anti-MRSA Therapy Research Articles

Evaluation of Anti-Methicillin-Resistant Staphylococcus aureus (MRSA) Prescribing Habits in Patients with a Positive MRSA Nasal Swab in the Absence of Positive Cultures.

Methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nasal swabs are guideline-recommended de-escalation tools in certain patients with pneumonia. Prior studies have demonstrated reduced anti-MRSA therapy with negative results, but the impact on durations of therapy has been poorly elucidated in patients with positive PCRs. The objective of this review was to evaluate anti-MRSA treatment durations in patients with a positive MRSA PCR in the absence of MRSA growth on culture. This was a single-center, retrospective observational study evaluating 52 hospitalized, adult patients receiving anti-MRSA therapy with positive MRSA PCRs. The overall median duration of anti-MRSA therapy was five days, including a median of four days after PCR results. This was consistent among intensive care unit (ICU) and non-ICU patient populations and in patients with suspected community-acquired pneumonia (CAP). Among patients with hospital-acquired pneumonia (HAP), the median duration of anti-MRSA therapy was seven days, with a median of six days after PCR results. Overall, patients received a median duration of anti-MRSA therapy that would constitute a full treatment course for many respiratory infections, which indicates that providers may equate a positive MRSA nasal PCR with positive culture growth and highlights the need for education on the interpretation of positive tests.

Photothermal and natural activity-based synergistic antibacterial effects of Ti3C2Tx MXene-loaded chitosan hydrogel against methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) has strong resistance to antibiotic therapy. In this regard, developing antibiotic-free antibacterial agents is of great significance to treat MRSA infections. Herein, we loaded Ti3C2Tx MXene nanomaterial in the non-crosslinked chitosan (CS) hydrogel. The obtained MX-CS hydrogel is expected to not only adsorb MRSA cells via CS-MRSA interactions, but also gather the MXene-induced photothermal hyperthermia, achieving the efficient and intensive anti-MRSA photothermal therapy. As a result, under NIR irradiation (808 nm, 1.6 W/cm2, 5 min), MX-CS showed a greater photothermal effect than MXene alone did (30 μg/mL, 49.9 °C for MX-CS and 46.5 °C for MXene). Importantly, MRSA cells were rapidly adsorbed on MX-CS hydrogel (containing 30 μg/mL MXene) and completely inhibited (99.18 %) under NIR irradiation for 5 min. In contrast, MXene (30 μg/mL) and CS hydrogel alone only inhibited 64.52 % and 23.72 % MRSA, respectively, significantly lower than the inhibition caused by MX-CS (P < 0.001). Interestingly, when the hyperthermia was depleted by a 37 °C water bath, the bacterial inhibition rate of MX-CS significantly decreased to 24.65 %. In conclusion, MX-CS hydrogel has a remarkable synergistic anti-MRSA activity by gathering MRSA cells and MXene-induced hyperthermia, and may have great potentials in treating MRSA-infected diseases.

Estimated mortality with early empirical antibiotic coverage of methicillin-resistant Staphylococcus aureus in hospitalized patients with bacterial infections: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis to estimate the effect of early active empirical antibiotics for MRSA on mortality, both in patients admitted with MRSA infections and in patients admitted with common infectious syndromes, for whom the causative pathogen may not have been MRSA. A systematic literature search was conducted using Embase, MEDLINE, PubMed, Web of Science, Cochrane, Scopus and Google Scholar from the earliest entry through to 26 April 2022. We included studies of patients hospitalized with culture-proven MRSA infections that compared mortality rates depending on whether patients received active empirical antibiotics. The primary outcome was the adjusted OR for mortality with early active empirical antibiotics. After performing random-effects meta-analysis, we estimated the absolute risk reduction in mortality with initial empirical MRSA coverage for common infectious syndromes based on the prevalence of MRSA and baseline mortality rate for each syndrome, as reported in the medical literature. Of an initial 2136 unique manuscripts, 37 studies (11 661 participants) met our inclusion criteria. Fifteen studies (6066 participants) reported adjusted OR of mortality. The pooled adjusted OR for mortality was 0.64 (95% CI, 0.48-0.84), favouring active empirical antibiotics. The estimated absolute mortality benefit was 0% for patients with pneumonia, 0.1% (95% CI, 0.04-0.2) for non-critically ill patients with soft tissue infections, 0.04% (95% CI, 0.01-0.05) for non-critically ill patients with urinary tract infections, 0.6% (95% CI, 0.2-1.0) for patients with septic shock, and 1.0% (95% CI, 0.3-1.4) for patients with catheter-related infections admitted to ICUs. For the three most common infections in the hospital, the absolute benefit on mortality of empirical antibiotics against MRSA is 0.1% or less. Meaningful benefit of empirical antimicrobials against MRSA is limited to patients with approximately 30% mortality and 10% prevalence of MRSA. Avoiding empirical antibiotics against MRSA for low-risk infections would substantially reduce the use of anti-MRSA therapy.

Development and Evaluation of Novel Encapsulated Isoeugenol-Liposomal Gel Carrier System for Methicillin-Resistant Staphylococcus aureus.

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) bacteria have seriously threatened the health and safety of the world's population. This challenge demands the development of alternative therapies based on plant origin. This molecular docking study ascertained the orientation and intermolecular interactions of isoeugenol within penicillin-binding protein 2a. In this present work, isoeugenol as an anti-MRSA therapy was selected by encapsulating it into a liposomal carrier system. After encapsulation into the liposomal carrier, it was evaluated for encapsulation efficiency (%), particle size, zeta potential, and morphology. The percentage entrapment efficiency (% EE) was observed to be 57.8 ± 2.89% with a particle size of 143.31 ± 7.165 nm, a zeta potential of (-)25 mV, and morphology was found to be spherical and smooth. After this evaluation, it was incorporated into a 0.5% Carbopol gel for a smooth and uniform distribution on the skin. Notably, the isoeugenol-liposomal gel was smooth on the surface with a pH of 6.4, suitable viscosity, and spreadability. Interestingly, the developed isoeugenol-liposomal gel was safe for human use, with more than 80% cell viability. The in vitro drug release study shows promising results with 75.95 ± 3.79% of drug release after 24 h. The minimum inhibitory concentration (MIC) was 8.236 µg/mL. Based on this, it can be concluded that encapsulating isoeugenol into the liposomal gel is a potential carrier for MRSA treatment.

Multifaceted Evaluation of Antibiotic Therapy as a Factor Associated with Candidemia in Non-Neutropenic Patients.

We aimed to evaluate various aspects of antibiotic therapy as factors associated with candidemia in non-neutropenic patients. A retrospective, matched, case-control study was conducted in two teaching hospitals. Patients with candidemia (cases) were compared to patients without candidemia (controls), matched by age, intensive care unit admission, duration of hospitalization, and type of surgery. Logistic regression analyses were performed to identify factors associated with candidemia. A total of 246 patients were included in the study. Of 123 candidemia patients, 36% had catheter-related bloodstream infections (CRBSIs). Independent factors in the whole population included immunosuppression (adjusted odds ratio [aOR] = 2.195; p = 0.036), total parenteral nutrition (aOR = 3.642; p < 0.001), and anti-methicillin-resistant S. aureus (MRSA) therapy for ≥11 days (aOR = 5.151; p = 0.004). The antibiotic factor in the non-CRBSI population was anti-pseudomonal beta-lactam treatment duration of ≥3 days (aOR = 5.260; p = 0.008). The antibiotic factors in the CRBSI population included anti-MRSA therapy for ≥11 days (aOR = 10.031; p = 0.019). Antimicrobial stewardship that reduces exposure to these antibacterial spectra could help prevent the development of candidemia.

Antibiotic de-escalation in pneumonia with pharmacist education and ordering of methicillin-resistant Staphylococcus aureus nasal swabs

IntroductionWhen methicillin-resistant Staphylococcus aureus (MRSA) is the causative pathogen in pneumonia, in-hospital mortality rate is approximately 31.2%. However, the occurrence of MRSA pneumonia is uncommon, with a reported incidence of...

Implementation of MRSA Nasal Swabs as an Antimicrobial Stewardship Intervention to Decrease Anti-MRSA Therapy in COVID-19 Infection.

In the early stages of treating patients with SARS-CoV-2, limited information was available to guide antimicrobial stewardship interventions. The COVID-19 Task Force and Antimicrobial Stewardship Committee, at a 988-bed academic medical center, implemented the use of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab polymerase chain reaction (PCR) testing to assist with the de-escalation of anti-MRSA therapy in patients with suspected superimposed bacterial pneumonia in COVID-19. A retrospective study was conducted to evaluate the impact of MRSA nasal swab PCR testing on the rate of anti-MRSA therapy between 13 April 2020 and 26 July 2020. A total of 122 patients were included in the analysis. Of the patients included in the final analysis, 58 (47.5%) had anti-MRSA therapy discontinued and 41 (33.6%) avoided anti-MRSA therapy completely due to a negative swab result. With the implementation of MRSA nasal swab PCR testing in COVID-19 patients, anti-MRSA therapy was reduced in 81% of patients in this study. In patients who continued with anti-MRSA therapy, nasal swabs were either positive for MRSA or an alternative indication for anti-MRSA therapy was noted. Only three patients in the cohort had MRSA identified in a sputum culture, all of whom had anti-MRSA therapy continued. MRSA nasal swab PCR testing may serve as an effective antimicrobial stewardship tool in COVID-19 pneumonia.

Positivity of repeat nasal MRSA PCR screening: a single-center experience.

Repeating nasal methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reactions (PCRs) within 14 days may increase healthcare costs and inform anti-MRSA antibiotic therapy without known benefit. Within an inpatient admission, our retrospective, single-center evaluation found that conversion from negative to positive on repeat nasal MRSA PCR screen was uncommon (2%).

2172. Closing the CAP Gap: Improving the Management of Community Acquired Pneumonia (CAP)

Abstract Background In October 2019 updated community acquired pneumonia (CAP) guidelines were published, highlighting indications for empiric anti-MRSA and antipseudomonal antibiotics and use of MRSA nares screens. During a review of patients receiving vancomycin and piperacillin-tazobactam at our institution in 2020 we noted frequent use of anti-MRSA and antipseudomonal antibiotics and infrequent use of MRSA nares screens for CAP. In May 2020 we initiated a multifaceted intervention, including prospective audit and feedback, an updated pneumonia order set, and system-wide education. In this study we sought to describe gaps in the care of patients with CAP at our institution and to evaluate the impact of a multifaceted intervention on those gaps in care. Methods We performed a retrospective cohort study on a random sample of unique adult patients admitted with pneumonia from January 1, 2020 through June 30, 2021. Exclusion criteria included COVID infection within 4 weeks of admission, no antibiotics for pneumonia given during admission, immunocompromised condition, and diagnosis of hospital-acquired or ventilator-associated pneumonia. The primary objective was to describe the percentage of patients receiving appropriate anti-MRSA and antipseudomonal therapy and MRSA nares testing during the study period. The secondary objective was to compare appropriateness of these outcomes before and after the intervention. Study groups Results For the 126 patients reviewed, 68.3% received the appropriate empiric spectrum of activity for MRSA and Pseudomonas aeruginosa, improving from 60% to 80% before and after the intervention respectively. The percentage of patients screened for MRSA increased from 6 to 34%; however, the percentage of appropriate MRSA screens decreased from 71 to 54% because screens were often collected despite absence of MRSA risk factors. Results Conclusion The percentage of patients receiving appropriate anti-MRSA and antipseudomonal therapy for CAP improved after a multifaceted stewardship intervention. The percentage of patients for whom appropriate MRSA nares screens was performed worsened, mainly due to use of MRSA nares screens when not needed. Disclosures All Authors: No reported disclosures.

1834. Evaluation of De-Escalation Options after Combination Daptomycin and Ceftaroline Therapy for Persistent MRSA Bacteremia

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia carries high mortality with limited treatment options. Studies over the last decade support glycolipopeptide and beta-lactam combination therapy with daptomycin (DAP) and ceftaroline (CFT) combination gaining prominence. While data supports de-escalation to monotherapy after bacteremia clearance it does not guide the choice of agent. With barriers including accessibility, cost, and tolerability of these agents, data is needed to optimize treatment. This study aims to evaluate de-escalation options after combination DAP/CFT therapy for persistent MRSA bacteremia. Methods A single-center, retrospective review of cases of persistent MRSA bacteremia (defined as greater than 72 hours on appropriate therapy) requiring escalation to DAP/CFT between 2014 and 2021 was performed. Details of bacteremia, source of infection, and comorbidities were assessed, and outcomes including recurrence of infection, infection-associated mortality, and tolerability were compared using exact Chi-square testing and univariant analysis. Results Sixty-six cases were identified of which 7 were de-escalated to vancomycin (VAN), 48 to DAP, 4 to CFT, and 7 continued DAP/CFT combination. Demographics and details of bacteremia such as prior anti-MRSA therapy, duration prior to DAP/CFT therapy, and source identification were similar between groups. Differences included higher rates of hemodialysis patients in the VAN group, higher rates of immunocompromised hosts in the DAP group, higher average Pitt bacteremia score in the DAP/CFT group, and lower rates of source control in the VAN group. Recurrence of infection (29% VAN, 13% DAP, 25% CFT) and infection-related mortality (14% VAN, 8% DAP) were higher in the VAN group (p=0.0452). In the DAP group 23% required change in therapy during their course. Univariant analysis assessing for confounding from comorbidities and source control yielded no significant associations. Conclusion This study is limited by small, uneven sample sizes but the results identify a trend of increased recurrence rates and mortality with de-escalation to VAN but tolerability concerns with DAP. More study is needed to guide clinical care and this data provides framework for future research. Disclosures All Authors: No reported disclosures.

900. Evaluation of automated blood culture results and subsequent pharmacist intervention on time to targeted therapy in patients with bacteremia

Abstract Background Bloodstream infections (BSIs) are associated with a high mortality rate and timely administration of empiric broad-spectrum antibiotics is critical. However, prolonged exposure increases the risk of colonization and subsequent infection with resistant bacteria. The use of rapid diagnostics and prospective audit and feedback allows for decreased time to targeted therapy and development of resistance. Methods This quasi-experimental study aimed to evaluate changes in time to targeted antibiotic therapy before and after implementation of a real-time pharmacist notification for bacteremic patients. The pre- and post- intervention periods were 9/1/19–12/31/19 and 9/1/21– 12/31/21, respectively. Bacteremic patients that were identified via automated Bruker’s MBT Sepsityper IVD kit reports and admitted for ≥48 hours were included in the study. Patients were excluded if they had ≥ 1 BSI or polymicrobial BSI during hospitalization, treatment of a concurrent infection, or transitioned to hospice. The primary outcome was change in time to targeted antibiotic therapy. Secondary outcomes included change in broad-spectrum antibiotic days of therapy, total duration therapy, hospital length of stay, and in-hospital all-cause mortality. Results A total of 132 charts were reviewed, 83 of which were included, with 47 in the pre- and 36 in the post-intervention group. The most common isolates in the study across both groups was E. coli (36.1%), Klebsiella spp. (15.7%), MSSA (15.7%) and MRSA (8.4%). A trend towards decreased time to targeted therapy was seen in the post-intervention group (5.4 hours vs 33.0 hours; p = 0.150). Median duration of anti-MRSA therapy was reduced from 49.4 hours in the pre-intervention group to 27.92 hours in the post-intervention group (p=0.035). There was no significant difference in total duration of therapy, days of anti-pseudomonal therapy, length of stay, or in-hospital all-cause mortality. Of the 22 pharmacist interventions, 18 (81.8%) were accepted. The most common pharmacist intervention was therapy de-escalation (72.7%). Conclusion Automated rapid blood culture diagnostic results used in conjunction with real-time notifications to pharmacists, further decreased time to targeted therapy and significantly reduced duration of anti-MRSA therapy. Disclosures All Authors: No reported disclosures.

MRSA and Skin Infections in Psoriatic Patients: Therapeutic Options and New Perspectives.

Psoriatic patients present various infectious risk factors, but there are few studies in the literature evaluating the actual impact of psoriasis in severe staphylococcal skin infections. Our narrative review of the literature suggests that psoriatic patients are at increased risk of both colonization and severe infection, during hospitalization, by S. aureus. The latter also appears to play a role in the pathogenesis of psoriasis through the production of exotoxins. Hospitalized psoriatic patients are also at increased risk of MRSA skin infections. For this reason, new molecules are needed that could both overcome bacterial resistance and inhibit exotoxin production. In our opinion, in the near future, topical quorum sensing inhibitors in combination with current anti-MRSA therapies will be able to overcome the increasing resistance and block exotoxin production. Supplementation with Vitamin E (VE) or derivatives could also enhance the effect of anti-MRSA antibiotics, considering that psoriatic patients with metabolic comorbidities show a low intake of VE and low serum levels, making VE supplementation an interesting new perspective.

Pharmacist-Driven Methicillin-Resistant S. aureus Polymerase Chain Reaction Testing for Pneumonia.

Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) can be detected using nasal swab polymerase chain reaction (PCR) assay and is associated with clinical MRSA infection. The MRSA nasal PCR has a rapid turnaround time and a negative predictive value for MRSA pneumonia of >98%; however, data are limited in critically ill patients. The purpose of this study is to determine the impact of a pharmacist-driven algorithm, utilizing MRSA PCR nasal screening on duration of anti-MRSA therapy in patients admitted to the intensive care unit (ICU) with suspected pneumonia. A single-center pre/post study was conducted in 4 ICUs at a large tertiary care community hospital. Adult patients admitted to the ICU initiated on vancomycin or linezolid for pneumonia managed using a pharmacist-driven MRSA PCR algorithm were included in the algorithm cohort. A historical cohort with standard management was matched 1:1 by age, type of pneumonia, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The primary outcome was duration of anti-MRSA therapy. Secondary outcomes included MRSA rates, number of vancomycin levels, new onset of acute kidney injury (AKI), ICU length of stay (LOS), hospital LOS, and mortality. Of the 245 patients screened, 50 patients met inclusion criteria for the algorithm cohort and were matched to 50 patients in the historical cohort. The duration of anti-MRSA therapy was significantly lower compared with the historical cohort (47 vs 95 hours; P < 0.001). Secondary outcomes were similar between groups for MRSA rates, new onset of AKI, LOS, and mortality. There were less vancomycin levels ordered in the algorithm cohort (2 vs 3, P = 0.026). A pharmacist-driven MRSA PCR algorithm significantly reduced anti-MRSA duration of therapy in critically ill patients with pneumonia. Future studies should validate these results in critically ill populations and in settings where MRSA pneumonia is more prevalent.

Duration of Gram-negative antibiotic therapy in patients with pneumonia prior to and after the implementation of MRSA nasal swabs, an antimicrobial stewardship tool.

The implementation of MRSA PCR nasal swabs has been shown to decrease the use of anti-MRSA therapies through faster antibiotic de-escalation in patients with pneumonia. While this benefit has been shown exclusively in Gram-positive therapy, swab results may lead to additional antibiotic de-escalation discussions early on, potentially providing reduced durations or de-escalations of Gram-negative therapy as well. To determine if early de-escalation discussions prompted by MRSA swab results lead to shorter durations of Gram-negative antibiotic therapy. A retrospective chart review was conducted to compare pneumonia duration of Gram-negative therapy pre- and post-implementation of MRSA nasal swabs. Time to de-escalation, time to conversion to enteral therapy and cost were also compared between the groups. Data were collected for 240 patients overall, 120 in each group. The median duration of Gram-negative therapy was 154.0 h in the post-implementation group and 176.4 h in the pre-implementation group (P = 0.002). There was no significant difference in time to de-escalation (52.7 versus 54.9 h; P = 0.351) or time to transition from IV to enteral therapy (53.0 versus 57.3 h; P = 0.289). The median cost of Gram-negative regimens per patient was less expensive in the post-implementation group ($31.36 versus $45.90; P = 0.002). MRSA nasal swabs as an antimicrobial stewardship tool were associated with a reduced overall duration of Gram-negative therapy and Gram-negative antibiotic regimen cost. This introduces an additional benefit of MRSA nasal swabs and further incentivizes their use as an antimicrobial stewardship tool.

Urea-Based Ligand as an Efflux Pump Inhibitor: Warhead to Counter Ciprofloxacin Resistance and Inhibit Collagen Adhesion by MRSA

Methicillin-resistant Staphylococcus aureus (MRSA) is a frontline human pathogen in which efflux pump activity confers high levels of antibiotic-resistance and poses a therapeutic challenge in the clinics. The present study illustrates the potential of urea-based ligand as an efflux pump inhibitor (EPI) in order to restore the efficacy of ciprofloxacin (CPX) against MRSA. Among eight structurally varying urea-based ligands, the ligand C8 could significantly inhibit efflux pump activity in the clinical MRSA strain S. aureus 4s and was superior to the known EPI reserpine. In combinatorial treatment, C8 enhanced cellular accumulation of CPX, rendered a 16× decrease in the MIC of CPX, and restored the susceptibility of S. aureus 4s to CPX. Notably, C8 downregulated the expression of norA gene coding for the efflux pump in MRSA and treatment with 10 μM C8 and 2.0 μM CPX prevented emergence of the CPX resistance trait and suppressed MRSA cell growth till 120 generations. For potential anti-MRSA therapy, C8-loaded poly(d,l-lactide-co-glycolide) nanocarrier (C8-PNC) was generated, which facilitated facile release of C8 in physiologically relevant fluid. C8-PNC (loaded with 50 μM C8) rendered efflux pump inhibition and eliminated MRSA in combination with only 2.0 μM CPX. Treatment with the non-toxic C8-PNC (loaded with 50 μM C8) and CPX (2.0 μM) also hindered MRSA adhesion on collagen manifold higher as compared to cells treated with 32 μM CPX and significantly downregulated norA gene expression in non-adhered MRSA cells. The urea-based ligand presented herein is a promising biocompatible therapeutic material for effective mitigation of MRSA infections.

Superoxide Radical-Mediated Self-Synthesized Au/MoO3-x Hybrids with Enhanced Peroxidase-like Activity and Photothermal Effect for Anti-MRSA Therapy.

A rapid increase in methicillin-resistant Staphylococcus aureus (MRSA) induced infection has been noticed in recent years and the biofilm formed by MRSA further delays wound healing, causing a high mortality rate. Hence, a safe and effective superoxide radical (O2•-) mediated self-synthesis strategy is developed to prepare Au-doped MoO3-x (Au/MoO3-x) plasmonic-semiconductor hybrid for the elimination of MRSA mediated wound infection. The synthesis mechanism of Au NPs is systematically investigated, proving that O2•- plays a key role in reduction of HAuCl4 into Au NPs in the presence of H2O and O2. Au-doped MoO3-x exhibits the improved photothermal conversion efficiency (∼52.40%) compared with MoO3-x (∼41.11%). Moreover, the peroxidase (POD)-like activity of Au/MoO3-x hybrid is higher than that of MoO3-x NPs, resulting in increased yield of highly toxic ·OH. In combination with the enhanced photothermal and POD-like properties, Au/MoO3-x hybrid achieves efficient elimination of MRSA bacteria with eradication ratio of ∼99.76%. Additionally, the as-prepared Au/MoO3-x NPs exhibit excellent biosafety, which is verified via in vitro and in vivo experiments. This study provides the basis for exploring MoO3-x-based hybrids via a green O2•--mediated self-synthesis approach.

1138. Utility of Methicillin-resistant Staphylococcus aureus Nares Screening in Hospitalized Children With Acute Infectious Disease Syndromes

BackgroundEmpirical antibiotic regimens frequently include treatment for methicillin-resistant Staphylococcus aureus (MRSA). Studies in adults with pneumonia support the use of a negative MRSA nares screening (MNS) to help de-escalate antibiotic therapy. Comparable pediatric data in the literature is scarce. We aimed to evaluate the use of MNS for antibiotic de-escalation in hospitalized children (< 18 years) at a tertiary children’s hospital. MethodsA retrospective chart review was conducted of pediatric inpatients (January 01, 2015 to December 31, 2020) with a presumed infectious diagnosis who had a PCR-based MNS test and a clinical culture (i.e. site of infection or blood) performed as part of their diagnostic work up. Those who were screened >5 days since admission or > 48 hours since start of MRSA-active antimicrobials, and those who had antibiotic treatment withdrawn after 48 hours because of negative cultures were excluded. ResultsA total of 101 children were included with a median age (range) of 2 years (0-17) and about half (n=57, 56.4%) were male. Top three diagnosis groups were skin and soft tissue infections (n=33, 32.7%), toxin-mediated syndromes (n=21, 20.8%), and osteoarticular infections (n=13, 12.9%). Pneumonia accounted for only six (5.9%) patients. The prevalence of nasal MRSA colonization was 6.9% (n=7). The sensitivity of the MNS test to predict a MRSA infection was 42.9% with a specificity of 95.7%. The positive predictive value (PPV) and negative predictive values (NPV) were 42.9% and 95.7%, respectively. In about half (55/95, 57.9%) of patients initiated on anti-MRSA therapy, these agents were discontinued during the admission. A quarter (n=14, 25.5%) were de-escalated based on the negative MNS test alone, and another third (n=21, 38.2%) after negative MNS test and negative culture results became available. ConclusionPediatric providers at this institution have started to use the MNS to help limit anti-MRSA therapy. We noted a high NPV which suggests that MNS may be useful for timely de-escalation of anti-MRSA therapy and thereby a useful antimicrobial stewardship tool for hospitalized children. Prospective studies to evaluate the utility of MNS for the various infectious syndromes are warranted.Disclosures All Authors: No reported disclosures

128. Development of an Analytics Dashboard to Monitor Antimicrobial Selection and Duration for Pneumonia

BackgroundAnalytical and visual tools can be used to monitor progress for a variety of ASP key performance indicators, but few data describe the process of building disease-state specific tools to retrospectively monitor antimicrobial choice and duration. We describe process and methods for development of a pneumonia dashboard.MethodsIn late 2019, the Carolina ASP began construction of a dashboard to monitor antimicrobial selection and duration in patients admitted with a diagnosis code (ICD-10) consistent with pneumonia. Data extracted from the medical record after discharge included: admission date and time, admission and discharge ICD-10s, inpatient orders and administrations for agents included in the NHSN Antimicrobial Use (AU) option, and antimicrobials ordered at discharge with associated ICD-10. Extracted data fields were validated using a one-month sample. Displays were constructed to trend selection during the first 48 hours of admission, inpatient days of therapy, and total length of therapy (sum of inpatient + outpatient days) for patients who received a discharge prescription for an antimicrobial included in the AU option that was associated with an ICD-10 consistent with pneumonia. Trends observed between Jan 2020 and Mar 2021 are reported. Results341 admissions were trended. Within the first two days of admission, monthly proportions of patients receiving an antimicrobial by category were: anti-MRSA therapies (vancomycin, linezolid), 0.20 to 0.75; broad spectrum beta-lactams (e.g., cefepime, pip/tazo), 0.40 to 0.81; CAP therapies (e.g., ceftriaxone, levofloxacin), 0.48 to 1.00 (Figure). Median inpatient duration of therapy was 5 days (IQR 3-8; range 1 to 68). Total length of therapy was median 6 days (IQR 4-10; range 1 to 68). Figure. Proportions of Patients Prescribed Antimicrobial Categories of Interest During the First 48 Hours of Admissions for Pneumonia. Legend: Anti-MRSA = vancomycin or linezolid; HAP abx = cefepime, piperacillin/tazobactam, ceftazidime, meropenem; CAP = ceftriaxone, azithromycin, ampicillin/sulbactam, amoxicillin/clavulanate, cefdinir, levofloxacin.ConclusionAutomated reports and visual tools can provide actionable insights for ASP practice. From this dashboard, we identified variable but high rates of anti-MRSA and broad-spectrum beta-lactam use within the first 48 hours of admission. The median inpatient and total length of therapy of 5 and 6 days, respectively, were similar to guideline-recommended durations. The up-front cost for building analytical tools can be substantial, but can be viewed as an investment if the metrics and methods are carefully selected. Disclosures All Authors: No reported disclosures

1319. Assessment of Spectrum Score-Based Antibiotic De-Escalation in Patients with Nosocomial Pneumonia

BackgroundHospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant morbidity and mortality. Guidelines recommend broad-spectrum empiric antibiotic therapy, including treatment for Pseudomonas aeruginosa (PSAR) and methicillin-resistant Staphylococcus aureus (MRSA), followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure.MethodsThis single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016–2019. Patients were enrolled if they met pre-defined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). Data were compared using chi-square, Mann-Whitney U, or T-tests. The primary outcome was composite treatment failure, defined as all-cause mortality or re-admission for pneumonia within 30 days of diagnosis, analyzed using a Cox proportional hazards analysis to control for confounding variables. Figure 1. Study Schematic Table 1. Spectrum Score Assignment ResultsOf 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs. 1026 NDE). Groups were well-matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs. 50.6%, P=0.011). Patients receiving DE experienced a 65% and 44% reduction in anti-MRSA and anti-PSAR therapies by day 3, respectively. There was no difference in composite treatment failure (35.0% DE vs. 33.8% NDE, P=0.604). DE was not associated with treatment failure on Cox multivariate regression analysis (HR 1.13, 95% CI 0.97-1.33, P=0.149). Patients receiving DE had fewer antimicrobial days (median 9 vs. 11, P< 0.0001), episodes of Clostridioides difficile (2.2% vs. 3.8%, P=0.046), and days of hospitalization (median 20 vs. 22 days, P=0.006).Figure 2: Median Spectrum Scores (SS) Days 0 to 28 Table 2: Cox Regression Analysis ConclusionDE and NDE resulted in similar rates of composite treatment failure at 30 days; however, DE was associated with fewer antimicrobial days, episodes of C. difficile, and days of hospitalization. Spectrum scores can objectively identify DE, but further studies are needed to fully understand their utility in this context.Disclosures Tamara Krekel, PharmD, BCPS, BCIDP, Merck (Speaker’s Bureau) David J. Ritchie, PharmD, BCPS (AQ-ID), AbbVie (Speaker’s Bureau)Merck (Speaker’s Bureau)

Utility of Methicillin-Resistant Staphylococcus aureus Nares Screening in Hospitalized Children with Acute Infectious Disease Syndromes.

Studies in adults support the use of a negative methicillin-resistant Staphylococcus aureus (MRSA) nares screening (MNS) to help limit empiric anti-MRSA antibiotic therapy. We aimed to evaluate the use of MNS for anti-MRSA antibiotic de-escalation in hospitalized children (<18 years). Records of patients admitted between 1 January 2015 and 31 December 2020 with a presumed infectious diagnosis who were started on anti-MRSA antibiotics, had a PCR-based MNS, and a clinical culture performed were retrospectively reviewed. A total of 95 children were included with a median age (range) of 2 (0–17) years. The top three diagnosis groups were skin and soft tissue infections (n = 38, 40%), toxin-mediated syndromes (n = 17, 17.9%), and osteoarticular infections (n = 14, 14.7%). Nasal MRSA colonization and growth of MRSA in clinical cultures was found in seven patients (7.4%) each. The specificity and the negative predictive value (NPV) of the MNS to predict a clinical MRSA infection were both 95.5%. About half (n = 55, 57.9%) had anti-MRSA antibiotics discontinued in-house. A quarter (n = 14, 25.5%) were de-escalated based on the negative MNS test alone, and another third (n = 21, 38.2%) after negative MNS test and negative culture results became available. A high NPV suggests that MNS may be useful for limiting unnecessary anti-MRSA therapy and thereby a useful antimicrobial stewardship tool for hospitalized children. Prospective studies are needed to further characterize the utility of MNS for specific infectious diagnoses.