and weighing 40-120 kg were eligible. We excluded patients receiving vancomycin loading doses, prophylaxis, treatment course <5 days and random or peak vancomycin levels. Educational sessions were provided to the surgical residents on the use the order set by pharmacy resident, subsequently vancomycin orders were then reassessed after the order set implementation. Results: Total of 272 vancomycin trough levels were collected (136 levels in the pre-phase and 136 levels in the post-implementation phase) from 33 patients who met the study eligibility criteria. A 10% reduction in inappropriate vancomycin trough levels in the post-implementation phase was observed compared to the pre-phase (p=0.478) Appropriate vancomycin initial doses for the study patients were 2 out of 11 doses (18%) in the pre-phase and 22 doses in the post-phase (50%) (p=0.078). Conclusion: The implementation of an institutional vancomycin order set did not result in a significant change in appropriate vancomycin initial dosing and trough level sampling time in the adult surgical wards in our hospital.

Therapeutic Drug Monitoring of Vancomycin in Dermal Interstitial Fluid Using Dissolving Microneedles.

Objective: To design an alternative painless method for vancomycin (VCM) monitoring by withdrawing interstitial fluid (ISF) the skin using dissolving microneedles (DMNs) and possibly replace the conventional clinical blood sampling method.Methods: Male Wistar rats were anesthetized with 50 mg/kg sodium pentobarbital. Vancomycin at 5 mg/mL in saline was intravenously administered via the jugular vein. ISF was collected from a formed pore at 15, 30, 45, 60, 75, 90, and 120 min after the DMNs was removed from the skin. In addition, 0.3 mL blood samples were collected from the left femoral vein.Results: The correlation between the plasma and ISF VCM concentrations was significantly strong (r = 0.676, p < 0.05). Microscopic observation of the skin after application of the DMNs demonstrated their safety as a device for sampling ISF.Conclusion: A novel monitoring method for VCM was developed to painlessly determine concentrations in the ISF as opposed to blood sampling.

Audit of vancomycin and gentamicin dosing and monitoring in Connolly Hospital Blanchardstown (CHB) 2014

Background The dosing of vancomycin and gentamicin relies largely on the weight and renal function of a patient. Due to their narrow therapeutic index, these drugs also require therapeutic drug monitoring (TDM) during treatment to ensure efficacy, reduce potential for otoand nephrotoxicity, and reduce potential for resistance. Guidelines for the use of vancomycin and gentamicin, as well as a dosing calculator, is in place in CHB. This audit was performed around the appropriate prescribing and monitoring of these two antibiotics in CHB and findings were compared to similar audits carried out in 2010 and 2012.

Pharmacist-led implementation of a vancomycin guideline across medical and surgical units: impact on clinical behavior and therapeutic drug monitoring outcomes.

BackgroundVancomycin is the antibiotic of choice for the treatment of serious infections such as methicillin-resistant Staphylococcus aureus (MRSA). Inappropriate prescribing of vancomycin can lead to therapeutic failure, antibiotic resistance, and drug toxicity.ObjectiveTo examine the effectiveness of pharmacist-led implementation of a clinical practice guideline for vancomycin dosing and monitoring in a teaching hospital.MethodsAn observational pre–post study design was undertaken to evaluate the implementation of the vancomycin guideline. The implementation strategy principally involved education, clinical vignettes, and provision of pocket guidelines to accompany release of the guideline to the hospital Intranet. The target cohort for clinical behavioral change was junior medical officers, as they perform the majority of prescribing and monitoring of vancomycin in hospitals. Assessment measures were recorded for vancomycin prescribing, therapeutic drug monitoring, and patient outcomes.ResultsNinety-nine patients, 53 pre- and 46 post-implementation, were included in the study. Prescribing of a loading dose increased from 9% to 28% (P=0.02), and guideline adherence to starting maintenance dosing increased from 53% to 63% (P=0.32). Dose adjustment by doctors when blood concentrations were outside target increased from 53% to 71% (P=0.12), and correct timing of initial concentration measurement increased from 43% to 57% (P=0.23). Appropriately timed trough concentrations improved from 73% to 81% (P=0.08). Pre-dose (trough) concentrations in target range rose from 33% to 44% (P=0.10), while potentially toxic concentrations decreased from 32% to 21% (P=0.05) post-implementation. Infection cure rates for patients increased from 85% to 96% (P=0.11) after the guideline was implemented.ConclusionThe implementation strategy employed in this study demonstrated potential effectiveness, and should prompt additional larger studies to optimize strategies that will translate into improved clinical practice using vancomycin.

What are the current guidelines and rationale for vancomycin monitoring?

Vancomycin is an antibiotic that can be challenging from a therapeutic and monitoring standpoint. Guidelines suggest certain situations where monitoring is encouraged; this article outlines those situations.

The ADMIN-ICU survey: a survey on antimicrobial dosing and monitoring in ICUs

There is little evidence and few guidelines to inform the most appropriate dosing and monitoring for antimicrobials in the ICU. We aimed to survey current practices around the world. An online structured questionnaire was developed and sent by e-mail to obtain information on local antimicrobial prescribing practices for glycopeptides, piperacillin/tazobactam, carbapenems, aminoglycosides and colistin. A total of 402 professionals from 328 hospitals in 53 countries responded, of whom 78% were specialists in intensive care medicine (41% intensive care, 30% anaesthesiology, 14% internal medicine) and 12% were pharmacists. Vancomycin was used as a continuous infusion in 31% of units at a median (IQR) daily dose of 25 (25-30) mg/kg. Piperacillin/tazobactam was used as an extended infusion by 22% and as a continuous infusion by 7%. An extended infusion of carbapenem (meropenem or imipenem) was used by 27% and a continuous infusion by 5%. Colistin was used at a daily dose of 7.5 (3.9-9) million IU (MIU)/day, predominantly as a short infusion. The most commonly used aminoglycosides were gentamicin (55%) followed by amikacin (40%), with administration as a single daily dose reported in 94% of the cases. Gentamicin was used at a daily dose of 5 (5-6) mg/day and amikacin at a daily dose of 15 (15-20) mg/day. Therapeutic drug monitoring of vancomycin, piperacillin/tazobactam and meropenem was used by 74%, 1% and 2% of the respondents, respectively. Peak aminoglycoside concentrations were sampled daily by 28% and trough concentrations in all patients by 61% of the respondents. We found wide variability in reported practices for antibiotic dosing and monitoring. Research is required to develop evidence-based guidelines to standardize practices.

Influence of systemic inflammatory response syndrome on the pharmacokinetics of vancomycin

Therapeutic drug monitoring (TDM) of vancomycin (VCM) is recommended to minimize its nephrotoxicity and maximize efficacy. Recently, the concept of systemic inflammatory response syndrome (SIRS) has been introduced to describe a clinical state resulting from the actions of complex intrinsic mediators in an acute-phase systemic response. However, there are few reports on the pharmacokinetics of VCM in patients with SIRS. This study investigated the effect of SIRS on the pharmacokinetics of VCM by analyzing the predictability of TDM and pharmacokinetic parameters in 31 non-SIRS patients and 52 SIRS patients, with stratification by SIRS score. The mean prediction error (ME) and mean absolute prediction error in SIRS score 2 and 3 patients differed from those in non-SIRS patients. The ME in the score 4 group showed a negative value. In the comparison of pharmacokinetic parameters by SIRS score, a significantly lower CL(vcm) value was observed at score 4 compared with scores 2 and 3, a higher Vd value was observed at score 4 compared with non-SIRS and at score 3, and a longer T1/2 was observed at score 2. In the comparison of patient characteristics by SIRS score, albumin, aspartate aminotransferase, and alanine aminotransferase levels showed differences among the scores. However, no correlation was observed between VCM pharmacokinetics and these three laboratory parameters. These findings suggest that the pharmacokinetics of VCM may be affected by the pathology of SIRS rather than by patient characteristics.

Balancing vancomycin efficacy and nephrotoxicity: should we be aiming for trough or AUC/MIC?

Sixty years later, the question that still remains is how to appropriately utilize vancomycin in the pediatric population. The Infectious Diseases Society of America published guidelines in 2011 that provide guidance for dosing and monitoring of vancomycin in adults and pediatrics. However, goal vancomycin trough concentrations of 15-20μg/mL for invasive infections caused by methicillin-resistant Staphylococcus aureus were based primarily on adult pharmacokinetic and pharmacodynamic data that achieved an area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of ≥400. Recent pediatric literature shows that vancomycin trough concentrations needed to achieve the target AUC/MIC are different than the adult goal troughs cited in the guidelines. This paper addresses several thoughts, including the role of vancomycin AUC/MIC in dosing strategies and safety monitoring, consistency in laboratory reporting, and future directions for calculating AUC/MIC in pediatrics.

Appropriate vancomycin use in a Malaysian tertiary hospital based on current HICPAC recommendations.

Antibiotic resistance is a rapidly emerging problem. A major concern is methicillin-resistant Staphylococcus aureus (MRSA), especially in developing countries where cost-effectiveness is imperative. Restriction of vancomycin usage is necessary to reduce the emergence of vancomycin-resistant organisms. The aim of this study was to look into the appropriate use of vancomycin based on the Healthcare Infection Control Practices Advisory Committee (HICPAC) guidelines and to investigate serum levels of vancomycin. The study was performed retrospectively. Medical records of patients treated with vancomycin for the past year were identified and selected. Overall, 118 patients were treated with vancomycin. Appropriate use of vancomycin was significantly higher than inappropriate use (p = 0.001). Approximately 85% (n = 100) of patients were given vancomycin for treatment, whereas the rest were given it for prophylaxis. Appropriate use of vancomycin was observed in 67% (n = 79) of patients. However, there was still a high rate of inappropriate vancomycin use for prophylaxis and treatment (n = 39, 33.1%). The most common reason for inappropriate use was non-neutropenic and non-line related sepsis (n = 36, 30.8%). Therapeutic drug monitoring of vancomycin was performed in 79 patients (67%). Most patients (n = 53, 67%) demonstrated sub-therapeutic levels during the first measurement. There was no significant difference between trough levels achieved with a higher (> 15 mg/kg) versus a lower dose (< 15 mg/kg). This study demonstrates that there was still a high level of inappropriate vancomycin use, which could potentially contribute to vancomycin resistance.

Monitoring of Outpatient Parenteral Antimicrobial Therapy and Implementation of Clinical Pharmacy Services at a Community Hospital Infusion Unit

Background: In 2004, the Infectious Diseases Society of America (IDSA) published monitoring guidelines for outpatient parenteral antimicrobial therapy (OPAT), but no assessment of their utilization has been reported. We evaluated adherence to these recommendations by physicians at infusion centers and then piloted a program of supervision of monitoring by pharmacists. Methods: Phase I: We performed a retrospective case–control study of patients who received OPAT over 1 year at 2 hospital infusion centers. Controls were patients treated by an infectious diseases (ID) physician, and cases were those without an ID physician. Patients were excluded if they received fewer than 3 days of OPAT. Clinical pharmacy monitoring services were then implemented for patients on OPAT prescribed by non-ID physicians at 1 hospital’s infusion unit. Two outcomes were measured: adherence to guidelines on monitoring and attainment of goal vancomycin and aminoglycoside serum concentrations when appropriate. The results for non-ID physicians were compared to both ID physicians and subsequently a pharmacist. Results: Ninety-nine patients were included in the retrospective study. Compared with patients who had ID physician supervision, the non-ID physicians who prescribed OPAT for 39 patients had lower adherence to monitoring recommendations (35.9% vs 68.3%, P = .003). No difference could be detected in achievement of goal vancomycin and aminoglycoside serum concentrations for the 14 cases and 19 controls requiring therapeutic drug monitoring (57.1% vs 68.4%, respectively, P = .765). Seven patients were enrolled in the study after pharmacy monitoring was implemented. Adherence to monitoring recommendations for these patients was significantly improved compared to the prior patients who lacked ID physician supervision (35.9% vs 100%, P = .0065). Conclusion: Non-ID physicians are less likely to monitor OPAT according to the IDSA guidelines than ID physicians; however, pharmacist oversight improves adherence to recommendations. Further studies of monitoring of OPAT by pharmacists should investigate the impact of pharmacist involvement on prevention of adverse events and hospital readmissions.

Vancomycin monitoring in children using bayesian estimation.

Optimal monitoring of vancomycin in children needs evaluation using the exposure target with area under the curve (AUC) of the serum concentrations versus time over 24 hours. Our study objectives were to: (1) compare the accuracy and precision of vancomycin AUC estimations using 2 sampling strategies-1 serum concentration sample (1S, near trough) versus 2 samples (2S, near peak and trough) against the rich sample (RS) method; and (2) determine the performance of these strategies in predicting future AUC against an internal validation sample (VS). This was a retrospective cohort study using population-based pharmacokinetic modeling with Bayesian post hoc individual estimations in nonlinear mixed effects modeling (version 7.2). Pediatric subjects 3 months-21 years of age who received vancomycin ≥48 hours and had more than 3 drug samples within the first ≤96 hours of therapy were enrolled. Outcome measures were the accuracy, precision, and internal predictive performance of AUC estimations using 2 monitoring strategies (ie, 1S versus 2S) against the RS (which was derived from modeling all serum vancomycin concentrations obtained anytime during therapy) and VS (from serum concentrations obtained after 96 hours of therapy). Analysis included 138 subjects with 712 vancomycin serum concentrations. Median age was 6.1 (interquartile range, 2.2-12.2) years, weight 22 (13-38) kg, and baseline serum creatinine 0.37 (0.30-0.50) mg/dL. Both accuracy and precision were improved with the 2S, compared with 1S, for AUC estimations (-2.0% versus -7.6% and 10.3% versus 12.8%, respectively) against the RS. Improved accuracy and precision were also observed for 2S when evaluated against VS in predicting future AUC. Compared with 1S, the 2S sampling strategy for vancomycin monitoring improved accuracy and precision in estimating and predicting future AUC. Evaluating 2 drug concentrations in children may be prudent to ensure adequate drug exposure.

Therapeutic monitoring of intravenous vancomycin in a pediatric critical care unit

In critically ill pediatric patients vancomycin distribution and elimination is altered underscoring the need for pharmacokinetic monitoring; however the therapeutic trough ranges have not been validated for children. To describe the pharmacokinetics of intravenous vancomycin in critically ill pediatric patients using plasmatic vancomycin monitoring. Retrospective, descriptive study performed in a paediatric critical care unit. Vancomycin serum levels (Cmin and Cpeak), t ½ and Vd were determined in 1 month to 12 year old patients receiving ≥ 40 mg per-kg-per day. Plasmatic levels were measured at therapy onset and during follow up, evaluating the proportion of trough level determinations within therapeutic range, the average trough concentration, and the Cpeak achieved. A total of 65 plasmatic vancomycin monitorings were analysed in 45 patients. The average values for Ctrough, Cpeak, t1/2 and Vd were 10.4 μg/mL, 22.7 μg/mL, 3,1 h and 0.7 L/kg, respectively. An average dose of 47,1 mg/kg/day achieved initial Ctrough levels < 10 mg/mL in 60% of patients (n = 27), between 10 and 14,9 μg/mL in 22,2% (n = 10), between 15 to 20 μg/mL in 4% (n: 2), and > 20 μg/mL in 13,3% (n: 6). Vancomycin doses of 40 mg/kg/day are insufficient for critically ill paediatric patients without renal failure. A higher starting dose and monitoring of plasma levels must be considered in this population.

PKP-008 Assessment of the effectiveness of monitoring vancomycin in patients undergoing haemodialysis

BackgroundVancomycin is an antibiotic against Gram positive bacteria. Vancomycin is useful in treating infections caused by foreign materials, such as catheters used in haemodialysis. It is eliminated mainly through the...

CP-075 MDRD and CKD-EPI equations versus Cockroft-Gaultin in dose optimisation

BackgroundThe Cockroft-Gault (CG) equation has been commonly used to estimate glomerular filtration rate (GFR) and optimise the dose of medicines. Currently, many laboratories have incorporated the Modification of Diet in...

Questioning the accuracy of trough concentrations as surrogates for area under the curve in determining vancomycin safety.

Questioning the accuracy of trough concentrations as surrogates for area under the curve in determining vancomycin safety.

Underestimation of the Calculated Area Under the Concentration-Time Curve Based on Serum Creatinine for Vancomycin Dosing

BackgroundThe ratio of the steady-state 24-hour area under the concentration-time curve (ssAUC24) to the MIC (AUC24/MIC) for vancomycin has been recommended as the preferred pharmacodynamic index. The aim of this study was to assess whether the calculated AUC24 (cAUC24) using the creatinine clearance (CLcr) differs from the ssAUC24 based on the individual pharmacokinetic data estimated by a commercial software.Materials and MethodsThe cAUC24 was compared with the ssAUC24 with respect to age, body mass index, and trough concentration of vancomycin and the results were expressed as median and interquartile ranges. A correlation between the cAUC24 and ssAUC24 and the trough concentration of vancomycin was evaluated. The probability of reaching an AUC24/MIC of 400 or higher was compared between the cAUC24 and ssAUC24 for different MICs of vancomycin and different daily doses by simulation in a subgroup with a trough concentration of 10 mg/L and higher.ResultsThe cAUC24 was significantly lower than the ssAUC24 (392.38 vs. 418.32 mg·hr/L, P < 0.0001) and correlated weakly with the trough concentration (r = 0.649 vs. r = 0.964). Assuming a MIC of 1.0 mg/L, the probability of reaching the value of 400 or higher was 77.5% for the cAUC24/MIC and 100% for the ssAUC24/MIC in patients with a trough concentration of 10 mg/L and higher. If the MIC increased to 2.0 mg/L, the probability was 57.7% for the cAUC24/MIC and 71.8% for the ssAUC24/MIC at a daily vancomycin dose of 4,000 mg.ConclusionsThe cAUC24 using the calculated CLcr is usually underestimated compared with the ssAUC24 based on individual pharmacokinetic data. Therefore, to obtain a more accurate AUC24, therapeutic monitoring of vancomycin rather than a simple calculation based on the CLcr should be performed, and a more accurate biomarker for renal function is needed.

Assessment of Therapeutic Drug Monitoring of Vancomycin in Elderly Patients According to New Guidelines

BackgroundConcerns regarding increasing microbial resistance to vancomycin have resulted in recommendations for a higher trough serum vancomycin concentration. This study aimed to assess the dosage guidelines targeting vancomycin trough concentrations of 15-20 mg/L.MethodsAbout 216 adult patients (age, >60 yr) were treated with intravenous vancomycin. The patients were divided into 2 groups according to their target vancomycin trough concentrations: the previous guideline group (n=108) treated with targeted vancomycin trough concentrations of 5-15 mg/L from Jan 2009 through April 2011 and the new guideline group (n=108) treated with targeted concentrations of 15-20 mg/L from November 2011 through July 2012.ResultsThe 2 groups were not significantly different with respect to age, weight, initial serum creatinine, initial creatinine clearance, predictive trough levels, doses, serum drug concentrations, and area under the curve/minimal inhibitory concentrations. Regarding the proportions of vancomycin trough concentrations, the target range was achieved in 50% in the previous guideline group and in 16% in the new guideline group. In the previous and new guideline groups, the trough concentrations of 10-20 mg/dL were observed in 32.4% and 52.8% patients, respectively, and those of <10 mg/L were observed in 45.4% and 29.6%, respectively.ConclusionsCompared to the previous guideline group, the new guideline group showed higher proportions in the therapeutic range of 10-20 mg/L and lower proportions in trough concentrations <10 mg/L. The strictly managed vancomycin therapeutic drug monitoring in the new guideline group was assessed as more effective.

Farmacocinética de vancomicina en niños hospitalizados en una unidad de paciente crítico

Monitoring PK/PD of vancomycin with basal and peak serum levels and the area under the curve of drug exposure 24 h/MIC (ABC 24 h/MIC) could optimize the management of children. To study the PK of vancomycin in children hospitalized in the Pediatric Intensive Care Unit (PICU), assessing PK/PD parameters withABC24 h/MIC. Retrospective, descriptive study in the PICU (Hospital Luis Calvo Mackenna) between January 2008-March 2010. We included children < 18 years who required antimicrobial treatment with vancomycin for suspected/confirmed staphylococcal infection using a dose of 40 mg/k/day. Plasmatic levels were performed one hour postinfusion and 30 min prior to the next dose. The following PK/PD parameters were calculated: vancomycin clearance, elimination rate constant, volume of distribution, half-life (T1/2) and ABC 24 h/ MIC. We enrolled eighty-four children. According to ABC 24 h/MIC obtained, 54% (45/84) of children reached an optimal level (> 400 mg*hr/L). Based on the traditional PK/PD parameters, 49% of cases (41/84) presented a basal level of vancomycin in the therapeutic range (5-15 μg/mL) and of those, only 39% (16/41) had a ABC 24 h/MIC over 400 mg*h/L. Based on our results, children admitted to PICU could be exposed to sub therapeutic doses of vancomycin. We recommend to implement tailored antimicrobial treatment monitoring vancomycin PK/PD parameters.

Benefits of therapeutic drug monitoring of vancomycin: a systematic review and meta-analysis.

Background and ObjectiveThe necessity of therapeutic drug monitoring (TDM) for vancomycin is controversial. The objective of the current review was to evaluate the available evidence for the necessity of TDM in patients given vancomycin to treat Gram-positive infections.MethodsMedline, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were searched. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM groups vs. non-TDM groups were included. Two reviewers independently extracted the data. The primary outcome was clinical efficacy of therapy. Secondary outcomes included vancomycin associated nephrotoxicity, duration of vancomycin therapy, length of hospital stay, and mortality. Meta-analysis was performed using the Mantel-Haenszel fixed effect method (FEM). Odds ratios (ORs) or weighted mean differences (WMD) with 95% confidence intervals (95%CIs) were calculated for categorical and continuous outcomes, respectively.ResultsOne randomized controlled trial (RCT) and five cohort studies were included in the meta-analysis. Compared with non-TDM groups, TDM groups had significantly higher rates of clinical efficacy (OR = 2.62, 95%CI 1.34–5.11 P = 0.005) and decreased rates of nephrotoxicity (OR = 0.25, 95%CI 0.13–0.48 P<0.0001). Subgroup analyses showed that TDM group had significantly higher rates of clinical efficacy in both cohort studies subgroup (OR = 3.04, 95%CI 1.34–6.90) and in Asian population subgroup (OR = 3.04, 95%CI 1.34–6.90). TDM group had significantly decreased rates of nephrotoxicity in all subgroup. There was no significant difference in duration of vancomycin therapy (WMD = −0.40, 95%CI −2.83–2.02 P = 0.74) or length of stay (WMD = −1.01, 95%CI −7.51-5.49 P = 0.76) between TDM and non-TDM groups. Subgroup analyses showed there were no differences in duration of vancomycin therapy. Only one study reported mortality rates.ConclusionsStudies to date show that TDM significantly increases the rate of clinical efficacy and decreases the rate of nephrotoxicity in patients treated with vancomycin.

Augmented Renal Clearance of Vancomycin and Levetiracetam in a Traumatic Brain Injury Patient

Increased creatinine clearance and subsequent elevated antimicrobial clearance is evident in many traumatic brain injury (TBI) patients due to augmented renal clearance (ARC). Little is known about the effects of ARC on other renally-eliminated medications, such as the anti-epileptic drug levetiracetam. This is a case report of serum monitoring of vancomycin and levetiracetam in a 22 year old female with ARC after severe TBI. The patient exhibited ARC of vancomycin as evidenced by her low serum concentrations with standard vancomycin dosing. Her estimated creatinine clearance based on vancomycin clearance was 243.9ml/min. Serum concentrations also suggested ARC of levetiracetam. No toxicities for either medication were noted, even after dose adjustment to account for possible ARC. Vancomycin and levetiracetam both appear to be subject to ARC after TBI. Clinicians should be mindful that standard dosing of these agents may not achieve typical target concentrations in this clinical scenario.