Vancomycin Duration Research Articles

P-815. Clinical Impact of BioFire® Blood Culture Identification 2 Implementation in Patients with Staphylococcal Bacteremia

Abstract Background The BioFire® Blood Culture Identification 2 (BCID2) PCR panel aids in rapid identification of blood pathogens, including coagulase-negative Staphylococci (CoNS) and methicillin susceptible Staphylococcus aureus (MSSA). BCID2 was implemented at all Hartford HealthCare hospitals in September 2022. The objective of this study was to evaluate how BCID2 impacted vancomycin use, clinical outcomes, and pharmacist intervention. Methods This was a multi-center, retrospective study of adult patients admitted to Hartford HealthCare hospitals with MSSA or CoNS positive blood cultures. The primary endpoint, days of vancomycin therapy, was compared between the pre- (3/7/22 – 9/7/22) and post-BCID2 periods (10/7/22 – 4/7/23). Secondary endpoints included duration of MSSA positive blood cultures, intensive care unit (ICU) length of stay, hospital mortality, and pharmacist interventions accepted. Results Of the 617 patients included in the primary analysis, MSSA bacteremia accounted for 37.0% (110/297) and 31.6% (101/320) of the patients in the pre- and post-BCID2 group, respectively (p=0.178). The median duration of vancomycin was 1.3 and 0.3 days in the pre- and post-BCID2 group, respectively (absolute difference, 1.0 days; p< 0.001). The duration of MSSA BSI was 3.1 and 2.4 days in the pre- and post-BCID2 group, respectively (absolute difference, 0.7 days; p=0.096). Hospital mortality was not different between periods [7.1% (21/297) vs 10.6% (34/320), p=0.16]. In patients with MSSA bloodstream infection (BSI), ICU LOS was 4.4 days shorter in the post-BCID2 period (7.8 vs 3.4 days, p< 0.001). Pharmacists successfully intervened to reduce vancomycin duration in 7.1% (21/297) and 16.3% (52/320) of patients in the pre- and post-BCID2 group, respectively (p< 0.001). Conclusion BCID2 implementation shortened the duration of vancomycin in patients with MSSA or CoNS bacteremia and facilitated pharmacist intervention to stop vancomycin in non-pathogenic CoNS positive blood cultures or switch to MSSA-targeted therapy in MSSA BSI. These data support BCID2 as a critical tool to improve appropriate antibiotic selection and shorten the time to safer and more effective treatment for patients with CoNS and MSSA bacteremia. Disclosures Joseph L. Kuti, PharmD, Abbvie: Advisor/Consultant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi Inc: Advisor/Consultant|Shionogi Inc: Grant/Research Support|Shionogi Inc: Honoraria|Venatorx: Grant/Research Support

P-1763. Implementation of a Pharmacy-based Automated MRSA PCR Screening Intervention to Guide Discontinuation of Vancomycin for Pneumonia

Abstract Background Vancomycin is administered for suspected methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in hospital settings, but is also associated with adverse effects, emergence of resistance, and requires lab and pharmacy monitoring. MRSA nares screening has excellent negative predictive value for MRSA pneumonia and results faster than culture. We sought to decrease vancomycin overuse by identifying patients at low risk for MRSA pneumonia using rapid polymerase chain reaction (PCR) as part of an automated pharmacy-based intervention. Methods We performed a retrospective cohort study of inpatients prescribed vancomycin for pneumonia at University Hospitals Cleveland Medical Center from November to May 2022 (pre-intervention) and November 2022 to May 2023 (post-intervention). In June 2022, we implemented a rapid MRSA PCR screen that was automatically added to orders when vancomycin was ordered for pneumonia. We compared median time to vancomycin discontinuation between the two groups. We performed a desirability of outcome ranking and response adjusted for duration of antibiotic risk (DOOR-RADAR) analysis, ranking patients according to duration of therapy within clinical categories to assess the effect of the intervention on patient-centered outcomes. Results We identified 127 pre-intervention and 125 post-intervention patients (Table 1). Median vancomycin order to discontinue time was lower in post-intervention patients, though this was meaningfully different only for patients whose PCR test was collected after the automated order was placed (41.75 vs 55 hours respectively, p = 0.035) (Table 2). Most patients in the post-intervention group with vancomycin duration >48 hours had delayed collection or were treated for other infections (Figure 1). The DOOR ranks for median time to discontinuation within clinical outcome categories were not meaningfully different between the two groups (p >0.05) (Table 2 and Figure 2) which may relate to sample size. Conclusion Vancomycin treatment duration was shorter in patients after a pharmacy-based automated MRSA PCR screening intervention when implemented efficiently. This research will guide future interventions including pairing automated rapid testing with active stewardship response. Disclosures Elie Saade, MD, MPH, FIDSA, Janssen Global Services: Advisor/Consultant|Janssen Global Services: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant Lisa M, Stempak, MD, Cytovale Inc.: Advisor/Consultant

P-421. Impact of Rapid Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Polymerase Chain Reaction (PCR) Screening on Duration of Vancomycin (Vanc) Therapy for Suspected Pneumonia (PNA) in Adult Patients (Pts) Admitted to the Trauma Intensive Care Unit (TICU)

Abstract Background At this institution on June 30, 2022, universal nasal decolonization with mupirocin ointment was replaced by nasal MRSA PCR assay screening at ICU admission to capture MRSA colonization and direct nasal decolonization. The aim of this study was to evaluate the impact of nasal MRSA PCR assay screening on duration of vanc for suspected PNA in adults admitted to the TICU.Table 1.Baseline and Treatment Characteristics Methods This single-center, retrospective cohort study compared pts from Jan - Jun 2022 (pre cohort) and Jan - Jun 2023 (post cohort). Pts ≥ 18 years of age admitted to the TICU that received empiric cefepime, meropenem, or piperacillin/tazobactam for suspected PNA documented on chest imaging were included. Pts who received vancomycin for a non-PNA indication, were previously treated for PNA during the admission, had structural lung disease, or had a pathogen identified on culture at the time of antibiotic (abx) initiation were excluded. The primary outcome was duration of vanc (hrs). Secondary outcomes included nasal MRSA PCR assay correlation with culture results from respiratory specimens, opportunities for vanc de-escalation based on negative nasal MRSA PCR assay within 36 hrs, ICU and hospital length of stay and mortality.Table 2.Primary and Secondary Outcomes Results 37 pts were included in each cohort. There were no significant differences in baseline characteristics (Table 1). 36 (97%) pts received vanc in the pre cohort compared to 26 (70%) pts in the post cohort (P < 0.01). The primary outcome (Table 2) of median vancomycin duration was 25 [14, 49] hrs in the pre cohort compared to 14 [0, 36] hrs in the post cohort (P = 0.02). Secondary outcomes are reported in Tables 2 and 3. The negative predictive value of the nasal MRSA PCR assay for PNA with MRSA was 100% in this study. MRSA was not identified on respiratory culture in either cohort.Table 3.Opportunities for De-escalation (Post Cohort) Conclusion Vanc usage and duration of therapy were significantly reduced after nasal MRSA PCR assay screening on ICU admission was implemented in the TICU. However, additional opportunities for improved stewardship of empiric initiation of vanc were identified based on the described vanc usage and lack of MRSA PNA. Disclosures John C. Williamson, PharmD, Armata Pharmaceuticals: Grant/Research Support|Blue Collar Vaccines and Therapeutics: Board Member|Blue Collar Vaccines and Therapeutics: Ownership Interest|Paratek Pharmaceuticals: Grant/Research Support|ST Pharm Co, Ltd: Grant/Research Support

Methicillin-Resistant Staphylococcus aureus Nasal Screening With Polymerase Chain Reaction for Early De-escalation of Empiric Vancomycin in the Treatment of Suspected/Confirmed Respiratory Infection in Critically Ill Patients.

Vancomycin empirically for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia coverage often is prolonged. With high negative predictive value for MRSA pneumonia, we evaluated the efficacy of MRSA nasal screening with polymerase chain reaction for early de-escalation of empiric vancomycin for treatment of respiratory infections in patients admitted to the intensive care units. The impact of MRSA nasal screening on early de-escalation of vancomycin for respiratory infections. A retrospective, single-center cohort study was conducted to evaluate the outcomes of vancomycin therapy in patients admitted to the intensive care units with diagnosis of pneumonia before (control group) and after (study group) implementation of MRSA nasal screening. The primary end point was the difference in duration of vancomycin drug therapy in patients with suspected/confirmed pneumonia between the control and study groups. Secondary end points included the number of vancomycin trough levels obtained, discordance between polymerase chain reaction and sputum culture results, and clinical outcomes. In total, 123 patients (control: n = 76; study: n = 47) were included. The median vancomycin duration in the control group and the study group was 73.3 hours (54.3-110.6) and 30.2 hours (20.3-39.7), respectively, P < 0.0001. The control group had 2.73 times (95% CI: 2.15-3.45, P < 0.0001) longer vancomycin duration than the study group. There was a significant difference in the number of trough levels obtained between the 2 groups. The median in the control and study groups were 1 (1-3) and 1 (0-1), respectively, P < 0.0001. There was no difference between groups for length of stay, 30-day readmission for MRSA infection, reinitiation of anti-MRSA therapy for infection, vancomycin-resistant enterococci infection within 30 days, acute kidney injury, and in-hospital all-cause mortality. The implementation of a MRSA nasal screening for critically ill patients treated with vancomycin for pneumonia resulted in a significantly shorter duration of vancomycin treatment without negatively affecting patient outcomes.

Oral vancomycin induced flushing syndrome in a multiple myeloma patient: A case report and review of the literature.

Patients with hematological malignancies are at high-risk of Clostridium difficile infection (CDI). Oral vancomycin is a first-line treatment for CDI. Vancomycin has been widely reported to induce flushing syndrome (also known as Red man syndrome), a well-known hypersensitivity reaction mostly occurs after intravenous administration. However, a few cases of flushing syndrome due to oral vancomycin have been reported. We reported a case of the 68-year-old male with Multiple Myeloma contracted suspected CDI during chemotherapy, oral vancomycin (125 mg po q6h) was initiated for CDI. Approximately 24 hours after receiving oral vancomycin, the patient developed vancomycin flushing syndrome with facial flushing and an erythematous rash on the abdomen and back, despite normal vancomycin duration and renal function (no obvious risk factors). The patient was diagnosed with Oral vancomycin induced flushing syndrome. The symptoms resolved after withdrawal of vancomycin and 4 days of treatment with loratadine. Oral vancomycin-induced flushing syndrome is a rare complication that can occur in patients with CDI despite the absence of obvious risk factors. The underlying mechanism of oral vacomycin-induced flushing syndrome may be direct activation of mast cells following mast cell degranulation and histamine release via the MRGPRX2 receptor. However, this is just speculation and there are insufficient data, particularly in vivo data, to draw any conclusions. For patients with risk factors such as gastrointestinal pathology and renal insufficiency, monitoring of vancomycin serum concentration, mast cell degranulation, histamine release, and MRGPRX2 levels is recommended to avoid vancomycin flushing Syndrome, and vancomycin can still be used under supervision.

Impact of Methicillin-Resistant Staphylococcus aureus Nasal Polymerase Chain Reaction Screening Tests on Duration of Vancomycin Therapy for Skin and Soft Tissue Infections.

Background: Recent literature demonstrated a 24-hour reduction in vancomycin duration of therapy (DOT) for skin and soft tissue infections (SSTIs) with a negative methicillin-resistant staphylococcus aureus (MRSA) nasal screening versus a positive nasal screening. Objective of this study was to investigate vancomycin DOT in patients with SSTIs who received MRSA nasal polymerase chain reaction (PCR) screening versus those who did not receive MRSA nasal PCR screening. Methods: A retrospective, multi-center, cohort study was completed in admitted adult patients on vancomycin for SSTI from 01/01/2020 to 09/30/2022. Hospital policy permits any clinician to order a MRSA nasal PCR screening test for various indications, including SSTIs, pneumonia and sepsis. Results: One-hundred-fifty-one patients were included, of which 71 had MRSA nasal PCR screening tests obtained, and 80 did not. The median vancomycin DOT in patients with MRSA nasal PCR screening tests was 19.9 versus 36.7 hours (P = .014) in patients without screening tests. Conclusion: Patients with SSTIs who receive MRSA nasal PCR screening tests have a shortened vancomycin DOT. These results contribute to current data in support of the efficacy and clinical utility of obtaining MRSA nasal PCR screening tests for SSTIs.

Impact of oral vancomycin treatment duration on rate of Clostridioides difficile recurrence in patients requiring concurrent systemic antibiotics.

There is a paucity of data guiding treatment duration of oral vancomycin for Clostridiodes difficile infection (CDI) in patients requiring concomitant systemic antibiotics. To evaluate prescribing practices of vancomycin for CDI in patients that required concurrent systemic antibiotics and to determine whether a prolonged duration of vancomycin (>14 days), compared to a standard duration (10-14 days), decreased CDI recurrence. In this retrospective cohort study, we evaluated adult hospitalized patients with an initial episode of CDI who were treated with vancomycin and who received overlapping systemic antibiotics for >72 hours. Outcomes of interest included CDI recurrence and isolation of vancomycin-resistant Enterococcus (VRE). Among the 218 patients included, 36% received a standard duration and 64% received a prolonged duration of treatment for a median of 13 days (11-14) and 20 days (16-26), respectively. Patients who received a prolonged duration had a longer median duration of systemic antibiotic overlap with vancomycin (11 vs 8 days; P < .001) and significantly more carbapenem use and infectious disease consultation. Recurrence at 8 weeks (12% standard duration vs 8% prolonged duration; P = .367), recurrence at 6 months (15% standard duration vs 10% prolonged duration; P = .240), and VRE isolation (3% standard duration vs 9% prolonged duration; P = .083) were not significantly different between groups. Discontinuation of vancomycin prior to completion of antibiotics was an independent predictor of 8-week recurrence on multivariable logistic regression (OR, 4.8; 95% CI, 1.3-18.1). Oral vancomycin prescribing relative to the systemic antibiotic end date may affect CDI recurrence to a greater extent than total vancomycin duration alone. Further studies are needed to confirm these findings.

160. Measuring the Impact of PCR-based MRSA Nares Screening on Vancomycin Use and Duration of Vancomycin Among Pneumonia Patients at an Academic Medical Center

Abstract Background The benefits of PCR-based MRSA nares screening for de-escalation of pneumonia therapy are well-established. In late 2022, UNCMC introduced a PCR-based MRSA nares screen for inpatient use, replacing a chromogenic culture-based screen. The improved turnaround time of the PCR-based test was hypothesized to increase adoption of screening for empirical de-escalation. This project assessed adoption of this diagnostic and measured impact on patients with pneumonia who comprise a cohort followed by the ASP using a visualization dashboard. Methods A report was generated of patients with admission ICD-10 codes compatible with pneumonia for January-March of 2022 (pre-PCR) and 2023 (PCR). Electronic medical records of included encounters were reviewed to collect respiratory culture data, validate vancomycin exposure days within the context of the patient’s renal function, and confirm presence of clinical pneumonia. For 2022 data, MRSA screen results were manually collected from the medical record, while for 2023 data, encounters were matched with MRSA PCR results. Fisher’s exact was used to analyze categorical data. Results 46 and 68 patients, respectively, were included for 2022 and 2023. There was a trend increase in the percentage of patients who were screened for MRSA (28% to 51%, p = 0.68; Table 1). Median turnaround time decreased from 2,022 min to 112 min. The frequency of respiratory sputum cultures, MRSA positivity, and empiric vancomycin therapy were similar. Median duration of vancomycin exposure decreased among all vancomycin recipients (3 to 2 days; Table 2). The percentage of vancomycin recipients who received just one day of coverage increased from 22% to 46%, a trend observed regardless of MRSA screening (Figure 1). Conclusion The PCR-based MRSA nares screen for inpatients with pneumonia has trended toward wider adoption compared to the prior screening method, and PCR has been associated with decreased durations of vancomycin therapy. However, similar trends were present in patients who did and did not undergo MRSA screening, suggesting both the new MRSA screen and broader institutional factors have contributed to a shift away from empirical anti-MRSA coverage for pneumonia. Disclosures All Authors: No reported disclosures

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

Agreement Between Two-Concentration and One-Concentration Area Under the Curve (AUC) Estimates When Using Bayesian Modeling to Dose Vancomycin in Patients With Obesity.

Vancomycin Bayesian modeling provides 24-hour area under the curve (AUC24) estimations. However, the agreement between two-concentration and one-concentration Bayesian estimates in patients with obesity is unknown. The purpose of this study was to determine the agreement between two-concentration and one-concentration Bayesian AUC24 estimates in patients with obesity receiving vancomycin. This retrospective within-subjects cohort study included patients with obesity and two vancomycin concentrations. The first concentration was hidden from dosing software to record the one-concentration AUC24. AUC24 estimates were categorized into 1 of 3 groups: <400, 400 to 600, or >600 mg*h/L. Patients were excluded for vancomycin duration less than 48 hours or renal dysfunction. The primary outcome was AUC24 agreement with two versus one concentration. Secondary outcomes included the AUC24 category, matching of AUC24 categorization, and correlation between two-concentration versus one-concentration AUC24. AUC24 estimate agreement was assessed by Bland Altman plot and bias via linear regression. Statistical analyses were performed using SPSS (version 20.0). A total of 31 patients were included. The mean difference in AUC24 between two versus one concentration was 11.4 mg*h/L (95% limits of agreement = -72 to 95 mg*h/L). Linear regression indicated the presence of proportional bias at higher AUC24 values (β = 0.16; P = 0.015). Matching of AUC24 categorization with two versus one concentration was 87% (27/31 patients). This study demonstrated overall agreement between AUC24 estimates when using two versus one vancomycin concentration in patients with obesity, though proportional bias was detected at higher AUC24. Future studies with larger sample sizes are needed to confirm these results.

A Large-Scale Multicenter Retrospective Study on Nephrotoxicity Associated With Empiric Broad-Spectrum Antibiotics in Critically Ill Patients

Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU. Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury? This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of< 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission. Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n= 27,459; vancomycin and cefepime, n= 6,371; vancomycin and meropenem, n= 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95%CI, 1.25-1.49]; dialysis: OR, 1.28 [95%CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95%CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy. VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU.

Safety and Feasibility Assessment of a Pharmacy-Driven AUC/MIC Vancomycin Dosing Protocol in a Multicenter Hospital System.

Vancomycin is used for Gram-positive infections, including methicillin-resistant Staphylococcus aureus. The 2020 vancomycin guidelines described by M. J. Rybak, J. Le, T. P. Lodise, D. P. Levine, et al. (Am J Health Syst Pharm 77:835-864, 2020, https://doi.org/10.1093/ajhp/zxaa036) provided an update on vancomycin dosing, which recommended an optimal area under the concentration-time curve over 24 h to MIC (AUC/MIC) target of 400 to 600. In 2021, a pharmacy-driven AUC/MIC vancomycin dosing protocol was implemented across 12 Sentara Health System hospitals. The primary objective of this study was to assess if the pharmacy-driven AUC/MIC vancomycin dosing protocol led to fewer acute kidney injury (AKI) events than trough-based dosing. Secondary objectives included vancomycin duration, hospital length of stay, administered vancomycin dose during admission, vancomycin labs drawn during standard lab times, and cost. AKI was assessed in two separate ways: (i) modified AKIN (Acute Kidney Injury Network) criteria and (ii) a modified version from the vancomycin guidelines. Inferential statistics were used to analyze the results of this retrospective study. Per the AKIN definition, the rates of AKI were 13.9% (349/2,507) in the trough-based group and 14.9% (369/2,471) in the AUC/MIC-based group (P = 0.309). Per the definition of the vancomycin guidelines, the rates of AKI were 6.7% (169/2,507) in the trough-based group and 7.6% (187/2,471) in the AUC/MIC-based group (P = 0.258). A total of 52% (2,679/5,151) of vancomycin labs were obtained during standard lab times in the AUC group and 24% (1,144/4,766) in the trough group (P < 0.05). There was no difference in AKI events between AUC and trough dosing. Use of contrast dye may confound these results. AUC/MIC dosing was associated with more lab draws during standard times, a larger number of labs drawn per person, and less total use of vancomycin. IMPORTANCE In this article, we report that there were no differences in rates of acute kidney injury between trough-based vancomycin dosing and AUC/MIC-based vancomycin dosing across 12 hospitals. AUC/MIC dosing resulted in more vancomycin lab draws during standard lab draw times compared to trough dosing, thus making it more convenient for health care personnel. This study includes all uses for vancomycin, including empirical use, and all patient severity levels. Therefore, this research reflects real-world use of vancomycin in hospitals. AUC/MIC dosing is supported by various infectious disease societies. However, the feasibility of incorporating AUC/MIC dosing in hospitals is undetermined. This study is unique in that it includes hospitals of various sizes (small community hospitals and an academic teaching hospital), and it includes a feasibility component. Therefore, this study has broad applicability to other hospitals across the United States. This original research includes the clinical application of vancomycin in a multicenter health system.

Comparative renal risk of long-term use of beta-lactams in combination with vancomycin across the continuum of care.

Data are controversial regarding nephrotoxicity risk with vancomycin plus piperacillin-tazobactam (VPT) compared to vancomycin alone or in combination with other beta-lactams (BLs) in acute care use. Furthermore, data are lacking on the incidence of acute kidney injury (AKI) with long-term use of VPT including outpatient parenteral antimicrobial therapy (OPAT). This retrospective study included 826 adult patients on an intravenous vancomycin plus BL for ⩾2 weeks, including cefepime, piperacillin/tazobactam, ertapenem, or meropenem, from August 2017 to January 2022. The primary outcome was incidence of AKI. Univariate and multivariable Cox proportional hazard regression analyses were conducted to adjust for confounding variables. A secondary analysis based on the propensity score (PS)-matched cohort was performed. AKI occurred in 14.4% of patients in the VPT group (n = 15/104) compared to 5.5% in the other BL group (n = 40/722) (p < 0.001). Average time to AKI from start of combination therapy was 9.4 (1.7-12.0) days in the VPT group and 10.9 (5-22.7) days in the other BL group (p = 0.20). The median duration of vancomycin and BL in the overall cohort was approximately 1 month. Beyond BL selection, patient characteristics were not associated with AKI other than the receipt of concomitant acyclovir [hazard ratio (HR) 2.48 (95% confidence interval (CI): 1.33-4.65), p = 0.004]. In the PS-matched cohort, AKI occurred in 14.4% of patients in the VPT group (n = 15/104) and 5.3% in the other BL group (n = 11/208) (p = 0.006). Receipt of VPT [HR: 2.55 (1.36-4.78), p = 0.004] and acyclovir [HR: 2.38 (1.19-4.74), p = 0.014) remained significantly associated with AKI in the multivariable model. Clinicians should exercise caution when using VPT for >2 weeks, including in the OPAT setting, even when no renal dysfunction is observed during the initial week of combination therapy.

176. Evaluation of the Predictive Value of Methicillin-Resistant Staphylococcus aureus (MRSA) Nares Polymerase Chain Reaction (PCR) Screening within Hospitalized Patients

Abstract Background While MRSA nares PCR screening utilization has established evidence for de-escalation of anti-MRSA agents in pneumonia, its utility in other sites of infection is not well studied. The purpose of this study was to evaluate the utility of MRSA nares PCR screening within a wide range clinical specimens and its impact on antimicrobial stewardship. Methods This retrospective study was conducted at a 446-bed academic medical center. Patients ≥ 18 years old with an in-house MRSA nares PCR ordered between 1 November 2021 and 1 February 2022 were included in the primary analysis. Negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity were calculated using cultures obtained within 7 days of nares screening. Vancomycin duration, de-escalation, and incidence of acute kidney injury were collected pre- and post- implementation of the in-house MRSA PCR screening. The pre-intervention cohort observed patients admitted from 1 November 2020 to 1 February 2021 screened by send out MRSA nares PCR. Results At baseline, patients were a mean age of 55 years old, 55% black, and required ICU care in 50% of cases. A total of 665 cultures from 308 patients were included in the primary analysis (131 respiratory, 282 blood, 154 urine, 61 wound, 22 sterile fluid, 15 bone, and 12 spinal fluid specimens). The overall NPV of the MRSA nares PCR screening was 99.8% and the PPV was 21.1%. The sensitivity and specificity were 96.8% and 81.67%, respectively. Duration of vancomycin was a median of 3 days in both the pre- and post- intervention cohorts. However, rates of vancomycin de-escalation increased at day 3 from 31.5% to 48.1% and at day 5 from 69.9% to 80.0% post implementation on an in-house MRSA PCR screening. Incidence of acute kidney injury decreased from 45.2% to 21.6%. Conclusion Based on its high NPV among cultures of different sites, MRSA nares PCR screening may be utilized to de-escalate anti-MRSA agents within tertiary care facilities. Disclosures All Authors: No reported disclosures.

913. Impact of BioFire® FilmArray® Blood Culture Identification Panels on Time to Optimal Antimicrobial Therapy

Abstract Background Bloodstream infections are associated with significant morbidity, mortality, and costs. Timely initiation of effective treatment is required for optimal outcomes. Conventional microbiological techniques require 72 hours for organism identification; however, rapid blood culture identification (BCID) polymerase chain reaction (PCR) panels have expedited this process. At Atlantic Health System, the BioFire® FilmArray® BCID panel was implemented June 2020 (BCID1), with subsequent upgrade to BCID2 March 2021. Notable features of the BCID2 panel include speciation of Enterococcus spp. and the addition of the CTX-M target. The purpose of this study is to assess time to optimal therapy (TTOT) with and without the BCID platforms for select organisms. Table 1:Select Primary and Secondary Endpoints Methods This retrospective study of hospitalized, adult patients was conducted at two community teaching hospitals from 5/2019 to 12/2021. Patients with a blood culture positive for Enterococcus faecalis, E. faecium, Proteus spp., Escherichia coli, or non-aerogenes Klebsiella spp. were included. Patients with polymicrobial or presumed polymicrobial source of bacteremia, recent positive blood cultures, PCR not performed in BCID arms, or who were deceased/comfort care at time of Gram stain were excluded. The primary endpoint was TTOT. Secondary endpoints included time to effective therapy, duration of vancomycin, therapy modification 24 hours after Gram stain result, and length of stay. All analyses compared PreBCID to either BCID1 or BCID2 arm. Results Three hundred patients (100 per arm) were included. Patient characteristics were similar across study arms. The median Pitt Bacteremia Score was 1, the most common organism identified was E. coli (65%), the most common source of bacteremia was genitourinary (65%), and 11% of isolates produced ESBL. TTOT (days) was similar in PreBCID compared to BCID1 and BCID2 [(2.48 vs. 2.65, p=0.10); (2.48 vs. 2.37 days, p=0.27)]. TTOT was significantly longer in the gram-negative subgroup of the BCID1 arm compared to PreBCID (2.62 vs 1.85 days, p=0.03). See Table 1 for full analyses. Conclusion Implementation of the BCID panels did not reduce TTOT in select organisms at our institution. Barriers to benefit may include limited education and lack of formal antimicrobial stewardship team involvement. 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.

188. Opportunities for antimicrobial stewardship: Time to optimal therapy and vancomycin use in gram-positive and contaminated blood cultures before and after implementation of rapid blood culture diagnostic testing

Abstract Background Rapid molecular diagnostic tests improve time to organism identification and may expedite antimicrobial de-escalation. Through faster detection of contaminated samples, rapid blood culture identification (BCID) should also reduce unnecessary antibiotic use. BioFire FilmArray BCID was implemented in July 2019 at a community hospital. This study compared antimicrobial use for gram-positive blood cultures before and after BCID implementation to identify areas for further antimicrobial stewardship intervention. Methods This retrospective cohort study evaluated adult patients at a 450-bed community hospital with gram-positive blood culture results between February and June 2018 and 2019 (pre-and post-BCID). Patients were excluded for polymicrobial bacteremia, pregnancy, or expiration/hospice status before blood culture positivity. The primary outcome was time to optimal therapy (TTOT) for bacteremia, defined as time to antimicrobial de-escalation, discontinuation, or result for untreated contaminated cultures. Time to organism identification, receipt of optimal therapy, and vancomycin duration were also evaluated, in addition to subgroup analysis of contaminated cultures (identified by microbiology comment or physician note). Results Of the 232 patients, median age was 70 years and 54.3% were male. Coagulase-negative staphylococci was most commonly isolated (n=104, 45%) and contamination rate was 53.4%. Median TTOT improved from 53.3 vs 28 hours, p&amp;lt; 0.001 in pre- vs post-groups, respectively, and optimal therapy selection increased from 83% to 93%, p=0.028. Median time to organism identification was 60.2 vs 23.5 hours, p&amp;lt; 0.001. Median duration for vancomycin (35.1 vs 25.2 hours, p=0.231) and overall antimicrobial duration did not differ between groups. Among contaminated blood cultures, TTOT improved (54 vs 27.3 hours, p&amp;lt; 0.001) and vancomycin median duration decreased (27.5 vs 16.6 hours, p=0.253). Conclusion Rapid BCID significantly improved TTOT, resulting in improved rates of optimal therapy and an observed reduced vancomycin duration. High rates of contaminated blood cultures identified opportunities for coordination with antimicrobial stewardship to reduce contamination rates and improve antimicrobial use. Disclosures All Authors: No reported disclosures.

P17 Vancomycin therapeutic drug monitoring—a call for change?

ObjectivesDespite the widespread use of vancomycin, optimization of dosing can be difficult. Increased vancomycin concentrations are associated with nephrotoxicity, while subtherapeutic levels may lead to inadequate antibacterial therapy and risk development of antimicrobial resistance. Recent guidelines have recommended the use of loading doses and switching to AUC24 TDM, targeting an AUC24:MIC ratio of 400–600 μg·h/mL to minimize toxicity while maintaining similar effectiveness for the treatment of serious infections. We aimed to review adherence to current local vancomycin dosing and conventional trough monitoring guidelines, as well as record time to, and factors related to, achieving target vancomycin troughs.MethodsFifty consecutive electronic prescriptions were screened for IV vancomycin use in treatment of active infections in a single acute Trust during April/May 2021. These were cross-referenced with microbiological, clinical and biochemical data from patient records. Variables were analysed by parametric or non-parametric methods on the basis of their normality distribution using GraphPad Prism.ResultsForty-one patients were included of which 39 had a vancomycin level measured. Mean age was 57 years (range 19–88) and BMI 28 (range 17–44). Nineteen had unstable renal function, including one receiving intermittent haemodialysis. Median CLCR was 95 mL/min (IQR 66–129). Indications were included on the prescription for 26. Median duration of vancomycin was 4 days (range 2–12), and half of patients ultimately switched therapy to an alternate agent . Target troughs were documented in 29 (70%), 9 of which had a target trough ≥15 μg/mL. Twenty-four had positive microbiology samples, 19 of which were organisms against which vancomycin would have expected activity. Five (13%) failed to achieve trough levels >10, 6/39 (15%) achieved troughs of 10–15, 13/39 (33%) 15–20, and 15/39 (38%) had troughs of >20 μg/mL (Figure 1). Where it was achieved, the median time to level ≥10 μg/mL was 46 h (range 11–202) and time to level ≥15 μg/mL was 68 h (range 18–243). Twenty-five (60%) patients required titration above the currently recommended initial dose, and 22 required doses of 1500 mg twice daily or higher. BMI did not correlate with vancomycin level achieved.Figure 1.Vancomycin trough ranges.ConclusionsA significant proportion of patients with serious infections fail to achieve or have a considerable delay in achieving therapeutic vancomycin trough. An even greater proportion have troughs above target and are at risk of nephrotoxicity. These findings support a potential switch to more personalized regimens using loading doses and AUC24 monitoring where vancomycin is the drug of choice. This would complement other stewardship measures to limit overall vancomycin use, achieve earlier and more complete source control, and optimize use of alternative antimicrobial therapies with more predictable PK/PD.

Impact of Empiric Linezolid for Necrotizing Soft Tissue Infections on Duration of Methicillin-Resistant Staphylococcus aureus-Active Therapy

Background: Necrotizing soft tissue infections (NSTIs) require prompt surgical debridement and antimicrobial therapy. Indicated antimicrobial therapy involves broad-spectrum coverage against common pathogens and toxin inhibition. Linezolid provides both methicillin-resistant Staphylococcus aureus (MRSA) coverage and toxin inhibition, however, there is limited evidence evaluating its role in empiric treatment. The purpose of this study was to evaluate the impact of empiric linezolid use for NSTIs on the total duration of MRSA-active therapy. Patients and Methods: This retrospective, single-center study included adult surgical intensive care unit (ICU) patients treated with empiric vancomycin and clindamycin or linezolid along with gram-negative and anaerobe coverage for NSTIs. The primary end point of this study was the duration of MRSA-active therapy. Secondary end points included ICU and hospital length of stay (LOS; days), new-onset acute kidney injury (AKI), and Clostridioides difficile infection (CDI). Results: There were 21 patients in the vancomycin/clindamycin cohort and 28 patients in the linezolid cohort. The average duration of vancomycin was 3.9 days versus 2.9 days of linezolid (p = 0.04). The average hospital LOS for the vancomycin/clindamycin cohort was somewhat longer than the linezolid cohort, although the difference was not statistically significant (p = 0.07), and the incidence of new-onset AKI during hospitalization was higher in the vancomycin/clindamycin cohort (38.1% vs. 0%; p < 0.001). No differences were observed for ICU LOS or CDI. Conclusions: Empiric linezolid use for NSTI was associated with one less day of MRSA-active therapy and lower incidence of new-onset AKI during hospitalization. Linezolid was a safe and effective alternative to vancomycin/clindamycin for empiric treatment of NSTIs.

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.