anti-MRSA Therapy Research Articles

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.

Impact of Continuous Infusion Meropenem PK/PD Target Attainment on C-Reactive Protein Dynamics in Critically Ill Patients With Documented Gram-Negative Hospital-Acquired or Ventilator-Associated Pneumonia.

Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of antibiotics including C-reactive protein (C-RP) dynamics could be helpful in predicting the efficacy of antimicrobials. We developed a PK/PD model for assessing the impact of continuous infusion (CI) meropenem PK/PD target attainment on C-RP dynamics in critically ill patients with documented Gram-negative hospital- (HAP) or ventilator-acquired pneumonia (VAP). Patients were grouped according to the type of antibiotic treatment received [meropenem monotherapy; meropenem plus empirical anti-MRSA (methicillin-resistant Staphylococcus aureus) therapy; meropenem in combination with another anti-Gram-negative active agent; meropenem plus a targeted anti-MRSA therapy]. A one-compartment population PK model of CI meropenem was developed by including all patients. A full C-RP production inhibition model was developed for fitting the PD data by including only patients receiving meropenem monotherapy or meropenem plus empirical anti-MRSA therapy. Monte Carlo simulations explored the relationship between the type of PK/PD target attainment of CI meropenem, defined as optimal (steady-state plasma concentration [Css] to minimum inhibitory concentration [MIC] ratio = 4-8), quasi-optimal (Css/MIC = 1-4) and sub-optimal (Css/MIC < 1) and the magnitude of C-RP production inhibition over time. A total of 64 patients providing 211 meropenem concentrations were included in the PK analysis, whereas 47 patients providing 328 C-RP data were included in the PD model. Simulations showed that optimal PK/PD target attainment was associated with the highest and most rapid C-RP production inhibition (44% and 56% at days 2 and 4, respectively). Conversely, sub-optimal PK/PD target attainment was shown to be almost ineffective (< 5% at day 4 and < 10% at day 10). Our PK/PD model predicted that attaining optimal PK/PD target with CI meropenem may grant prompt and intense C-RP decrease among critically ill patients receiving targeted monotherapy for Gram-negative HAP/VAP, thus anticipating efficacy.

Impact of rapid blood culture identification PCR panel on optimal antibiotic use in methicillin-susceptible Staphylococcus aureus bacteremia.

In this retrospective study of 200 patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, the implementation of the BioFire® blood culture identification polymerase chain reaction (PCR) panel was associated with a decreased time to optimal MSSA antibiotic therapy and shorter durations of empiric anti-MRSA antibiotic therapy and bacteremia. The findings demonstrate the significant role of rapid PCR testing and routine stewardship review in optimizing antimicrobial therapy and management of MSSA bacteremia.

Rapid de-escalation of anti-MRSA therapy guided by S. aureus nares screening for patients with pneumonia: protocol of a randomized controlled trial (SNAP study).

The current Infectious Disease Society of America and American Thoracic Society (IDSA/ATS) guidelines recommend linezolid or vancomycin as an empiric treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in hospitalized patients with specific risk factors,. A nasal PCR-assay for MRSA, with its high negative predictive value, can guide a rapid antibiotic de-escalation avoiding unnecessary anti-MRSA treatment. The indiscriminate use of these drugs has contributed to the emergence of resistant S. aureus strains leading to adverse effects without any survival benefit, increasing hospital stays and associated costs. Aim of the study is the use of this diagnostic tool to reduce empirical anti-MRSA treatment duration in pneumonia, shortening antimicrobial therapy days while measuring in-hospital mortality, length of stay and adverse drug event incidence. It is a prospective, randomized single-center controlled trial planned to be conducted in the Azienda Consorziale Policlinico di Bari. The research project will have a duration of 12 months following the approval of the Ethical Committee of the University of Bari. The minimum sample size is 38 patients per group, for a total of 76 subjects, calculated assuming a standard deviation of 10, a power of 90%, a type I error of 5% and a 10% drop-out rate. We will enroll eligible patients ensuring their evidence-based management according to guidelines, we will perform a nasal swab for MRSA in patients in the experimental group and discontinue the empirical anti-MRSA therapy if the nasal swab result is negative. For both arms, follow-up visits will be on day 2, 5, 7, 14, and 28 relatives to the enrollment visit (day 0). Data will be collected on the clinical course of pneumonia and laboratory tests. Our study will provide evidence on the duration (in days) of the antibiotic intake as a primary outcome of the study. Secondary outcome measures include in-hospital mortality, the length of stay and days of mechanical ventilation (in VAP), and the incidence of adverse events related to the administration of the therapy. https://classic.clinicaltrials.gov/ct2/show/NCT06238297, identifier NCT06238297.

Pediatric Clinical Outcomes of Nasal Methicillin-resistant Staphylococcus aureus Polymerase Chain Reaction Utilization.

Methicillin-resistant Staphylococcus aureus (MRSA) is a clinical challenge in selecting empiric antimicrobials for pediatric infections. We implemented nasal MRSA polymerase chain reaction (nMRSA PCR) screening as a diagnostic tool and evaluated its impact on empiric antibiotic use and clinical outcomes. A retrospective single-center study of patients hospitalized with infections who were empirically prescribed anti-MRSA antibiotics was conducted prior to and following the initiation of nMRSA PCR screening. Electronic medical records, pharmacy data and bacterial cultures results were reviewed. Predictive values of nMRSA PCR testing were calculated and the duration of anti-MRSA empiric therapy and clinical outcomes preimplementation and postimplementation were compared. During the preimplementation period, there were 382 distinct episodes (294 unique patients) that met the inclusion criteria and during post-nMRSA PCR implementation, 394 episodes (360 unique patients) were identified. The median time to discontinuation of anti-MRSA antibiotics and proportion of patients prescribed anti-MRSA antibiotics at discharge were significantly lower in postimplementation compared with preimplementation period; 48 versus 56 hours, P < 0.001 and 20.1% versus 40.3%, P < 0.001, respectively. The negative and positive predictive values of nMRSA PCR compared to clinical culture results were 95.6% and 51.2%, respectively. Predefined adverse outcomes were documented in 11 patients who had early anti-MRSA discontinuation with negative nMRSA PCR results but only 3 were restarted on anti-MRSA treatment and none grew MRSA in clinical cultures. Shortened anti-MRSA antibiotic duration, high negative predictive value and low adverse events provide promising evidence that nMRSA PCR is an effective, rapid antimicrobial stewardship tool for hospitalized children.

Persistent methicillin-resistant Staphylococcus aureus (MRSA) nares test positivity during initial days of systemic antistaphylococcal antimicrobial therapy

The typical duration of positive nucleic acid tests for methicillin-resistant Staphylococcus aureus (MRSA) in the nares of patients receiving systemic anti-MRSA antimicrobials is unknown. In this study, hospitalized adult patients with an initial positive MRSA nares nucleic acid test prescribed systemic anti-MRSA antimicrobials had follow-up testing done 48 to 96hours later. A positive follow-up test was detected in 100/113 (88.5%), indicating that MRSA nares DNA tests still have utility for screening after patients have initiated anti-MRSA therapy.

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 &lt; 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 &lt; 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.

Guideline-unjustified inpatient therapy for non-ICU patients with community-acquired pneumonia (CAP) at 105 Veterans Affairs

Background: CAP is often inappropriately treated with agents active against multidrug-resistant organisms (MDRO; methicillin-resistant S. aureus [MRSA] and P. aeruginosa [PSA]) and for prolonged duration. We assessed the relationship between antibiotic use with ATS/IDSA guideline-unjustified empiric and definitive MDRO therapy and prolonged duration in non-ICU inpatients with CAP at 105 VA Medical Centers. Methods: From VA Corporate Data Warehouse data, we identified patients with discharge ICD-10-CM codes consistent with CAP from 1/2022-3/2023, excluding cases with 14 days of antibiotic therapy, ICU admission, concurrent infections, or severe immunocompromise. We considered as jultified empiric (≤third day of hospitalization) therapy: anti-MRSA therapy for patients with prior positive MRSA cultures, anti-PSA therapy for patients with prior positive PSA cultures, and both anti-MRSA &amp; anti-PSA therapy in patients with severe pneumonia and intravenous antibiotics in the prior 3 months. Definitive (&gt;third day of hospitalization) anti-MDRO therapy was considered unjustified in patients who had achieved clinical stability and whose cultures did not grow MRSA or PSA. Prolonged duration (&gt;6 days of therapy) was unjustified if patients were clinically stable or discharged by day 5. Results: The median age of the 29,260 patients was 75 (IQR 69,81); 4.6% were women. While 33% and 22% of patients received empiric or definitive MDRO therapy, such therapy was jultified in 12% and 0.5%, respectively. Median facility use of empiric and definitive MDRO therapy was 31% (IQR 25%,38%) and 20% (15%,23%), respectively (Figure 1); this use was unjustified in 89% (85%,93%) and 100% (100%,100%), respectively. Pearson’s correlation coefficient between MDRO therapy and rates of unjustified empiric and definitive MDRO therapy for CAP was 0.54 and 0.61, respectively (Figure 2). Although 99% of patients were discharged or stable by day 5, 42% received prolonged therapy. The median frequency of prolonged therapy was 39% (33%,48%); facility rates of prolonged therapy had a correlation of 0.56 with total antibiotic use and 0.46 with MDRO therapy (Figure 3). Discussion: Based on electronic documentation, we identified 1) substantial opportunities to reduce unjustified anti-MDRO therapy and the duration of therapy in hospitalized non-ICU patients with CAP; 2) a moderate correlation of unjustified anti-MDRO therapy with increased MDRO antibiotic use and of prolonged duration of therapy with increased total and MDRO antibiotic use. The correlation of lower quality prescribing with increased antibiotic use provides further impetus for tools such as dashboards (Figure 4) to assist antibiotic stewards in designing and monitoring interventions to reduce unjustified therapy.

Assessing the Predictive Value of Methicillin-Resistant Staphylococcus aureus Nares Colonization Among Transplant Recipients and Patients With Neutropenia.

Methicillin-resistant Staphylococcus aureus (MRSA) nares screening has been shown to be a powerful antibiotic stewardship tool for MRSA infections within 7 days of screening across a variety of anatomical locations given the high negative predictive value (NPV). However, the utility outside of 7 days and among transplant recipients and patients with neutropenia is less clear. This was a retrospective cohort study across Veterans Affairs medical centers in the United States from 1 January 2007 to 1 January 2023 of patients tested for MRSA colonization and who had a subsequent positive bacterial culture within 28 days of MRSA sc---reening. Sensitivity, specificity, positive predictive value, and NPV were calculated across different time points and anatomical culture locations. The cohort consisted of 686 174 patients, 6 277 437 MRSA nares tests, and 2 446 766 positive bacterial cultures within 28 days of MRSA testing. The NPV of MRSA nares screening for ruling out a MRSA infection within 28 days was 95.8% across all anatomical culture sites. The NPV was 97.9% among patients with neutropenia and 97.5% in solid organ and hemopoietic stem cell transplant recipients. MRSA nares screening can reliably be used for de-escalation of anti-MRSA therapy within 28 days of bacterial culture for all patients, including solid organ and hematopoietic transplant recipients and patients with neutropenia.

Trends in Empiric Broad-Spectrum Antibiotic Use for Suspected Community-Onset Sepsis in US Hospitals

Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time. To describe trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis. This cross-sectional study used clinical data from adults admitted to 241 US hospitals in the PINC AI Healthcare Database. Eligible participants were aged 18 years or more and were admitted between 2017 and 2021 with suspected community-onset sepsis, defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration on admission. Empiric anti-methicillin-resistant Staphylococcus aureus (MRSA) and/or antipseudomonal β-lactam agent use. Annual rates of empiric anti-MRSA and/or antipseudomonal β-lactam agent use and the proportion that were likely unnecessary in retrospect based on the absence of β-lactam resistant gram-positive or ceftriaxone-resistant gram-negative pathogens from clinical cultures obtained through hospital day 4. Annual trends were calculated using mixed-effects logistic regression models, adjusting for patient and hospital characteristics. Among 6 272 538 hospitalizations (median [IQR] age, 66 [53-78] years; 443 465 male [49.6%]; 106 095 Black [11.9%], 65 763 Hispanic [7.4%], 653 907 White [73.1%]), 894 724 (14.3%) had suspected community-onset sepsis, of whom 582 585 (65.1%) received either empiric anti-MRSA (379 987 [42.5%]) or antipseudomonal β-lactam therapy (513 811 [57.4%]); 311 213 (34.8%) received both. Patients with suspected community-onset sepsis accounted for 1 573 673 of 3 141 300 (50.1%) of total inpatient anti-MRSA antibiotic days and 2 569 518 of 5 211 745 (49.3%) of total antipseudomonal β-lactam days. Between 2017 and 2021, the proportion of patients with suspected sepsis administered anti-MRSA or antipseudomonal therapy increased from 63.0% (82 731 of 131 275 patients) to 66.7% (101 003 of 151 435 patients) (adjusted OR [aOR] per year, 1.03; 95% CI, 1.03-1.04). However, resistant organisms were isolated in only 65 434 cases (7.3%) (30 617 gram-positive [3.4%], 38 844 gram-negative [4.3%]) and the proportion of patients who had any resistant organism decreased from 9.6% to 7.3% (aOR per year, 0.87; 95% CI, 0.87-0.88). Most patients with suspected sepsis treated with empiric anti-MRSA and/or antipseudomonal therapy had no resistant organisms (527 356 of 582 585 patients [90.5%]); this proportion increased from 88.0% in 2017 to 91.6% in 2021 (aOR per year, 1.12; 95% CI, 1.11-1.13). In this cross-sectional study of adults admitted to 241 US hospitals, empiric broad-spectrum antibiotic use for suspected community-onset sepsis accounted for half of all anti-MRSA or antipseudomonal therapy; the use of these types of antibiotics increased between 2017 and 2021 despite resistant organisms being isolated in less than 10% of patients treated with broad-spectrum agents.

297 Antibiotic prescribing for inpatients with community-acquired bacterial pneumonia (CABP) due to methicillin-resistant Staphylococcus aureus (MRSA) in the All of Us database: Are there differences by age, sex, race, and ethnicity?

OBJECTIVES/GOALS: The purpose of this work is to assess antibiotic prescribing for inpatients with community-acquired bacterial pneumonia (CABP) due to methicillin-resistant Staphylococcus aureus (MRSA) in the All of Us database. The goal of this research is to determine if different subgroups are more or less likely to receive anti-MRSA antibiotics. METHODS/STUDY POPULATION: This is a retrospective cohort study of inpatients with CABP due to MRSA from 2/1/2011 to 7/1/2022 in the All of Us database. Cases will be excluded for other treatment settings, other pathogens, and other types of pneumonia. Patients will be stratified by age, sex, race, and ethnicity. The proportion of patients who received anti-MRSA antibiotic therapy will be compared within groups with the chi-square statistic. Significant associations between patient characteristics and anti-MRSA prescribing (p &lt; 0.05) will be assessed using multivariate logistic regression, with subgroup as the independent variable, anti-MRSA prescribing as the dependent variable, and divergent baseline characteristics as potential confounders. Odds ratios (OR) and 95% confidence intervals (95% CI) will be calculated. RESULTS/ANTICIPATED RESULTS: Previous research by our group has demonstrated differences in guideline-concordant, empiric antibiotic prescribing, for inpatients with CABP in the All of Us database; however, guideline-concordant empiric antibiotics for CABP do not routinely cover for MRSA. Anti-MRSA antibiotics are recommended if the patient has known MRSA or risk factors for MRSA. Investigations of disparity in anti-MRSA prescribing have been limited, especially since the abandonment of the healthcare-associated pneumonia (HCAP) categorization. Since the All of Us database contains information on CABP pathogens, we can study sub-types of CABP; therefore, we now hypothesize that the proportion of inpatients who received anti-MRSA antibiotics for CABP, due to MRSA, in the All of Us database, will differ by age, race, sex, and ethnicity. DISCUSSION/SIGNIFICANCE: This is one of the first studies to evaluate antibiotic prescribing for CABP due to MRSA in the All of Usdatabase. Identifying and understanding differences in care, such as possible discrepancies in anti-MRSA prescribing by age, sex, race, or ethnicity, is essential to develop targeted interventions to address disparities in health outcomes.

An NIR-II-enhanced nanozyme to promote wound healing in methicillin-resistant Staphylococcus aureus infections

Deep tissue bacterial infections, especially methicillin-resistant Staphylococcus aureus (MRSA) infections, pose challenges to clinical therapy due to their low debridement efficiency and relapsing. Molybdenum disulfide (MoS2) is used in the antibacterial field as a classic photothermal agent (NIR-I) with good biocompatibility. However, due to its limited NIR-I tissue penetration ability and single treatment mode, MoS2 has poor therapeutic effects on deep tissue infection. Herein, we prepared a defect-type hybrid 2H-MoS2 nanozyme (MoWS2) using hydrothermal method fabricate the MoWS2 composite, which is a new antibacterial strategy involving photothermal and enzyme catalysis, and further enhances the activity of the nanozyme through overheating. The regulation of 2H-MoS2 defects through tungsten ion doping endows MoWS2 with better near-infrared two-region absorption (NIR-II) and enzyme catalytic performance. Antibacterial activity experiments in vitro have shown that MoWS2 can achieve efficient bactericidal activity and biofilm clearance through hyperthermia and reactive oxygen species (ROS). Deep MRSA infection experiments have shown that MoWS2 rapidly removes bacteria from subcutaneous infected tissues through photothermal therapy (PTT) and chemodynamic therapy (CDT), accelerates the dissipation of abscesses, and promotes the healing of infected wounds. Additionally, the versatile treatment mode of MoWS2 was further confirmed through tissue sectioning and immunofluorescence staining analysis. Overall, these results provide a feasible approach for achieving efficient treatment of deep tissue infections through tungsten ion doping to regulate defective 2H-MoS2. Statement of significanceThe photothermal effect of MoS2 nanosheets in the NIR-I (650-900 nm) window in anti-MRSA therapy is considered to be highly reliable and efficient in PTA. However, most of the developed PPT therapies or antimicrobial systems based on PTT therapies developed with 1T-MoS2 have in vivo sterilization temperatures of more than 55°C, which have the risk of damaging the normal tissues of the skin. In this study, we prepared W@MoS2 with a good photothermal effect (36.9%) in the NIR-II window and good peroxidase-like activity. The combined effect of PTT and CDT has a stronger bactericidal effect while avoiding high-temperature damage, which makes the W@MoS2 material more advantageous in terms of antimicrobial effect.

154. Impact of Rapid Blood Culture Identification (BCID) PCR Panel on Optimal Antibiotic Use in Methicillin-Susceptible Staphylococcus aureus (MSSA) Bacteremia

Abstract Background Optimal anti-MSSA antibiotic choices are nafcillin, oxacillin, and cefazolin. Vancomycin, often used empirically for S. aureus infections, and other broad-spectrum β-lactam antibiotics, such as piperacillin/tazobactam and ceftriaxone, are linked with suboptimal outcomes compared to anti-MSSA β-lactam therapy. BCID PCR testing allows for faster pathogen identification, which may improve antibiotic use and clinical outcomes. The objective of this study was to assess the impact of BioFire BCID PCR panel implementation on antibiotic use and clinical outcomes in patients with MSSA bacteremia. Methods This was a retrospective chart review of adult inpatients with MSSA bacteremia during the pre-PCR (Jun 2018 - Dec 2019) and post-PCR (Jun 2020 - Dec 2021) study periods. Patients were excluded if they did not have PCR testing performed (post-PCR group only), never achieved optimal antibiotic therapy, had a polymicrobial infection, had positive blood cultures in the prior 90 days, underwent penicillin-skin testing or β-lactam desensitization, or were transitioned to comfort care or deceased within 24 hours of the gram stain. The primary endpoint was the difference in time to starting optimal MSSA antibiotic therapy (oxacillin or cefazolin) between the pre-PCR and post-PCR groups. Secondary endpoints included duration of anti-MRSA antibiotic use, in-hospital mortality, hospital and ICU lengths of stay, duration of bacteremia, and 30-day MSSA-related and all-cause readmissions. Results A total of 200 patients were included in the study, with 100 patients in each group. Time to optimal therapy was reduced by 19.9 hours in the post-PCR group (p &amp;lt; 0.001). Fewer patients in the post-PCR group were initiated on empiric anti-MRSA antibiotic therapy than in the pre-PCR group (84% vs 98%, respectively, p = 0.001). PCR implementation was also associated with shorter empiric anti-MRSA antibiotic use and duration of bacteremia. There were no significant differences in length of stay, in-hospital mortality, or 30-day MSSA-related or all-cause readmissions (Table 1). Table 1: Primary and Secondary Endpoints Conclusion In patients with MSSA bacteremia, BCID PCR panel testing decreased time to optimal MSSA antibiotic therapy and reduced durations of bacteremia and empiric anti-MRSA antibiotic therapy, including vancomycin. Disclosures All Authors: No reported disclosures

155. Use of MRSA PCR and Antimicrobial Stewardship Intervention to Limit Anti-MRSA Therapy in Respiratory Tract Infections at a Community Teaching Hospital

Abstract Background Patients admitted to the hospital with respiratory tract infections (RTIs) who are at risk for MRSA are often treated empirically with anti-MRSA agents such as vancomycin or linezolid. While pre-treatment respiratory culture is recommended, it is not always feasible. An alternate, more easily obtainable test is the MRSA nasal PCR, which is used to detect nasal colonization. While a positive nasal MRSA PCR cannot determine MRSA pneumonia, a negative MRSA PCR result strongly correlates with lack of MRSA pneumonia providing a useful antimicrobial stewardship tool for de-escalation or avoidance of empiric anti-MRSA therapy. Our Antimicrobial Stewardship Program (ASP) routinely follows patients admitted with RTIs and provides recommendations for appropriate therapy based on culture and test results, including the MRSA PCR. The purpose of our quality improvement project was to assess the practice and clinical impact of reduction of specific MRSA therapy associated with a negative nasal MRSA PCR. Methods We performed a retrospective review of patients admitted to our institution with MRSA PCRs performed for the purpose of RTI workup from November-December 2022. We compared patients with negative MRSA PCRs (not detected or MSSA) with and without ASP intervention and assessed differences in patient characteristics and outcomes. If ASP intervention occurred, intervention and acceptance data was collected. Characteristics were compared using descriptive statistics. Results Shown in Table 1 and 2. There was no significant difference in age, sex, duration of MRSA therapy, SCr, length of stay, or readmission between groups. When looking at ASP intervention for 1. discontinuation of MRSA therapy or 2. ordering/collecting MRSA PCR, a total of 73 interventions occurred with a 100% acceptance rate. This encompassed 34% (52/155) of patients on MRSA therapy with a negative PCR result. Conclusion While no significant difference was found between groups in terms of duration of MRSA therapy, the slightly shorter duration in the non-ASP group was likely due to prior discontinuation of MRSA therapy thus not necessitating ASP intervention. Those with slightly longer duration received ASP intervention which led to discontinuation of unnecessary MRSA therapy. Disclosures Thomas M. File, Jr., MD, MSc, MACP, FIDSA, HealthTrackRx: Advisor/Consultant|NAbriva Therapeutics: Advisor/Consultant|ThermoFisher Scientific: Advisor/Consultant

1266. Refining Antimicrobial Stewardship by De-escalating Vancomycin Using MRSA (Methicillin Resistant Staphylococcus aureus) Nasal Screening in a Community Hospital Setting

Abstract Background Our institution has prioritized appropriate use of anti-Methicillin-resistant Staphylococcus aureus (MRSA) drugs such as vancomycin. The overuse of anti-MRSA drugs contributes to drug toxicities and development of resistant organisms such as vancomycin-resistant enterococcus (VRE). Recent studies show that MRSA nasal surveillance screening has a high negative predictive value of 96.5% in all types of pneumonia. At our community hospital a decentralized pharmacist-driven MRSA nares screening protocol was novel. We report the results of implementing a MRSA nares screening protocol for vancomycin de-escalation in pneumonia patients. Methods A decentralized pharmacist reviewed patients with a diagnosis of pneumonia and prescribed vancomycin. The pharmacist ensured that a culture-based MRSA nares screen was performed within 48 hours of admission, if not already ordered. If the nares screen returned negative and respiratory cultures did not grow MRSA at 48 hours, the decentralized pharmacist contacted the medical team to recommend discontinuing vancomycin. Reasons for exclusion included a positive respiratory culture for MRSA within the prior 7 days, septic shock, alternative site of MRSA infection, and greater than 48 hours of anti-MRSA therapy at time of swab collection. Results 164 patients were reviewed by pharmacy between 6/16/22 and 4/25/23. 98% of MRSA nares screening had been performed within 48 hours of admission. MRSA screen was ordered by the decentralized pharmacist in 44% of patients. 89% of patients screened were negative for MRSA and reviewed for de-escalation of vancomycin. In 40% of patients, vancomycin was discontinued after recommendations by the decentralized pharmacist, with 95% of the recommendations accepted by the primary hospitalist physician. 37% of patients' vancomycin was discontinued by the attending physician. Overall, 77% of patients with negative MRSA nasal screen results were successfully de-escalated. Conclusion Our data highlights the effectiveness of close physician-pharmacy collaboration. Most nares cultures were negative for MRSA allowing for de-escalation of antibiotics. Pharmacist recommendations were accepted majority of the time. Given the data, we plan to apply this approach for other ongoing stewardship initiatives. Disclosures All Authors: No reported disclosures

2573. The Use of MRSA PCR for De-escalation of Anti-MRSA therapy for CAP and HAP at a Community Hospital: a Quality Improvement Analysis for Antibiotic Stewardship

Abstract Background The use of nasal MRSA PCR is beneficial in reducing the duration of anti-MRSA therapy, since it can rapidly be attained and has excellent negative predictive value. There is scarcity of literature regarding the potential impact of MRSA PCR on the length of stay and cost of care at a community hospital, when considering empiric treatment of CAP or HAP. Methods This retrospective analysis was conducted at Naples Community Hospital, a 588-bed facility. We assessed 134 patients that were admitted for treatment of pneumonia who received anti-MRSA therapy for CAP or HAP from March to April 2023. Our approach was to employ a pharmacy-driven protocol whereby adult patients who had received either vancomycin, linezolid, or both during their hospitalization were screened with MRSA nares PCR shortly after initiation of anti-MRSA therapy. The primary outcome was the duration of anti-MRSA treatment in hours. Secondary outcomes assessed included time from MRSA colonization status result to the discontinuation of anti-MRSA therapy, with subgroup analyses of the percentage of patients with vancomycin trough levels drawn in the vancomycin group, the incidence of acute kidney injury and hospital length of stay pre- and post-implementation. Results Our analysis showed a primary outcome with a statistically significant reduction in the hours of anti-MRSA therapy duration when comparing pre- and post-implementation of MRSA PCR (64 vs. 40 hours, P= 0.0008). A considerable improvement was noted in the total duration of anti-MRSA therapy (26 vs. 11 hours, P=0.0006). Our study showed a reduced in length of stay; however, was not statistically significant between the two groups (206 vs 142 hours, P=0.066). No statistical difference was noted in the incidence of AKI between groups. Conclusion Our study suggests that pharmacy-driven protocols employed in community hospitals can significantly aid in reduction of inappropriate use of anti-MRSA empiric therapy and reduce costs associated with unnecessary antibiotics. Our analysis showed a trend to shorter length of stay post-implementation, which shortened duration of anti-MRSA therapy. Further investigation with a larger sample size, may also show a significant reduction in length of stay. Disclosures All Authors: No reported disclosures

Impact of Limiting Vancomycin Loading Doses in Patients With Methicillin-resistant Staphylococcus aureus Infections After Hospital Protocol Revision.

Background: Vancomycin loading doses are commonly used to quickly attain target serum concentrations; however, data supporting their effect on clinical patient outcomes is limited. In April 2020, our institution revised our pharmacist-driven vancomycin dosing protocol to reserve loading doses for hemodynamically unstable patients with suspected serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Prior to the protocol update, all patients treated with vancomycin at our institution received a weight-based loading dose. The purpose of this study is to assess clinical efficacy and safety outcomes related to the use of vancomycin loading doses. Methods: A retrospective, quasi-experimental study was performed to compare clinical outcomes in adult patients treated with vancomycin for laboratory-confirmed MRSA infections. Patients who received vancomycin therapy prior to our institution's vancomycin dosing protocol revisions (pre-intervention) were compared to patients who received vancomycin after the revisions (post-intervention). The primary outcome was all-cause, inpatient mortality. Secondary outcomes included persistent signs and symptoms of infection ≥5 days after vancomycin initiation, switch to alternative anti-MRSA therapy, and nephrotoxicity. Results: A total of 122 patients (63 pre-intervention patients and 59 post-intervention patients) were included. Receipt of a vancomycin loading dose did not impact the rate of inpatient mortality (4.76%vs 6.78%; OR 1.46, 95% CI [0.31, 6.79]). All secondary outcomes were similar between the two groups, including persistent signs and symptoms of infection, switch to alternative anti-MRSA therapy, and nephrotoxicity. Conclusions: Routine use of vancomycin loading doses is not associated with improved outcomes in hemodynamically stable patients with MRSA infections.

Evaluation of the Effectiveness and Use of Anti-Methicillin-Resistant Staphylococcus aureus Agents for Aspiration Pneumonia in Older Patients Using a Nationwide Japanese Administrative Database.

Studies indicated potential harm from empirical broad-spectrum therapy. A recent study of hospitalizations for community-acquired pneumonia suggested that empirical anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy was associated with an increased risk of death and other complications. However, limited evidence supports empirical anti-MRSA therapy for older patients with aspiration pneumonia. In a nationwide Japanese database, patients aged ≥65 years on admission with aspiration pneumonia were analyzed. Patients were divided based on presence of respiratory failure and further sub-categorized based on their condition within 3 days of hospital admission, either receiving a combination of anti-MRSA agents and other antibiotics, or not using MRSA agents. An inverse probability weighting method with estimated propensity scores was used. Out of 81,306 eligible patients, 55,098 had respiratory failure, and 26,208 did not. In the group with and without respiratory failure, 0.93% and 0.42% of the patients, respectively, received anti-MRSA agents. In patients with respiratory failure, in-hospital mortality (31.38% vs. 19.03%, p < 0.001), 30-day mortality, and 90-day mortality were significantly higher, and oxygen administration length was significantly longer in the anti-MRSA agent combination group. Anti-MRSA agent combination use did not improve the outcomes in older patients with aspiration pneumonia and respiratory failure, and should be carefully and comprehensively considered.

Fear of missing organisms (FOMO): Diabetic foot and osteomyelitis management opportunities

Background: Hospitalizations for diabetic foot infections and lower-extremity osteomyelitis are common. Use of empiric antibiotic therapy for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa is also common. Guidelines recommend antibiotic therapy based on severity of illness, risk factors for MRSA and P. aeruginosa, and local prevalence. We evaluated the concordance between empiric antibiotic therapy and both culture results and definitive antibiotic therapy with a focus on MRSA and P. aeruginosa. We also evaluated how well MRSA and pseudomonal risk factors were predictive of culture results with these organisms. Methods: We conducted a cohort study of all patients admitted to our hospital system in 2021 with a diagnosis of a diabetic foot infection or lower-extremity osteomyelitis. Patients were included if they had an International Classification of Disease, Tenth Revision (ICD-10) diagnosis code of M86, E10.621, E11.621, or E08.621. Patients were excluded if antibiotics were for another indication or if they were aged &lt;18 years. In patients with multiple hospitalizations only the first hospitalization was included. Empiric antibiotic therapy included antibiotics started by the admitting team. Definitive antibiotic therapy included the final antibiotic course either completed during admission or prescribed at the time of discharge. MRSA risk factors included prior positive culture with MRSA within the last year, hospitalization with IV antibiotics within 90 days, intravenous drug use, or hemodialysis. Pseudomonal risk factors included prior positive culture with P. aeruginosa within the last year or hospitalization with IV antibiotics within 90 days. Results: In 2021, 260 unique patients were admitted with suspected diabetic foot infections or lower-extremity osteomyelitis. 68 patients had &gt;1 admission. Empiric anti-MRSA and antipseudomonal therapy was administered to 224 (86%) and 214 (82%) patients, respectively. Definitive anti-MRSA and antipseudomonal therapy was administered to 76 (30%) and 51 (20%) patients, respectively. Of the 195 patients who had wound cultures, 29 (15%) and 18 (9%) had positive cultures for MRSA and P. aeruginosa respectively (Fig.). The negative predictive value of MRSA risk factors for predicting a negative culture with MRSA was 91%. The negative predictive value of pseudomonal risk factors for predicting a negative culture with P. aeruginosa was 95%. Conclusions: Our data suggest an opportunity for substantial reductions in empiric anti-MRSA and antipseudomonal therapy for diabetic foot infection and lower-extremity osteomyelitis. The absence of MRSA and pseudomonal risk factors was reasonably good at predicting the absence of a positive culture with these organisms.Disclosure: None

Impact of the FilmArray Rapid Multiplex PCR Assay on Clinical Outcomes of Patients with Bacteremia.

Bacteremia is a serious disease with a reported mortality of 30%. Appropriate antibiotic use with a prompt blood culture can improve patient survival. However, when bacterial identification tests based on conventional biochemical properties are used, it takes 2 to 3 days from positive blood culture conversion to reporting the results, which makes early intervention difficult. Recently, FilmArray (FA) multiplex PCR panel for blood culture identification was introduced to the clinical setting. In this study, we investigated the clinical impact of the FA system on decision making for treating septic diseases and its association with patients' survival. Our hospital introduced the FA multiplex PCR panel in July 2018. In this study, blood-culture-positive cases submitted between January and October 2018 were unbiasedly included, and clinical outcomes before and after the introduction of FA were compared. The outcomes included (i) the duration of use of broad-spectrum antibiotics, (ii) the time until the start of anti-MRSA therapy to MRSA bacteremia, and (iii) sixty-day overall survival. In addition, multivariate analysis was used to identify prognostic factors. In the FA group, overall, 122 (87.8%) microorganisms were concordantly retrieved with the FA identification panel. The duration of ABPC/SBT use and the start-up time of anti-MRSA therapy to MRSA bacteremia were significantly shorter in the FA group. Sixty-day overall survival was significantly improved by utilizing FA compared with the control group. In addition, multivariate analysis identified Pitt score, Charlson score, and utilization of FA as prognostic factors. In conclusion, FA can lead to the prompt bacterial identification of bacteremia and its effective treatment, thus significantly improving survival in patients with bacteremia.