Discontinuation Of Vancomycin Research Articles

Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc): study protocol for a randomized controlled trial

BackgroundVancomycin, an antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial.MethodsSTOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. The objective of this study is to test whether the use of MRSA PCR testing can safely reduce inappropriate vancomycin use in an intensive care setting. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the expected number of hours alive and free of the use of vancomycin within the first 7 days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin.DiscussionSTOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting.Trial registrationClinicalTrials.gov NCT06272994. Registered on February 22, 2024.

A rare occurrence of Vancomycin-induced gastrointestinal hemorrhage without thrombocytopenia: a case report and literature review

BackgroundVancomycin-induced bleeding has been reported, attributed to the mechanism of immune thrombocytopenia. A rare case of vancomycin-induced gastrointestinal hemorrhage in a young patient with no underlying disease, receiving intravenous vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) infection, is presented. This occurrence occurred without thrombocytopenia. Relevant cases reported in the literature were also reviewed.Case presentationA 34-year-old male patient presented with maxillofacial multiple spaces infection accompanying left temporal abscess, bilateral lung abscesses. Culture results from both blood and secretion indicated that the infection was caused by MRSA. The patient received standard-dose vancomycin (1 g q12h intravenously guttae) for treatment. On the 5th day of therapy, he presented with bright red blood in his stool; however, vancomycin treatment was continued. By the 9th day, a decrease in hemoglobin level to 76 g/L and a platelet (PLT) count of 424 × 109/L raised concerns about gastrointestinal hemorrhage. The hemoglobin level decreased to 62 g/L on day 12. Due to the high tissue concentration of linezolid, administration of linezolid at a dose of 600 mg q12h intravenously guttae commenced on the 13th day as an alternative to vancomycin(D13-D17). Subsequently, on the 17th day, there was an improvement in hemoglobin level to 78 g/L. However, despite treatment with linezolid, the patient’s fever showed no significant improvement, prompting a switch back to vancomycin at a dosage of 1 g q12h intravenously guttae(D18-D22). On the 21st day, there was a recurrence of gastrointestinal hemorrhage, accompanied by a hemoglobin level of 42 g/L and a PLT count of 224 × 109/L. Gastroscopy revealed the presence of a gastroduodenal ulcer. The patient had no prior history of hemorrhoids, gastrointestinal ulcers, liver cirrhosis, or purpura. Prior to admission, he had not been administered non-steroidal anti-inflammatory drugs (NSAIDs) or steroids. During hospitalization, the only medications given were vancomycin, ambroxol and lidocaine. Additional tests ruled out immunological disorders as the cause of gastrointestinal ulcers, and a positive vancomycin rechallenge test indicated an association between vancomycin and bleeding. After discontinuation of vancomycin, no further bleeding occurred. This case highlights a rare occurrence of vancomycin-induced bleeding without thrombocytopenia, classified as “Certain” according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale for standardized case causality assessment.ConclusionThis case represents the first documented instance of vancomycin-induced bleeding without thrombocytopenia, as confirmed by a positive rechallenge test. This discovery will aid in the early detection of this rare adverse reaction in future cases.

Impact of Stewardship Pharmacist Driven MRSA Nasal Surveillance and De-escalation of Anti-MRSA Therapy

Background: Intravenous vancomycin is commonly used as initial empiric coverage for pneumonia but is often unnecessary. MRSA nasal surveillance cultures (MRSA nasal swab) have been highlighted in recent literature and the 2019 IDSA Pneumonia Treatment Guidelines as a tool to avoid unnecessary MRSA coverage in pneumonia. A negative MRSA nasal swab can be utilized by clinicians to de-escalate anti-MRSA therapies for pneumonia. The purpose of this study is to determine if implementing stewardship pharmacist driven MRSA nasal surveillance increases use of the test and reduces the inappropriate use of vancomycin for MRSA coverage in patients with pneumonia. Method: This study was a retrospective chart review and was approved by the Trinity Health of New England Institutional Review Board. For this initiative, a stewardship pharmacist evaluated all patients receiving vancomycin for anti-MRSA therapy at Saint Francis Hospital and Medical Center in Hartford, CT. If the patient’s indication was pneumonia and a MRSA nasal swab had not been ordered, the pharmacist contacted the patient’s provider and requested an order for it. Upon receipt of a negative MRSA nasal swab result, the pharmacist recommended discontinuation of vancomycin to the provider if appropriate. Outcomes from the first four weeks of the pharmacist-driven initiative (April 10, 2023 to May 5, 2023) were compared to the four weeks prior to the initiative (March 13, 2023 to April 7, 2023) as a control group. The primary outcome of this study was percentage of patients who received a MRSA nasal swab. Secondary outcomes included percentage of patients who had vancomycin appropriately de-escalated based on MRSA nasal swab results and mean length of vancomycin therapy. Result: 116 patients met inclusion criteria: 61 in the control group and 55 in the intervention group. Percentage of swabs ordered increased from 36.1% (22/61) without pharmacist intervention to 80.0% (44/55) with pharmacist intervention (p < 0 .0001). There were also increased rates of vancomycin de-escalation in patients with pharmacist intervention, with 58.2% (32/55) of patients in the intervention group having vancomycin discontinued following a negative MRSA swab compared to 19.7% (12/61) in the control group (p < 0 .0001). Conclusion: The results suggest implementing a pharmacist driven MRSA nasal surveillance program into practice could increase the number of MRSA nasal swabs ordered and in turn promote more timely de-escalation of vancomycin in patients with pneumonia. The results from this study can be used to support the wide-spread use of pharmacist driven MRSA nasal surveillance protocols at other institutions.

Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc): study protocol for a randomized controlled trial.

Vancomycin, an antibiotic with activity against Methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial. STOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the number of hours alive and free of the use of vancomycin within the first seven days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin. STOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting. This trial was registered on ClinicalTrials.gov on February 22, 2024. (ClinicalTrials.gov identifier: NCT06272994).

Vancomycin nephrotoxicity: A comprehensive clinico-pathological study.

Vancomycin, a commonly prescribed antibiotic particularly in the setting of multi-drug resistant infections, is limited by its nephrotoxicity. Despite its common occurrence, much remains unknown on the clinicopathologic profile as well as the pathogenesis of vancomycin nephrotoxicity. Clinical studies included patients often with severe comorbidities and concomitant polypharmacy confounding the causal pathogenesis. Animal models cannot recapitulate this complex clinical situation. Kidney biopsy was not commonly performed. To address this limitation, we studied 36 patients who had renal biopsies for acute kidney injury (AKI) for suspicion of vancomycin nephrotoxicity. Detailed renal biopsy evaluation, meticulous evaluation of clinical profiles, and up-to-date follow-up allowed for a diagnostic categorization of vancomycin nephrotoxicity (VNT) in 25 patients and absence of vancomycin nephrotoxicity (NO-VNT) in 11 patients. For careful comparison of these two groups, we proceeded to compile a clinicopathologic and morphologic profiles characteristic for each group. Patients with VNT had a characteristic clinical profile including a common clinical background, a high serum trough level of vancomycin, a rapidly developed and severe acute kidney injury, and a recovery of renal function often shortly after discontinuation of vancomycin. This clinical course was correlated with characteristic renal biopsy findings including acute tubulointerstitial nephritis of allergic type, frequent granulomatous inflammation, concomitant and pronounced acute tubular necrosis of nephrotoxic type, and vancomycin casts, in the absence of significant tubular atrophy and interstitial fibrosis. This clinico-pathologic profile was different from that of patients with NO-VNT, highlighting its role in the diagnosis, management and pathogenetic exploration of vancomycin nephrotoxicity. Vancomycin nephrotoxicity has a distinctive morphologic and clinical profile, which should facilitate diagnosis, guide treatment and prognostication, and confer pathogenetic insights.

Antibiotic stewardship bundle for uncomplicated gram-negative bacteremia at an academic health system: a quasi-experimental study.

To evaluate whether an antimicrobial stewardship bundle (ASB) can safely empower frontline providers in the treatment of gram-negative bloodstream infections (GN-BSI). From March 2021 to February 2022, we implemented an ASB intervention for GN-BSI in the electronic medical record (EMR) to guide clinicians at the point of care to optimize their own antibiotic decision-making. We conducted a before-and-after quasi-experimental pre-bundle (preBG) and post-bundle (postBG) study evaluating a composite of in-hospital mortality, infection-related readmission, GN-BSI recurrence, and bundle-related outcomes. New York University Langone Health (NYULH), Tisch/Kimmel (T/K) and Brooklyn (BK) campuses, in New York City, New York. Out of 1097 patients screened, the study included 225 adults aged ≥18 years (101 preBG vs 124 postBG) admitted with at least one positive blood culture with a monomicrobial gram-negative organism. There was no difference in the primary composite outcome (12.9% preBG vs. 7.3% postBG; P = 0.159) nor its individual components of in-hospital mortality, 30-day infection-related readmission, and GN-BSI recurrence. Vancomycin (VAN) discontinuation (DC) was done more frequently by the primary team in postBG (37.9% vs 66.7%; P < 0.001). In postBG, de-escalation done by the primary team increased by 8.8%, P = 0.310 and there was an 11.1% increase in the use of aminopenicillin-based antibiotics, P = 0.043. GN-BSI bundle worked as a nudge-based strategy to guide providers in VAN DC and increased de-escalation to aminopenicillin-based antibiotics without negatively impacting patient outcomes.

Impact of a pharmacy-driven MRSA nares screening protocol on vancomycin discontinuation in a tele-antimicrobial stewardship model.

A pharmacist-driven protocol for methicillin-resistant Staphylococcus aureus nares screening and empiric vancomycin discontinuation was instituted in a community healthcare system utilizing a tele-antimicrobial stewardship program to reduce inappropriate use of vancomycin. The protocol and associated intervention resulted in a significant decrease in both vancomycin utilization and the rate of acute kidney injury.

2240. Breaking Dogmas: A Single Center Evaluation of Empiric Vancomycin Use Among Intensive Care Unit Patients with Suspected Pneumonia, Bacteremia or Sepsis

Abstract Background Augmented concern for methicillin-resistant Staphylococcus aureus (SA) infections in intensive care units (ICU) has led to increased empiric vancomycin use (EVU) in patients with suspected pneumonia, bacteremia, and/or sepsis. At Tufts Medical Center, vancomycin is prescribed at clinician discretion without restrictions. We aimed to evaluate the impact of cultures on EVU and identify predictors associated with prolonged EVU among ICU patients with cultures negative (CN) for SA. Methods A retrospective study from April 2022 to January 2023 of ICU adult patients with EVU for suspected pneumonia, bacteremia, or sepsis was conducted. ICU service, length of stay (LOS), duration of EVU, blood &amp; respiratory cultures, mechanical ventilation (MV), central line presence, and vasopressor use were collected. Prolonged EVU was defined as vancomycin use for more than 2 days despite CN for SA. The primary outcome was the rate of prolonged EVU discontinuation. Linear regression included demographics, ICU service, LOS, indication, Charlson Co-morbidity Index, lactate, MV, and 0.5 mg/dL serum creatinine change. Logistic regression included the same variables plus age, positive respiratory cultures and MV interaction. Results A total of 165 ICU patients had EVU. Of these, 132 (80%) had cultures collected before EVU vs. 33 (20%) that did not. Blood cultures were collected in 117 (88.6%); 66 (49.6%) had respiratory cultures; 51 (38.6%) had both collected. Median vancomycin duration was 2 days (1-3). Prolonged EVU was observed in 47 (46.1%) patients, while 55 (53.9%) had EVU discontinued within 2 days with CN for SA. On average Cardiac Surgery (CS) spent 2 days longer on vancomycin compared to Surgical (p=0.037) and Pulmonary (p=0.01) patients. MV among ICU patients was less likely to be associated with vancomycin discontinuation within 2 days with CN for SA (aOR [adjusted odd ratio] 0.12, 95% CI 0.03, 0.50; p=0.003). Conclusion EVU discontinuation was more likely within 2 days in ICU patients with CN for SA, but less likely for MV or CS patients. In a substantial proportion of patients, cultures were not collected. Our findings highlight the importance of diagnostic testing in ICU settings to help reduce EVU. Disclosures Maureen Campion, PharmD, Shinoigi: Speaker

329. Vancomycin area under the concentration-time curve monitoring from Bayesian modeling in outpatient parenteral antimicrobial therapy

Abstract Background Current vancomycin monitoring guidelines recommend area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) monitoring for patients with serious MRSA infections. Most AUC monitoring studies have included hospitalized patients only; however, many patients complete vancomycin therapy in the outpatient setting. While traditional two-level AUC calculations are logistically challenging for outpatients, Bayesian modeling software can allow for single level AUC estimations. There are sparse data on the feasibility, safety, and efficacy of vancomycin AUC monitoring in OPAT. Methods We conducted a single-center, quasi-experimental, interrupted time series study of adult patients enrolled in the OPAT program at our institution for vancomycin management. Our institution implemented a pharmacist-driven vancomycin monitoring program using AUC targets from September 8th, 2019 to February 25th, 2020, and again from September 25th, 2022 to March 16th, 2023. Patients enrolled in the monitoring program underwent vancomycin monitoring using an AUC goal of 400-600 mg*hr/L, estimated using Bayesian modeling. A cohort comprising all patients enrolled in the OPAT program from July 4th, 2021 through August 27th, 2022 for trough only vancomycin monitoring was used for comparison. Patients were excluded from analysis if they were undergoing renal replacement therapy at baseline, enrolled in OPAT for ≤ 72 hours, or did not have vancomycin levels drawn for ≥ 14 days. The primary outcome was nephrotoxicity defined as a serum creatinine increase by ≥ 0.5 mg/dL or ≥ 50% during outpatient vancomycin therapy. Results There were 63 patients in the AUC arm, and 60 patients in the trough-only arm. The incidence of nephrotoxicity was lower in the AUC cohort (6.3% vs 23.3%, p=0.01). There was no difference in other vancomycin-related adverse event rates (1.6% vs 10.0%, p=0.06). Vancomycin discontinuation due to adverse event was lower in the AUC arm (6.3% vs 20.0%, p=0.03). Conclusion Patients undergoing AUC monitoring were significantly less likely to develop nephrotoxicity during outpatient vancomycin treatment. Bayesian modeling represents a viable and safe option for vancomycin AUC monitoring in OPAT. Disclosures David W. Kubiak, PharmD, BCPS, BCIDP, FIDSA, Astellas Pharma, Inc.: Advisor/Consultant|AVIR Pharma Inc: Advisor/Consultant|Cidara Therapeutics: Advisor/Consultant|Shionogi Inc: Grant/Research Support

Vancomycin-induced bullous dermatosis: a rare case report.

The authors present here a case of a 61-year-old woman with a history of HTN. The patient had a discectomy 15 years ago, and also underwent a lumbar fusion surgery that resulted in complications with her discitis. Due to the complications from the surgery, intravenous treatment with vancomycin and meropenem was initiated. After a few days of treatment, the patient developed clear, tense, fluid-filled bullae over the upper extremities. Immunofluorescence microscopy is not available in our hospital. Therefore a diagnosis of vancomycin-induced LABD was proposed based on the clinical manifestation of the lesions and the coincidence with vancomycin administration. After 2 days of discontinuing the administration of vancomycin and applying local diprosone, the lesions started to regress and a full recovery was achieved on day 10. Even though drug-induced LABD is uncommon, its incidence has been steadily increasing in the last few years. LABD is a simple condition with a good prognosis and full recovery after the discontinuation of vancomycin.

Necessity of vancomycin trough concentrations to manage uncomplicated acute bacterial skin and skin structure infections: a laboratory stewardship analysis.

Recent recommendations by the American Society of Health System Pharmacists and Infectious Disease Society of America have provided guidance regarding vancomycin dosing and monitoring in serious infections (including methicillin-resistant Staphylococcus aureus); however, trough monitoring for uncomplicated acute bacterial skin and skin structure infections (ABSSSI) were not addressed. Vancomycin use appears to lead to a low incidence of acute kidney injury with short durations and a low trough goal (10-15 mg/L). Nevertheless, clinical studies have found no difference in clinical outcomes for ABSSSI regardless of vancomycin level. Therefore, it can be posed whether trough monitoring is necessary in this patient population. This is a retrospective cohort study comparing vancomycin therapy duration for ABSSSI in adult, general medicine patients who received scheduled vancomycin with an initial creatinine clearance rate of ≥50 mL/minute and had at least one vancomycin trough. The objective of this study was to determine if vancomycin treatment duration differs for patients with ABSSSI with a sub-therapeutic vancomycin trough (ST; <10 mg/L) compared with therapeutic trough (TT; ≥10 mg/L). There were 39 (67.2%) patients with ST compared with 19 (32.8%) with TT. A similar median vancomycin treatment duration for ST (48.25 hours) and TT (59.5 hours; p=0.65) was found. There was no statistical difference for hospital duration, time from last trough to vancomycin discontinuation, or incidence of acute kidney injury (p>0.05 for all). Patients with ST and TT had similar vancomycin durations and clinical outcomes. It may be prudent for institutions to address vancomycin trough laboratory stewardship and associated costs.

Characterization of Febrile Neutropenia Management in Children With Malignancies: A Single-Center Evaluation.

Current recommendations for febrile neutropenia (FN) include initiation of broad-spectrum antibiotics without clear indications of when or how to de-escalate or target therapy, especially in those without microbiologically defined bloodstream infections (MD-BSIs). The purpose of this study is to characterize a pediatric FN population, FN management, and identify the proportion of patients with MD-BSI. This study was a single-center, retrospective chart review of patients admitted to the University of North Carolina Children's Hospital between January 1, 2016, and December 31, 2019, with a diagnosis of FN. There were 81 unique encounters included in this study. MD-BSI was the etiology of fever in 8 FN episodes (9.9%). The most common empiric antibiotic regimen was cefepime (62%) followed by cefepime and vancomycin (25%). The most common de-escalation type was the discontinuation of vancomycin (83.3%), and the most common type of escalation was the addition of vancomycin (50%). The median antibiotic total duration in patients without MDI-BSI was 3 days (IQR, 5-9). In this single-center, retrospective review, most FN episodes were not due to an MD-BSI. There were inconsistencies in practice of when discontinuation of antibiotic therapy occurred in patients without MD-BSI. De-escalation or cessation of antibiotic therapy before neutropenia resolution did not result in any documented complication. These data suggest a role for implementing an institutional guideline to improve consistency in antimicrobial use in pediatric patients with febrile neutropenia.

Vancomycin-induced elevation of liver enzyme levels in a 3-year-old boy with bacterial meningitis: A pediatric case report

BackgroundVancomycin as a glycopeptide antibiotic agent plays a vital role in the treatment of gram-positive bacterial infections, especially methicillin-resistant Staphylococcus aureus. Vancomycin-induced liver disease is rarely reported previously; isolated cases have been reported only in adults and none in children except in a 3-month-old girl published in a Chinese journal. Case SummaryA 3-year-old boy received vancomycin for the treatment of bacterial meningitis for more than 3 weeks. The baseline liver enzyme levels of alanine aminotransferase (ALT) (12 U/L), aspartate aminotransferase (AST) (18 U/L), and gamma-glutamyl transferase (GGT) (26 U/L) were obtained after administering vancomycin for 2 days. Liver enzyme levels of ALT (191 U/L), AST (175 U/L), and GGT (92 U/L) were obviously elevated after administering vancomycin for 22 days; this elevation was reversed after vancomycin discontinuation. This case suggested that regular examination of liver function is necessary for all individuals who initiated vancomycin. Practice ImplicationsThis is a rarely known case of vancomycin-induced elevation of ALT and AST and the first reported case of vancomycin causing GGT elevation in children, which suggested that regular examination of liver function is required during the use of vancomycin in children and could help avoid progressive liver injury. This case adds to the limited number of reports on vancomycin-induced liver disease.

An Unusual Case of Low Vancomycin Exposure Despite Extremely High Vancomycin Doses Accompanied by Renal Toxicity: A Grand Round.

This grand round describes the case of a patient who received 10 grams (143.5 mg/kg) of vancomycin every 24 hours via continuous infusion, in whom the highest observed level was only 15.4 mg/L. Despite subtherapeutic levels, renal impairment was encountered, which resolved after the discontinuation of vancomycin. Glomerular hyperfiltration was found through nuclear glomerular filtration rate measurement, which likely explains the need for high doses (>6 grams per 24 hours continuous infusion) without reaching therapeutic serum levels.

610. Low Rates of Acute Kidney Injury (AKI) in Outpatient Vancomycin Managed by Pharmacists using Precision Dosing Software

Abstract Background AKI is a complication of intravenous vancomycin (VAN) occurring in up to 43% of patients (pts) during hospitalization. Data on AKI in pts receiving VAN through outpatient parenteral antimicrobial therapy (OPAT) are limited. There is suggestion that VAN managed through precision dosing pharmacokinetic (PK) software may limit this occurrence. We evaluated the AKI rate of pts receiving VAN as OPAT through Physician Office Infusion Centers (POICs) over a 12-month period. Methods A review was conducted of OPAT VAN pts treated in 2021 with therapeutic drug monitoring (TDM) performed (InsightRX) and ≥2 VAN serum levels. These pts were then evaluated for AKI, defined as increase in serum creatinine (SCr) ≥1.5 times baseline. Pts on dialysis were excluded. Data included comorbidities, diagnosis, VAN regimen, concomitant medications, SCr, and VAN serum levels. PK parameters were collected with trough values and estimated 24-hr area under the curve (AUC24). Outcome of therapy was assessed following identification of AKI. Results A total of 330 pts from 51 POICs had TDM performed. Of these, 27 (8.2%) developed AKI. Median age was 61 years, 67% were male, and baseline SCr was 0.8 mg/dL (IQR, 0.7-1.0). Most pts (89%) were on concomitant nephrotoxic medications. Median duration of OPAT was 34 days (IQR, 18-41) with onset of AKI after 16 days (IQR, 10-21). At time of AKI, the median SCr increase was 1.7 times baseline (IQR, 1.5-2.0) with a corresponding VAN trough of 21 mg/mL (IQR, 15-28) and AUC24 of 572 mg*h/L (IQR, 495-660). As a result, VAN was discontinued in 14 (52%), dose or frequency modified in 10 (37%) with completion of VAN, and no modifications performed in 3 (11%). One pt who discontinued VAN required hospitalization due to AKI with resolution. Conclusion VAN managed by pharmacists in an OPAT setting using precision dosing software resulted in a low rate of AKI. Median rise in SCr was &amp;lt; 2 times baseline for those with AKI. Rapid identification of early AKI by the pharmacist resulted in changes to the regimen or VAN discontinuation, preventing serious patient sequelae. This supports the need for pharmacist-led monitoring in an outpatient setting with long VAN therapy durations. Disclosures Lucinda J. Van Anglen, PharmD, Merck &amp; Co.: Grant/Research Support|Paratek: Grant/Research Support.

959. It Takes a Village: Reducing Empiric Vancomycin Use by Leveraging Primary Team Pharmacist Oversight of a 72-hour Approval Process

Abstract Background Vancomycin is often initiated empirically in hospitalized patients for broad spectrum gram-positive coverage, however in many cases it is initiated unnecessarily and/or continued empirically for longer durations than necessary. Strategies to facilitate timely discontinuation of vancomycin when unnecessary may reduce antibiotic toxicity (e.g. nephrotoxicity) and the development of bacterial resistance. In large hospital systems, it may not be feasible for stewardship programs to implement prior authorization requirements or prospective audit/feedback for all vancomycin orders. Novel strategies to enlist other clinicians to serve as stewards of antibiotic use are needed. Methods On February 1, 2020, we implemented a protocol requiring providers to obtain approval from the primary team pharmacist to continue empiric vancomycin regimens &amp;gt;72 hours. Primary team pharmacists were provided a list of appropriate indications for vancomycin continuation. After 72 hours, the pharmacist placed a note describing the approved indication or if ASP or ID consult was obtained. We evaluated the standardized antibiotic administration ratio (SAAR) for antibacterial agents for resistant gram-positive infections for FY2019 (pre-protocol) and FY2020 (post-protocol) to assess the impact of this intervention. Vancomycin utilization was also evaluated in days of therapy (DOT)/1000 patient days during both time periods. Results The SAAR for antibacterial agents for resistant gram-positive infections for FY2019 was 1.17 and FY2020 was 1.04 (95% CI (0.87, 0.91), p-value &amp;lt; 0.001). A significant reduction in SAAR was observed in patients admitted to the ICU and floor (Figure 1). Overall vancomycin utilization according to days of therapy/1000 patient days was reduced from 111.13 (FY2019) to 104.08 (FY2020). Conclusion Leveraging the oversight of primary team pharmacists proved to be an effective strategy to reduce empiric vancomycin durations of therapy. Following the implementation of a 72-hour approval protocol with primary team pharmacist oversight, we observed a significant reduction in the SAAR for antibacterials for resistant gram-positive infections with a corresponding reduction in vancomycin utilization. Disclosures All Authors: No reported disclosures.

598. Area under the curve-guided vancomycin monitoring and risk of nephrotoxicity in non-Staphylococcus aureus infections: A case-control study

Abstract Background Area under the curve (AUC)-guided monitoring of vancomycin for the treatment of Staphylococcus aureus (SA) infections demonstrates reduced rates of nephrotoxicity in clinical studies. Many institutions utilize AUC-guided dosing for all patients receiving vancomycin, despite extrapolated AUC goals for non-SA infections. We sought to define risk factors for vancomycin-induced kidney injury (VIKI) in non-SA infections. Methods This was a retrospective, single-center, case-control study evaluating risk factors associated with VIKI in hospitalized patients receiving AUC-guided dosing for non-SA infections from 2/2019-10/2021. Cases were defined as patients with non-SA infections who received &amp;gt;72 hours of vancomycin and had &amp;gt;1 observed vancomycin concentration with a corresponding AUC calculated who developed VIKI within 24 hours of vancomycin discontinuation. Controls had to meet all case criteria but did not have VIKI. Univariate and multivariable analyses were used to identify risk factors associated with VIKI. Multivariable analyses were conducted using the Optimal Data Analysis package for R. Results Twenty-three cases and 48 controls were included. Leading indications were bloodstream (52.1%) and severe skin/skin structure (46.5%) infections. Isolated pathogens from culture included coagulase-negative Staphylococcus (49.3%) and Streptococcus spp. (43.7%). The majority of vancomycin AUCs (52%) were collected within 24-48 hours of initiation. The median first and second AUCs were higher in cases vs. controls [429 vs. 385 mg*hr/L, p=0.013; and 573 vs. 429 mg*hr/L, p=0.021], respectively. Most patients (75%) experienced AKI within 72 hours of vancomycin initiation, with a median time to AKI of 5 days (IQR 2.5-7). Risk factors associated with AKI included any AUC exceeding 515 mg*hr/L, infection caused by pathogens other than Streptococcus spp., and non-bacteremia indications. Patients with AUCs exceeding 515 mg*hr/L had 3.7-fold greater odds of VIKI (p=0.017). Conclusion We found that higher AUCs increased the risk of VIKI in non-SA infections and that the risk of VIKI varied by vancomycin indication. Our findings agree with previous studies in SA indicating that vancomycin AUC should not generally exceed 515 mg*hr/L. Disclosures Nathaniel J. Rhodes, PharmD MS, Paratek: Grant/Research Support|Third Pole Therapeutics: Advisor/Consultant.

1790. Dethroning Vancomycin: A Multifaceted Stewardship Approach to Reduce Vancomycin in an Academic Medical Center

Abstract Background Vancomycin is a broadly used antimicrobial, and from 2014-2022 represented the most used antibiotic at our academic medical center. Since 2015, the stewardship program has introduced several measures to optimize vancomycin use including pharmacy consultation, addition of MRSA nares PCR testing, embedding MRSA nares PCR order into vancomycin order panel, and introducing an electronic medical record (EMR) best practice alert to assist providers in identifying patients eligible for vancomycin discontinuation. The impact of each of these interventions are described. Methods This is a retrospective, single academic center, comparison of vancomycin utilization over time, following the introduction of various stewardship measures. Each intervention remained in place during subsequent periods. Wilcoxon rank sum was used for analysis. Period 1 (P1): 4/2015-12/2016 vancomycin pharmacy consultPeriod 2 (P2): 1/2017-6/2019 pharmacists authorized to order Nasal MRSA PCRPeriod 3 (P3): 7/2019-2/2020 embed nasal MRSA PCR into consult panelPeriod 4 (P4): 2/2020-3/2022 addition of automated EMR time-out Results Each period of vancomycin optimization was associated with a statistically significant decrease in vancomycin length of therapy (LOT) in days, when compared to the period before it (P1 vs P2, p&amp;lt; 0.0001; P2 vs P3, p&amp;lt; 0.0001; P3 vs P4, p&amp;lt; 0.0001). Overall institution vancomycin consumption, expressed as monthly days of therapy (DOT)/1000 patient days (PD) also decreased over time, starting with period 3 (P1 vs P2, p=0.4812; P2 vs P3, p=0.0003; P3 vs P4, p=0.0019) (Table 1). Table 1Vancomycin utilization trends over 4 periods of stewardship intervention. Conclusion Decreasing vancomycin at an academic medical center is challenging and takes a multifaceted approach with continued efforts over time to maintain a steady downward trend for utilization. These combined efforts have led to vancomycin no longer being the most commonly prescribed antibiotic at our institution. Disclosures All Authors: No reported disclosures.

1791. Leveraging EMR Alerts for Vancomycin Time Outs

Abstract Background Vancomycin represented the most used antibiotic at our academic medical center from 2014-2022. To enhance compliance with the “antibiotic time out” part of the CDC Core Elements for Stewardship, we designed an electronic medical record (EMR) best practice alert (BPA) to assist providers in identifying patients eligible for vancomycin discontinuation. Methods This is a single center, retrospective pre (06/01/14-2/24/20)/post (02/25/20-03/31/22) comparison of vancomycin utilization after the introduction of a locally validated automated vancomycin time-out. The BPA alerted on patients who had received vancomycin for 72h, had no microbiological evidence of methicillin resistant S. aureus, and had no infectious diseases consult. While other vancomycin reduction strategies had previously been implemented as part of the stewardship program, no other intervention debuted during the same time period. An interrupted time series analysis was performed to assess immediate and ongoing trend changes of institutional vancomycin use. Wilcoxon rank sum and chi2 analyses were also performed. Results There were 36,817 inpatient vancomycin orders placed. The BPA triggered during 1,881 (15.7%) orders in the post-BPA period, which was 49.6% of the 3,794 orders still active at 72h. After BPA introduction, there was an immediate decrease in vancomycin days of therapy (DOT)/1000 patient days (PD) ±SE (-8.5 ±3.6; P = 0.021) followed by a significant decrease in the monthly trend relative to the pre-intervention trend (-0.7 DOT/1000 PD ±0.2; P&amp;lt; 0.001). Median vancomycin DOT/1000 PD decreased from 145.9 (IQR 140.2-153.0) to 117.3 (IQR 107.7-122.6) in pre and post periods respectively (P&amp;lt; 0.001). Length of therapy (LOT) decreased, orders were more commonly discontinued by day 5, and orders were more likely to be discontinued prior to discharge. Separate analysis including only orders with &amp;gt;72h showed similar results (Table 1). Table 1Vancomycin length of therapy (LOT) pre and post-BPA Time Out.Figure 1Vancomycin days of therapy per 1000 patient days (DOT/1000PD) trends pre and post-BPA Time Out. Conclusion Introduction of an EMR automated vancomycin time out was an effective tool to decrease vancomycin utilization at an academic medical center. Disclosures All Authors: No reported disclosures.

The systemic immune response due to cholesterol crystal embolization syndrome: a case report

BackgroundCholesterol crystal embolization syndrome (CES) occurs when an atherosclerotic plaque causes small-vessel embolization, resulting in multi-organ damage. Although CES is pathologically characterized by an infiltration of eosinophils, the implication of the systemic inflammatory response represented by hypereosinophilia is unclear in clinical practice. Herein we present the case of a patient diagnosed with CES who developed multiple allergic organ injuries, including daptomycin-related dermatitis and later vancomycin-induced acute tubulointerstitial nephritis, which was successfully treated by the withdrawal of each medicine with or without corticosteroid therapy, one by one.Case presentationA 76-year-old Japanese man diagnosed with thoracic aneurysm rupture underwent total arch replacement through the open stent graft technique. Postoperatively, he developed methicillin-resistant Staphylococcus epidermidis bacteremia, which was treated with daptomycin. Subsequently, he presented with palpable purpura on both dorsal feet, erythema around his body, and hypereosinophilia. Daptomycin was replaced with vancomycin due to suspicion of drug-induced erythema. The erythema gradually faded. On nine days after vancomycin therapy, the systemic erythema rapidly reappeared followed by acute renal failure. The renal function decline prompted hemodialysis. A skin biopsy revealed cholesterol embolization, whereas a kidney biopsy revealed acute tubulointerstitial nephritis. After vancomycin discontinuation and initiation of systemic corticosteroid treatment, his kidney function was restored to the baseline level.ConclusionsThe present case highlights cholesterol embolization can cause allergic complications in addition to direct organ damage.