Duration Of Vancomycin Therapy Research Articles

Vancomycin associated acute kidney injury in patients with infectious endocarditis: a large retrospective cohort study.

Background: Vancomycin remains the cornerstone antibiotic for the treatment of infective endocarditis (IE). Vancomycin has been associated with significant nephrotoxicity. However, vancomycin associated acute kidney injury (AKI) has not been evaluated in patients with IE. We conducted this large retrospective cohort study to reveal the incidence, risk factors, and prognosis of vancomycin-associated acute kidney injury (VA-AKI) in patients with IE. Methods: Adult patients diagnosed with IE and receiving vancomycin were included. The primary outcome was VA-AKI. Results: In total, 435 of the 600 patients were enrolled. Of these, 73.6% were male, and the median age was 52 years. The incidence of VA-AKI was 17.01% (74). Only 37.2% (162) of the patients received therapeutic monitoring of vancomycin, and 30 (18.5%) patients had reached the target vancomycin trough concentration. Multiple logistic regression analysis revealed that body mass index [odds ratio (OR) 1.088, 95% CI 1.004, 1.179], duration of vancomycin therapy (OR 1.030, 95% CI 1.003, 1.058), preexisting chronic kidney disease (OR 2.291, 95% CI 1.018, 5.516), admission to the intensive care unit (OR 2.291, 95% CI 1.289, 3.963) and concomitant radiocontrast agents (OR 2.085, 95% CI 1.093, 3.978) were independent risk factors for VA-AKI. Vancomycin variety (Lai Kexin vs. Wen Kexin, OR 0.498, 95% CI 0.281, 0.885) were determined to be an independent protective factor for VI-AKI. Receiver operator characteristic curve analysis revealed that duration of therapy longer than 10.75 days was associated with a significantly increased risk of VA-AKI (HR 1.927). Kidney function was fully or partially recovered in 73.0% (54) of patients with VA-AKI. Conclusion: The incidence of VA-AKI in patients with IE was slightly higher than in general adult patients. Concomitant contrast agents were the most alarmingly nephrotoxic in patients with IE, adding a 2-fold risk of VA-AKI. In patients with IE, a course of vancomycin therapy longer than 10.75 days was associated with a significantly increased risk of AKI. Thus, closer monitoring of kidney function and vancomycin trough concentrations was recommended in patients with concurrent contrast or courses of vancomycin longer than 10.75 days.

193. Rapid Diagnostic Testing and Vancomycin Utilization for Contaminated Blood Cultures

Abstract Background Bacteremia is a prevalent hospital acquired infection that affects nearly one in ten hospitalized patients. Rates of contaminated blood cultures have ranged from 0.6% to 6% in the literature. Vancomycin is often chosen as empiric coverage for gram positive organisms while awaiting bacterial identification. The purpose of this study was to evaluate the impact of GenMark ePlex Blood Culture Identification Panel (BCID) implementation on the duration of vancomycin therapy for blood cultures contaminated with coagulase negative staphylococci (CoNS). Methods A retrospective chart review was conducted on patients meeting inclusion criteria during a six month period prior to BCID implementation and post BCID implementation, from 03/01/2019 to 08/31/2019 and 03/01/2021 to 08/31/2021. The primary outcome analyzed was the duration of vancomycin therapy, in hours, in patients with a contaminated blood culture. Contaminated blood cultures was defined as a single blood culture growing CoNS. Secondary outcomes included hospital length of stay, readmission for treatment of contaminated blood cultures, and nephrotoxicity. Results This IRB-approved study included 190 patients, 75 in the pre-BCID group and 115 in the post-BCID group. The average duration of vancomycin therapy was 53.7 hours in the pre-BCID group and 20.5 hours in the post-BCID group (p = 0.04). Time to organism identification was reduced from 22.8 hours in the pre-BCID group to 12 hours in the post-BCID group (p = 0.5). Additionally, our study did not find a difference in nephrotoxicity, hospital length of stay, or readmissions between the two groups. Conclusion Following implementation of the GenMark ePlex Blood Culture Identification Panel (BCID), there was a reduction in both duration of vancomycin therapy and time to culture identification for blood cultures contaminated with CoNS. Rapid diagnostic testing is helpful in clinical decision-making and can lead to earlier discontinuation of empiric antibiotics, such as vancomycin. Disclosures All Authors: No reported disclosures.

1287: METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS NARES SCREEN LEADS TO VANCOMYCIN DE-ESCALATION IN TRAUMA

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nares swab is a proven screening tool to de-escalate vancomycin therapy due to its high negative predictive value in pneumonia and other infections. However, data are lacking on the utility of this test in the critically ill trauma population, which is at high risk for hospital-acquired infections. This study evaluated the impact of empiric MRSA PCR nares screening on de-escalation of vancomycin therapy in critically ill trauma patients. Methods: This is a single center, pre-post observational cohort study conducted at an academic, level I trauma center. Adult patients who were admitted for trauma and received empiric vancomycin therapy for suspected infection in the trauma intensive care unit were included. Patients were grouped by whether they were included 6 months before (pre-cohort) and 6 months after (post-cohort) the implementation of empiric rapid MRSA PCR nares screening in September 2021. The primary outcome was duration of vancomycin therapy. Secondary outcomes included rate of acute kidney injury (AKI), positive MRSA screen or cultures, ICU length of stay (LOS), hospital LOS, and mortality. Results: One-hundred fifty-eight patients were included: 82 in the pre-cohort group and 76 in the post-cohort group. Ninety vancomycin initiation orders were observed in the pre-cohort versus 80 orders in the post-cohort. Baseline demographics were similar between groups. There was a significantly higher rate of MRSA PCR orders in the post-cohort group (75%) compared to (21%) in the pre-cohort (p< 0.001). The pre-cohort group had higher rates of positive MRSA screens (26 vs. 13%, p=0.18) and MRSA positive cultures (17 vs. 9%, p=0.22) compared to post-cohort. There were no reported instances of positive MRSA cultures with a negative PCR. Vancomycin duration was significantly shorter in the post-cohort group (2.55 days vs. 3.5, p=0.02). Hospital and ICU LOS, rates of AKI, and mortality were not different between groups. Conclusions: Implementation of empiric rapid MRSA nares screening led to a shorter overall duration of vancomycin therapy by nearly one day in critically ill trauma patients. Further study is required to evaluate the potential cost savings of empiric MRSA screening in critically ill trauma patients.

Trough-guided Versus AUC/MIC-Guided Vancomycin Monitoring: A Cost Analysis

PurposeRecent vancomycin dosing and monitoring guidelines recommend monitoring vancomycin area under the 24-hour time–concentration curve instead of traditional trough-only monitoring. This study aimed to compare the total costs of vancomycin dosing and monitoring between trough-guided and AUC-guided approaches in a quaternary hospital from Brazil. MethodsIn this retrospective cohort study, patients were divided into 2 groups according to the monitoring method. Patients with previous renal impairment were excluded. Vancomycin AUC was estimated by using 2 steady-state serum concentrations and first-order kinetics equations. The primary outcome was total cost of vancomycin therapy and monitoring from the hospital perspective, which included costs of cumulative doses, laboratory fees, materials used in blood collection, nursing time for collection, and pharmacist time for result interpretation. FindingsA total of 68 patients were included in the AUC/MIC–guided monitoring group, and 76 patients were included in the trough-guided monitoring group. There were no significant differences between groups regarding baseline serum creatinine level, duration of vancomycin therapy, and cumulative vancomycin dose. The median (interquartile range) total vancomycin drug and monitoring cost was $298.32 ($153.81–$429.85) for the AUC/MIC–guided group compared with $285.59 ($198.81–$435.57) for the trough-guided group (P = 0.9658). ImplicationsVancomycin AUC estimation using 2 steady-state serum concentrations and first-order kinetics equations is a feasible alternative for limited-resource institutions that intend to transition from a trough approach to AUC/MIC–guided monitoring.

Clinical utility of negative methicillin-resistant Staphylococcus aureus (MRSA) nasal surveillance swabs in skin and skin structure infections

BackgroundNegative methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs have a high negative predictive value of approximately 99% in respiratory infections. There is, however, a lack of data evaluating its use beyond respiratory infections. MethodsWe conducted a retrospective analysis to determine the clinical utility of MRSA swabs for identifying MRSA-associated skin and skin structure infections (SSSIs) and the potential effects on antimicrobial stewardship efforts. Baseline characteristics, culture data, and antibiotic data were collected to determine the difference in duration of vancomycin therapy. Positive predictive value, negative predictive value, sensitivity, and specificity were secondary outcomes. ResultsA total of 473 patients were included, of which 156 patients had a positive MRSA nasal swab and 317 patients had a negative swab. The median duration of vancomycin was 4 days in the positive group and 3 days in the negative group (P = .01). The positive predictive value and negative predictive value were 22.4% and 97.5%. The sensitivity and specificity were 81.4% and 71.9%. ConclusionPatients with a negative MRSA nasal swab received approximately 1 day less of vancomycin, which represented a decrease in drug administered. The negative predictive value for SSSIs is promising, showing potential for the role of MRSA nasal swabs in de-escalating therapy.

621. Identifying Quality-Improvement Interventions to Improve Inpatient Intravenous Vancomycin Safety at an Academic Medical Center

BackgroundThe reported incidence of intravenous (IV) vancomycin-associated acute kidney injury (AKI) is highly variable. The primary purpose of this study was to determine the baseline rate of IV vancomycin-associated AKI at the University of Utah Hospital (UUH) and Huntsman Cancer Institute (HCI) with the goal of identifying areas of focus for future quality improvement (QI) initiatives.MethodsThis was a retrospective descriptive study of patients ≥ 18 years old, hospitalized at UUH or HCI, who received at least daily scheduled doses of IV vancomycin for ≥ 72 hours between November 1, 2018 and October 31, 2019. AKI was defined using the serum creatinine (SCr) aspect of the AKIN criteria. Variables assessed for association with AKI included demographic characteristics, hospital and unit where vancomycin was initiated, duration of therapy, administration method, and concomitant nephrotoxic medications. Multivariable logistic regression was used to identify variables independently associated with AKI as potential QI interventions.ResultsOne thousand eighty-six patients were included. Baseline patient characteristics are listed in Table 1. Throughout our system, 19.7% of patients experienced an AKI while receiving vancomycin. Univariate comparisons are listed in Table 1. Variables independently associated with AKI on multivariable analysis included total body weight (HR 1.02, 95% CI [1.01-1.03]), concomitant administration of calcineurin inhibitors or vasopressors (HR 1.97, 95% CI [1.18-3.29] and HR 1.68, 85% CI [1.07-2.64] respectively), duration of vancomycin therapy (HR, 1.04, 95% CI [1.02-1.06]), and administration in specific units (see Table 1). Administration of vancomycin by continuous infusion showed a protective effect (HR 0.13, 95% CI [0.02-1.12]) as did baseline SCr and total daily dose of vancomycin (HR 0.76, 95% CI [0.61-0.94] and HR 0.63, 95% CI [0.51-0.78] respectively); the latter two are likely a reflection of the study design. The median hospital length of stay in days was longer in individuals experiencing an AKI (19 vs 10, p < 0.0001).Table 1. Univariate and Multivariate Associations with Vancomycin-Associated Acute Kidney Injury aFor continuous variables, the HR reported is for each unit increaseTable 1. (Continued) Univariate and Multivariate Associations with Vancomycin-Associated Acute Kidney Injury aFor continuous variables, the HR reported is for each unit increaseConclusionSeveral variables associated with vancomycin-associated AKI within our health system were identified. Future QI interventions to improve vancomycin safety will be pursued.Disclosures Russell J. Benefield, PharmD, Paratek Pharmaceuticals (Grant/Research Support)

1097. A Comparison of Area-Under Curve (AUC)-Guided vs Trough-Guided Monitoring of Vancomycin and Its Impact on Nephrotoxicity: A Systematic Review and Meta-analysis

BackgroundTrough levels have been used for Vancomycin (VAN) therapeutic drug monitoring (TDM) historically due to its practicality. A paradigm shift towards the use of area under curve (AUC)-guided dosing TDM has been made due to availability of advanced pharmacokinetics software, variability between trough levels and AUC values and the potential for reducing toxicity. This review aims to evaluate the impact of AUC-guided vs trough-guided vancomycin TDM on nephrotoxicity-related outcomes.MethodsA systematic review was conducted using PubMed®, Embase®, Web of Science®, CINAHL®, Google scholar and Cochrane library® up till 1st January 2021 and was reported according to the PRISMA checklist. Studies which evaluated AUC-guided or trough-guided VAN TDM and vancomycin-associated nephrotoxicity were included. Random effects models were used to compare differences in nephrotoxicity between trough level or AUC based vancomycin TDM due to expected heterogeneity in study designs. PRISMA Flowchart PRISMA flow chart depicting the selection process of studies included in the meta-analysisResultsOf 1191 records retrieved, 57 studies were included. Majority of studies included adult and elderly patients (n=47, 82.5%). The pooled prevalence of nephrotoxicity was lower using the AUC-guided TDM [6.2%, 95% confidence interval (CI): 2.9 – 9.5%] compared to trough-guided TDM [17.0%; 95% CI: 14.7 – 19.2%]. The risk of nephrotoxicity was lower with the AUC-guided approach as compared with the trough-guided approach [OR: 0.53, 95% CI: 0.32–0.89]. AUC thresholds correlated with risk of nephrotoxicity only for the first 96 hours of therapy. A frequency analysis of significant multivariable factors showed that concomitant use of nephrotoxins, VAN trough levels and duration of VAN therapy were most commonly associated with nephrotoxicity.Forest plot comparing the risk of nephrotoxicity of AUC-guided vs trough-guided Forest plot comparing the risk of nephrotoxicity of AUC-guided vs trough-guidedPooled nephrotoxicity rates from AUC-guided monitoring Pooled nephrotoxicity rates from AUC-guided monitoringPooled nephrotoxicity rates from trough-guided monitoring Pooled nephrotoxicity rates from trough-guided monitoringConclusionThe AUC-guided approach appeared to have lower risk of nephrotoxicity which supports the updated American Society of Health-System Pharmacists recommendations. More studies should be performed to evaluate the optimal derivation of AUC and clinical utility of repeated measurements of vancomycin AUC and trough levels.Disclosures All Authors: No reported disclosures

180. Duration of Therapy and Clinical Outcomes in Adult Oncology Patients with Uncomplicated Coagulase Negative Staphylococcal Bacteremia

BackgroundAlthough they are often considered contaminants, coagulase negative staphylococci (CoNS) can be pathogens especially in immunocompromised patients. National and local guidelines recommend treatment durations of 7 to 14 days, depending on specific clinical scenarios. The objective was to characterize the duration of treatment for CoNS bacteremia and clinical outcomes at our cancer center. MethodsWe conducted a retrospective chart review of adult patients ≥18 years old with ≥1 blood culture with growth of CoNS between 1/1/17 and 12/31/19 at our cancer center. Patients with complicated CoNS bacteremia and polymicrobial infections were excluded.ResultsAmong 128 patients identified during the study period, 98 met inclusion criteria (Figure 1). Most patients (N= 92; 94%) had a hematologic malignancy as the underlying oncologic diagnosis, and 68 (69%) were hematopoietic stem cell transplant recipients. The median total antibiotic duration was 13 days, and median duration from the date of 1st negative blood culture was 12 days; 29 (30%) patients were treated for a total duration of >14 days (Figure 2). The catheter was retained in 67 (68%) and exchanged in 4 (4%) of the cases. Three (3%) patients had recurrence of bacteremia within 30 days of treatment completion, and 8 (8%) patients were transferred to the ICU within 7 days of the index blood culture. The 30-day crude mortality rate was 10%. The most commonly used antibiotic for treatment was vancomycin (N= 95; 97%), and 32 (34%) patients on vancomycin had an increase in serum creatinine of ≥ 50% from baseline. Five (5%) patients discontinued vancomycin due to nephrotoxicity, and 4 (4%) patients required hemodialysis.Figure 1. Results Overview Among 128 patients identified during the study period, 98 met inclusion criteria. Of those included, 36 had one set of blood cultures that were positive for CoNS and 62 patients had at least two sets of blood cultures that were positive for CoNS.Figure 2. Duration of Antibiotic Treatment We evaluated duration of treatment based on total antibiotic duration and duration from date of 1st negative blood culture. The number of patients is noted above each bar.ConclusionAlthough the majority of patients were treated for ≤14 days for uncomplicated CoNS bacteremia, nearly 1/3 of patients were treated for > 14 days. Recurrent bacteremia was uncommon despite catheter retention in most patients. Relatively high rates of vancomycin associated nephrotoxicity highlight opportunities for antimicrobial stewardship to limit duration of vancomycin therapy among cancer patients with uncomplicated CoNS bacteremia. Disclosures All Authors: No reported disclosures

Individualized Vancomycin Dosing with Therapeutic Drug Monitoring and Pharmacokinetic Consultation Service: A Large-Scale Retrospective Observational Study.

BackgroundTo date, outcome data with a large sample size and data regarding the clinical outcomes of pharmacokinetic-guided (PK) dosing of vancomycin are limited.AimWe evaluated the pharmacokinetic and clinical outcomes of a PK-guided dosing advisory program, pharmacokinetic consultation service (PKCS), in vancomycin treatment.MethodsWe investigated vancomycin therapeutic drug monitoring (TDM) and PKCS use through a retrospective review of patients who had serum vancomycin trough concentration data from October 2017 to November 2018. Among these patients, we selected non-critically ill adult patients satisfying our selection criteria to evaluate the effect of PKCS. Target trough attainment rate, time to target attainment, vancomycin-induced nephrotoxicity (VIN), vancomycin treatment failure rate, and duration of vancomycin therapy were compared between patients whose dosing was adjusted according to PKCS (PKCS group), and those whose dose was adjusted at the discretion of the attending physician (non-PKCS group).ResultsA total of 280 patients met the selection criteria for the VIN analysis (PKCS, n=134; non-PKCS, n=146). The incidence of VIN was similar between the two groups (PKCS, n=5; non-PKCS, n=5); however, the target attainment rate was higher in the PKCS group (75% vs 60%, P = 0.012). The time to target attainment was similar between the two groups. Further exclusions yielded 112 patients for the clinical outcome evaluation (PKCS, n=51; non-PKCS, n=61). The treatment failure rate was similar, and the duration of vancomycin therapy was longer in the PKCS group (12 vs 8 days, P = 0.008).ConclusionIn non-critically ill patients, an increase in target trough achieved by PKCS did not lead to decreased vancomycin treatment failures, shorter vancomycin treatment, or decreased nephrotoxicity in vancomycin treatment. Considering the excessive amount of effort currently put into vancomycin dosing and monitoring, more selective criteria for individualized pharmacokinetic-guided dosing needs to be applied.

192. The Use of Area Under the Curve to Determine Therapeutic Vancomycin Dosing in Skin and Soft Tissue Infections

BackgroundThe vancomycin AUC/MIC target ratio of 400 to 600 mg*h/L that is recommended (level IA+) in the 2020 IDSA/ASHP vancomycin TDM guidelines is appropriate for patients with complicated MRSA infections; using lower targets for less complicated infections may reduce the risk for nephrotoxicity without compromising efficacy. The current methodology surrounding vancomycin AUC/MIC targets is unrefined, with no source specific targets identified, especially for relatively lower risk MRSA infections such as skin and soft tissue infections (SSTIs).MethodsThis was a retrospective observational study of hospitalized patients at the Veterans Affairs Health Care System in San Diego, CA with a SSTI and prescribed intravenous vancomycin between January 1, 2016 and December 31, 2019. Patients included were adults, 18 years of age and older, treated with IV vancomycin with ≥1 measured concentration for at least one of the ICD-10 CM codes for SSTI. Patients were excluded if they had any of the following SSTIs: (1) osteomyelitis; (2) infection related to chronic ulcers or wounds; (3) head SSTI; (4) peri-rectal SSTI; (5) human or animal bite SSTI; (6) SSTI related to retained foreign body; (7) necrotizing SSTI; (8) surgical site infection. Patients were also excluded if they were undergoing dialysis or had severe immunosuppression.ResultsA total of 722 patients on vancomycin for a SSTI were identified from the database query for screening, and 243 (34%) met inclusion criteria for the study. Classification and Regression Tree (CART) modeling identified a calculated AUC of >253 as having the highest correlation with clinical success. Clinical cure was significantly different between the AUC ≤253 (6/9 [67%]) and AUC >253 (214/234 [91%]) cohorts (p=0.043). There were no differences in hospital length of stay or duration of vancomycin therapy. Nephrotoxicity occurred in seven patients, all of who had AUC >253.ConclusionOverall treatment success in patients with SSTIs was associated with a vancomycin AUC >253, which is lower than the guideline recommended range of 400–600. Identification of vancomycin AUC targets for other low risk sources of infection, such as UTIs, is needed to prevent vancomycin overexposure.Disclosures All Authors: No reported disclosures

Vancomycin Utilization Evaluation in a Major Teaching Hospital in West of Iran

Background: Vancomycin is a potent antibiotic and has central role in the managing of infections with known resistance to other antibiotics or in patients with allergy to beta-lactams. Irrational use of vancomycin is associated with increased morbidity and mortality as well as the antibiotic resistant.&#x0D; Methods: The DUE was done in Imam Reza Hospital, Tabriz, Iran. A total of 100 patients were included during a 6‐month period. We aimed to evaluate vancomycin administration pattern and assess its compliance with Centers for Disease Control and Prevention (CDC) and the American Society of Health-System Pharmacists (ASHP) protocols as the primary outcome and its adverse effects as the secondary outcome.&#x0D; Results: The mean duration of hospitalization and antibiotic therapy were 22.11 ± 1.76 and 19.08 ± 1.51 respectively (mean ± SD). The most causes of vancomycin administration (51%) were for surgery prophylaxis. In 38% of patients, vancomycin administration was not in accordance to standard guidelines. Dose and duration of vancomycin therapy was according to ASHP and CDC guidelines in 74% and 59% of patients. Dose readjustments of antibiotics were necessary in 28 patients which were done in 12 of them. A total of 140 samples were collected from 60 patients. In 30% of patients, vancomycin use was continued without considering the culture results.&#x0D; Discussion: It is important to set practical pharmaceutical and therapeutic infection control committees in hospitals under the clinical pharmacists’ observation. Furthermore, educational programs for health care professionals regarding rational use of antibiotics can be helpful in improving antimicrobial medications utilization and monitoring.&#x0D;

Analysis of influencing factors of trough serum vancomycin concentrations in critically ill neurosurgical patients

To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients. A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol,diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method. In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. (1) The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. (2) The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). (3) There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations. Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.

Vancomycin-Associated Acute Kidney Injury in Critically Ill Adolescent and Young Adult Patients

Background: Risk factors for the development of vancomycin-associated acute kidney injury (AKI) have been evaluated in both pediatric and adult populations; however, no previous studies exist evaluating this in the critically ill adolescent and young adult patients. Objective: Identify the incidence of AKI and examine risk factors for the development of AKI in critically ill adolescents and young adults on vancomycin. Methods: This retrospective review evaluated the incidence of AKI in patients 15 to 25 years of age who received vancomycin, while admitted to an intensive care unit. Acute kidney injury in this population was defined as an increase in serum creatinine by 0.5 mg/dL or 50% from baseline. Patients who developed AKI were evaluated for specific risk factors compared to those who did not develop AKI. Results: A total of 50 patients (20 developed AKI) were included in the study. There was no difference in vancomycin daily dose or duration of vancomycin therapy. Maximum vancomycin trough (31.15 mg/dL vs 12.5 mg/dL, P = .006), percentage of patients with concurrent nephrotoxic medication (95% vs 60%, P = .012) and concurrent vasopressor (55% vs 23%, P = .029) were higher in those who developed AKI. Percentage of patients who underwent a procedure while on vancomycin (35% vs 6.7%, P = .021) was also higher within the AKI group. Conclusions: Vancomycin-associated AKI occurred in 40% of critically ill adolescent and young adult patients. These patients may be more likely to develop vancomycin-associated AKI if they had undergone a procedure, as well as in the presence of high vancomycin trough levels, concurrent nephrotoxic agents, and concurrent vasopressor therapy.

266. Implementation and Evaluation of a Pharmacist-Managed Pediatric Vancomycin Protocol

BackgroundPediatric studies have shown that pharmacist-guided vancomycin dosing leads to reduction in time to initial target vancomycin trough, duration of vancomycin therapy, time to clinical stability, and shorter hospital stay. At Boston Medical Center, 65% of pediatric patients receiving vancomycin did not achieve initial therapeutic troughs between 10 and 20 μg/mL from October 1, 2016 to September 30, 2017. Through implementation of a pharmacist-managed pediatric vancomycin protocol, the project aim was to increase the percentage of patients achieving initial therapeutic troughs from 35% to 60% and percentage of patients achieving therapeutic troughs within 3 days from 67% to 90% by May 1, 2018. Secondary aims included reducing the incidence of supratherapeutic troughs from 10% to 5% and maintaining the incidence of vancomycin-associated nephrotoxicity (VAN) at 0%.MethodsA quality improvement (QI) initiative based on the Institute for Healthcare Improvement Model was utilized, testing change through Plan-Do-Study-Act (PDSA) cycles. In PDSA cycle 1, pharmacists designed and implemented a standardized vancomycin dosing protocol for pediatric patients. In PDSA cycle 2, the addition of area under the curve (AUC)-guided dosing was implemented in select patients. Process and balancing measures included percentage of appropriately drawn vancomycin troughs, provider adherence to the new dosing protocol, and incidence of supratherapeutic troughs.ResultsA total of 32 pediatric patients were assessed. Compared with baseline data, percentage of patients achieving initial therapeutic troughs increased from 35% to 44% and percentage of patients achieving therapeutic troughs within 3 days increased from 67% to 92%. The incidence of supratherapeutic troughs decreased from 10% to 0% and the incidence of vancomycin-associated nephrotoxicity was maintained at 0%.ConclusionStandardized initial vancomycin dosing with increased pharmacy involvement led to more patients achieving initial therapeutic troughs, shorter times to therapeutic troughs, and a reduction in supratherapeutic troughs. Next steps include hospital-wide implementation of a pediatric vancomycin per pharmacy protocol.Disclosures All authors: No reported disclosures.

229. The Role of Antimicrobial Stewardship Program on Appropriate Use, Dose, and Duration of Vancomycin Treatment

BackgroundIn an era of increasing bacterial resistance, antimicrobial stewardship programs (ASP) are essential in guiding judicious antibiotic use and improving patient safety goals. A prior medication use evaluation of vancomycin conducted at Stony Brook University Hospital (SBUH) identified three areas for improvement: (1) vancomycin dosing to achieve target trough concentration, (2) treatment duration, (3) and the use of vancomycin drug assay. As a result, the ASP at SBUH implemented an interdisciplinary team which consists of pharmacists and physicians to optimize these areas.MethodsA prospective quality improvement program was implemented from October 1, 2017 to December 31, 2017. Patients on two medicine units (60 patient beds) were enrolled in the program if they received vancomycin for more than one day and were not on hemodialysis. The ASP monitored for appropriate use of vancomycin as well as providing real-time guidance on dosing and serum concentration monitoring. If vancomycin was not indicated or de-escalation was warranted, the physician was contacted for discontinuation or de-escalation. To evaluate the impact of the program, we selected comparable patients from two other medicine units during the same period as the control group. Duration of vancomycin therapy, the percentage of patients achieving target trough level and 24-hour AUC within 72 hours, and use of vancomycin drug assay were compared.ResultsThere were 84 patients in the intervention group and 142 patients in the control group with similar age, weight, and creatinine clearance. The intervention group achieved a 20% reduction in the days of vancomycin use (median days of therapy 4.55 vs. 5.7 days, P = 0.071), a higher percentage of patient achieving trough level of 10–20 μg/mL (80.65% vs. 51.79%, P = 0.0001) and 24 hour AUC >400 mg hours/L (95.16% vs. 74.6%, P = 0.001), and a lower number of trough levels per course (1.51 vs. 2.54, P = 0.007). The 3-month medication cost savings from the program on these two units was over $6,000.ConclusionAn ASP supervised program led to a reduction in vancomycin days of therapy, early attainment of optimal exposure, and decreased use of laboratory resources. Moreover, the program lowered the overall healthcare cost.Disclosures All authors: No reported disclosures.

Clinical Utility of Methicillin-Resistant Staphylococcus aureus Nasal Screening for Antimicrobial Stewardship: A Review of Current Literature.

Significant clinical and financial consequences are associated with both inadequate and unnecessary exposure to broad-spectrum antibiotics. As such, antimicrobial stewardship programs seek objective, reliable, and cost-effective tests to identify patients at highest or lowest risk for drug-resistant organisms to guide empirical antimicrobial selection. Use of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening to rule out MRSA in lower respiratory tract infections has led to significant reductions in duration of vancomycin therapy. The clinical utility of MRSA nasal screening in other types of infection remains less clear. This review describes the performance of MRSA nasal screening in predicting MRSA infection, highlights practical considerations for use of MRSA nasal screening, and provides guidance for incorporating MRSA nasal screening into clinical practice. With a high negative predictive value when the prevalence of MRSA is low, MRSA nasal screening is a valuable antimicrobial stewardship tool with potential applications beyond lower respiratory tract infections. In appropriately selected patients, negative MRSA nasal screening can prevent initiation or guide discontinuation of anti-MRSA therapy. Antimicrobial stewardship programs should develop institutional guidelines to promote proper use of MRSA nasal screening. Pharmacists are well positioned to assist with education, interpretation, and application of MRSA nasal screening results.

Evaluation of risk factors for vancomycin-induced nephrotoxicity.

Background Vancomycin is a glycopeptide antibiotic of choice for the treatment of serious infections caused by multi-resistant Gram-positive bacteria. However, vancomycin-associated nephrotoxicity (VAN) often limits its use. Previous data suggested a few risk factors of VAN, including higher mean vancomycin trough level, higher daily doses, old age, long duration of vancomycin therapy, and concomitant nephrotoxins. Objective To evaluate the incidence and risk factors of VAN and determine whether higher vancomycin trough concentrations were associated with a greater risk for VAN. Settings A retrospective, observational, single-center study at the 1960-bed university-affiliated tertiary care hospital (Samsung Medical Center), Seoul, Korea. Method A retrospective analysis of adult patients who received vancomycin parenterally in a tertiary care medical center from March 1, 2013 to June 30, 2013 was performed. We excluded patients with a baseline serum creatinine level > 2mg/dL and those who had a history of end-stage renal disease and dialysis at baseline. The clinical characteristics were compared between patients with nephrotoxicity and those without nephrotoxicity to identify the risk factors associated with VAN. Main outcome measure Incidence of VAN and VAN-associated risk factors were analyzed. Results Of the 315 vancomycin-treated patients, nephrotoxicity occurred in 15.2% of the patients. In multivariate analysis, higher vancomycin trough concentrations of > 20mg∕L (OR 9.57, 95% CI 2.49-36.83, p < 0.01) and intensive care unit (ICU) residence (OR 2.86, 95% CI 1.41-5.82, p < 0.01) were independently associated with VAN. Conclusion Our findings suggest that higher vancomycin trough levels and ICU residence might be associated with a greater risk for VAN. More careful monitoring of vancomycin serum trough levels and patient status might facilitate the timely prevention of VAN.

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure.

Dose, duration, and animal sex predict vancomycin-associated acute kidney injury in preclinical studies

BackgroundAlthough the exposure-dependent efficacy thresholds of vancomycin have been probed, less is known about acute kidney injury (AKI) thresholds for this drug. Sensitive urinary biomarkers, such as kidney injury molecule 1 (KIM-1), have shown high sensitivity and specificity for vancomycin-associated AKI. The aims of the study were to determine if there were dose–response curves with urinary KIM-1, and to evaluate the impact of therapy duration and sex on observed relationships. MethodsA systematic review was conducted via PubMed/MEDLINE. Data were compiled from preclinical studies that reported individual subject data for urinary KIM-1 concentrations, vancomycin dose (mg/kg), duration of treatment, and sex. Sigmoidal Hill-type models were fit to the individual dose-response data. ResultsA total of 15 studies were identified, 6 of which reported vancomycin dose and KIM-1 data. Of these, three included individual animal-level data suitable for analysis. For all pooled rats, increasing total daily vancomycin doses displayed a dose-response curve with urinary KIM-1 concentrations (50% maximal toxic response=130.4 mg/kg/day). Dose-response curves were shifted left for females vs. males (P = 0.05) and for long (i.e. ≥7 days) vs. short (i.e. <4 days) duration of vancomycin therapy (P=0.02). ConclusionsThe collective findings demonstrate a clear dose–response relationship between vancomycin dose and AKI. As these analyses focused exclusively on dose-response relationships, additional preclinical data are needed to more clearly define vancomycin exposures that predict the onset of AKI.

Efficacy and Safety of a Vancomycin (VAN) Dosing Protocol Developed for Morbidly Obese (MO) Patients

BackgroundAn optional VAN loading dose (LD) of 25–30 mg/kg (total body weight), followed by maintenance dose (MD) of 15–20 mg/kg intravenously (IV) Q8–12H is recommended for patients with normal renal function. Studies suggest MO patients may require lower mg/kg doses to achieve therapeutic trough concentrations (TTCs). Our institutional VAN dosing protocol for MO patients (BMI ≥ 40 kg/m2) was revised in 2015 to recommend: LD 25–30 mg/kg (max 3000 mg), MD 12.5–15 mg/kg (max 2000 mg) IV Q8–12H. We evaluated initial TTC attainment, clinical and safety endpoints post protocol revision.MethodsMO adult patients who received IV VAN between June 1, 2012–May 31, 2013 (pre-protocol revision) and August 1, 2015–July 31, 2016 (post-protocol revision) were included. Perioperative VAN, one-time doses, pregnancy, cystic fibrosis, hemodialysis and patients receiving VAN prior to admission were excluded.ResultsA total of 615 patients were screened, with 200 included for analysis (100 per group). Baseline demographics and VAN dosing are shown in Table 1. Initial TCs were drawn for 86 patients in the pre-revision group, and for 69 patients in the post-revision group. Initial VAN TCs are displayed in Table 2. Duration of VAN therapy was significantly shorter post-revision (5 days vs. 2 days, p ≤ 0.01). Mortality (14% vs. 10%, P = 0.38) and hospital length of stay (8.5 days vs. 7 days, p=0.09) were comparable between groups. There was no difference in the incidence of VAN-associated nephrotoxicity (16% vs. 10%, P = 0.20).Table 1Baseline Demographics Pre-Revision (n = 100) Post-Revision (n = 100) P Value Age, years53.7 ± 13.748.8 ± 15.60.06Gender, male21%17%0.47BMI, kg/m244.5 (41.0–49.0)45.5 (41.5–50.8)0.33Frequency of LD30%68%< 0.01Initial MD, mg/kg15.0 (12.8–17.0)14.0 (12.9–15.0)< 0.01Table 2.Initial VAN TCs Pre-Revision (n = 86) Post-Revision (n = 69) P Value Therapeutic35%51%0.05TC, μg/mL17.1 (12.9 – 22.6)17.4 (13.4 – 24.0)0.57Subtherapeutic34%19%0.04Supratherapeutic31%30%0.90ConclusionThe revised VAN dosing protocol for MO patients improved initial TTC attainment and decreased incidence of subtherapeutic TCs compared with current standard of care recommendations with no difference in clinical or safety outcomes.Disclosures All authors: No reported disclosures.