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Objectives We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. Materials and methods Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. Results Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. Conclusions Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.

Background Asymptomatic bacteriuria is a common condition that is often treated unnecessarily with antimicrobials. Conditional urine reflex culturing leverages the negative predictive value of the absence of pyuria, often defined by a minimum urine white blood cell (WBC) count cutoff > 10 cells/hpf. This value has not been extensively validated. This study evaluated parameters from urinalysis (UA), including various WBC cutoffs, and their ability to detect urinary tract infections (UTIs). Methods Retrospective cohort study of adult patients with or without urinary catheters with at least one UA between July 2020 to July 2021. Conditional reflex urine culturing with urine WBC cutoff of > 10 cells/hpf was standard practice. Pregnant patients, patients with urologic procedures, and those who were mechanically ventilated at time of UA were excluded. UTIs were defined as definitive, probable, possible, or unlikely (Table 1). Comparisons between definitions and those with definitive/probable versus possible/unlikely UTIs were made using Chi-squared test. Table 1.UTI definitions Results 368 patients were included in the final analysis. 154 (41.8%) were male and mean age was 56.9 ± 17.9 years. 117 (31.8%) had urinary catheters. 296 (80.4%) of UAs were treated with antibiotics which were administered after UA collection 89.2% of the time. The total incidence of definitive, probable, possible, and unlikely UTIs according to WBC count is listed in Table 2. UA parameters including leukocyte esterase positivity and presence of nitrites did not differ when compared between definitive/probable versus possible/unlikely UTIs (94.3% vs. 97.1% and 23.9% vs 26.4% respectively). Differences in leukocyte esterase positivity and presence of nitrites were not seen for non-catheterized patients when compared between definitive/probable versus possible/unlikely UTIs (92.3% vs. 96.5% and 21.2% and 29.3% respectively). Table 2.Urine WBC categorization stratified by UTI definition Conclusion Urine WBC cutoff > 10 cells/hpf identifies many patients with unlikely UTIs. Current UA parameters do not definitively differentiate UTIs from not in catheterized or non-catheterized patients. Most patients with a positive UA were treated. Disclosures Kimberly C. Claeys, PharmD, BioFire Diagnostics: Honoraria.

Background Overdiagnosis of ventilator associated pneumonia (VAP) is common and may be due, in part, to excessive culturing of the respiratory tract in ventilated patients. We sought to evaluate the appropriateness of these cultures based on clinical characteristics leading to culture acquisition, and the relationship with antibiotic use. Methods We included mechanically ventilated adult patients in the Neuroscience and Cardiac Surgery Intensive Care Units at an academic medical center in Baltimore, MD, who had respiratory tract cultures obtained from March 1 to June 30, 2021. The appropriateness of respiratory cultures was evaluated by chart review in a standardized manner using a published algorithm (Figure 1). Clinical characteristics of patients with appropriate vs. inappropriate cultures were compared using Fisher’s exact test. Results 98 respiratory tract cultures (58 endotracheal aspirates, 25 mini bronchoalveolar lavages (BAL), 13 BALs, and 2 bronchial washings) were evaluated. Of these, 19 (19%) were deemed appropriate and 79 (81%) were inappropriate. Compared to patients with inappropriate cultures, those with appropriate cultures were more likely to demonstrate worsening oxygenation, new or increasing infiltrate on chest x-ray, or hemodynamic instability. The groups did not significantly differ with respect to fever or changes in WBC count (Figure 2). Of 79 inappropriate cultures, 31 (39%) received a clinical diagnosis of VAP from their provider. In 23 (29%) instances, antibiotics were started or changed based on culture results, and 9 (11%) were on empiric therapy for VAP that was continued unchanged. An additional 24 (30%) continued antibiotics not directed toward VAP. Excluding those on antibiotics not directed towards index respiratory culture results, patients received a median of 6 (IQR 2.5, 7) days of therapy. Conclusion A large majority of lower respiratory tract cultures in mechanically ventilated patients are potentially inappropriate and associated with overdiagnosis of VAP and unnecessary antibiotic exposure. Incorporating respiratory tract specific attributes into clinical decision making rather than “pan-culturing” for fever or leukocytosis may be an opportunity for diagnostic stewardship in this setting. Disclosures Kimberly C. Claeys, PharmD, BioFire Diagnostics: Honoraria.

Background Half of patients have cultures pending at discharge. Failure to address these results may delay diagnosis and time to appropriate antimicrobials. The purpose of the study is to evaluate appropriateness of antimicrobial therapy and result documentation in patients with positive cultures finalized post-discharge. Methods Retrospective cohort study of patients from 7/2019-12/2019 with positive sterile-site microbiologic cultures finalized post-discharge. Pertinent inclusion and exclusion factors were admission ≥48 hours and non-sterile sites, respectively. The primary objective was to determine the frequency of discharged patients warranting antimicrobial intervention based on finalized culture results. Secondary objectives included incidence and timeliness of result documentation and rates of 30-day hospital readmission, among intervention warranted vs not warranted. Chi-squared or Fisher’s exact tests were used as appropriate. Binary multivariable logistic regression was completed for 30-day hospital re-admission stratified by infectious disease (ID) team involvement. Results 208 of 768 patients screened were included. Most patients were discharged from a surgical service (45.7%); deep tissue and blood were the most common culture sites (29.3%). Antimicrobial intervention was warranted in 36.5% of patients (n=76). Rates of result documentation were overall low (35.5%). Time to documentation of results was significantly shorter in patients warranting intervention compared to those who did not, but hospital readmission was higher (Table 1). Finally, result documentation in patients not being followed by ID was associated with decreased odds of 30-day readmission (OR 0.19, 95% CI, 0.07-0.53) (Table 2). Conclusion A significant number of patients with cultures finalized post-discharge warranted antimicrobial intervention. Acknowledgment of final culture data can decrease the risk of 30-day hospital readmission, especially in patients not followed by ID. Quality improvement efforts should focus on methods to improve documentation and follow-up of pending cultures to improve patient outcomes. Disclosures Kimberly C. Claeys, PharmD, BioFire Diagnostics: Honoraria|La Jolla Pharmaceuticals: Advisor/Consultant.

Background: Intra-operative topical vancomycin (VAN) is a strategy used to prevent surgical site infections (SSI). Although evidence supporting efficacy in SSI prevention is evolving, data describi...

Background Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship. Methods A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen experts ranked recommendations on a 9-point Likert scale. Recommendations on which the panel did not reach agreement were discussed during a virtual meeting, then a second round of ranking by email was completed. After secondary review of results and panel discussion, a series of guidance statements was developed. Results One hundred and sixty-five questions were reviewed. The panel reaching agreement on 104, leading to 18 overarching guidance statements. The following strategies were recommended to optimize ordering urine cultures: requiring documentation of symptoms, sending alerts to discourage ordering in the absence of symptoms, and cancelling repeat cultures. For urine culture processing, conditional urine cultures and urine white blood cell count as criteria were supported. For urine culture reporting, appropriate practices included nudges to discourage treatment under specific conditions and selective reporting of antibiotics to guide therapy decisions. Conclusions These 18 guidance statements can optimize use of urine cultures for better patient outcomes.

Three rapid diagnostic test panels (Verigene BC-GN, BioFire BCID, and BCID 2 [RUO]) were compared using the Desirability of Outcome Ranking Management of Antimicrobial Therapy (DOOR-MAT) to evaluate potential downstream antimicrobial prescribing decisions resulting from the panels’ different organism and resistance detection. BioFire BCID 2 (RUO) had the best mean DOOR-MAT scores.

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.

Introduction Vancomycin remains first-line therapy for methicillin-resistant Staphylococcus aureus (MRSA) blood stream infections (BSI); however, its toxicity and reported clinical failures are well established. Binary efficacy endpoints evaluating alternative anti-MRSA therapies leave clinicians deciphering between segregated clinical and safety outcomes and do not provide a comprehensive patient-centered picture of comparative therapies. This study aimed to apply a novel methodology, desirability of outcomes ranking (DOOR), to compare anti-MRSA therapies. Methods This was a single-centered, retrospective, cohort of adult patients with MRSA BSI that received vancomycin, daptomycin, or ceftaroline. A previously developed DOOR for S. aureus BSI was adjusted and applied to this cohort to compare vancomycin-treated versus daptomycin/ceftaroline-treated patients. The DOOR had five mutually exclusive ranks: (1) alive without treatment failure, infectious complications, or grade 4 adverse events (AEs); (2) alive with any one of treatment failure, infectious complications, or grade 4 AE; (3) alive with two of treatment failure, infectious complications, or grade 4 AE; (4) alive with all three treatment failure, infectious complications, or grade 4 AE; or (5) deceased. Results A total of 43 vancomycin-treated and 13 daptomycin/ceftaroline-treated patients were included. Baseline clinical characteristics were similar, except for higher median serum creatinine in the daptomycin/ceftaroline cohort (0.76 [IQR 0.57, 1.11] vs 1.36 [IQR 1.09, 1.91] mg/dL, P = 0.03). Patients in the daptomycin/ceftaroline cohort had a 92% probability of better outcome using DOOR methodology. Patients treated with daptomycin/ceftaroline experienced less MRSA BSI persistence (0% vs 13.9%), MRSA BSI recurrence (7.8% vs 25.6%), grade 4 AEs (23.1% vs 46.5%), and in-hospital mortality (0% vs 9.3%). Conclusions Although limited by sample size, this study demonstrates the potential of DOOR to produce valuable, patient-centered results. Clinicians are encouraged to become familiar with appropriate use and interpretation of DOOR methodology as it will become an increasingly common endpoint in clinical trials.

This survey investigated diagnostic and antimicrobial stewardship practices related to molecular respiratory panel testing in adults with lower respiratory tract infections at acute care hospitals. Most respondents reported use of rapid respiratory panels, but related stewardship practices were uncommon and the real-world impact of respiratory panels were difficult to quantify.

Objectives To assess differences in vancomycin AUC estimates from two common, clinically applied first-order pharmacokinetic equation methods compared with Bayesian estimates. Methods A cohort of patients who received vancomycin and therapeutic drug monitoring was studied. First-order population pharmacokinetic equations were used to guide initial empirical dosing. After receipt of the first dose, patients had peak and trough serum levels drawn and steady-state AUC was estimated using first-order pharmacokinetic equations as standard care. We subsequently created a Bayesian model and used individual Empirical Bayes Estimates to precisely calculate vancomycin AUC24–48, AUC48–72 and AUC72–96 in this cohort. AUC at steady state (AUCSS) differences from the first-order methods were compared numerically and categorically (i.e. below, within or above 400–600 mg·h/L) to Bayesian AUCs, which served as the gold standard. Results A total of 65 adult inpatients with 409 plasma samples were included in this analysis. A two-compartment intravenous infusion model with first-order elimination fit the data well. The mean of Bayesian AUC24–48 was not significantly different from AUC estimates from the two first-order pharmacokinetic equation methods (P = 0.68); however, Bayesian AUC48–72 and Bayesian AUC72–96 were both significantly different when compared with both first-order pharmacokinetic equation methods (P Conclusions Bayesian-calculated AUCs between 48–72 and 72–96 h intervals were significantly different from first-order pharmacokinetic method-estimated AUCs at steady state. The various calculation methods resulted in different categorical classification, which could potentially lead to erroneous dosing adjustments in approximately half of the patients.

Background Prospective audit with feedback (PAF) is an impactful strategy for antimicrobial stewardship program (ASP) activities. However, because PAF requires reviewing large numbers of antimicrobial orders on a case-by-case basis, PAF programs are highly resource intensive. The current study aimed to identify predictors of ASP intervention (ie, feedback) and to build models to identify orders that can be safely bypassed from review, to make PAF programs more efficient. Methods We performed a retrospective cross-sectional study of inpatient antimicrobial orders reviewed by the University of Maryland Medical Center’s PAF program between 2017 and 2019. We evaluated the relationship between antimicrobial and patient characteristics with ASP intervention using multivariable logistic regression models. Separately, we built prediction models for ASP intervention using statistical and machine learning approaches and evaluated performance on held-out data. Results Across 17 503 PAF reviews, 4219 (24%) resulted in intervention. In adjusted analyses, a clinical pharmacist on the ordering unit or receipt of an infectious disease consult were associated with 17% and 56% lower intervention odds, respectively (adjusted odds ratios [aORs], 0.83 and 0.44; P ≤ .001 for both). Fluoroquinolones had the highest adjusted intervention odds (aOR, 3.22 [95% confidence interval, 2.63–3.96]). A machine learning classifier (C-statistic 0.76) reduced reviews by 49% while achieving 78% sensitivity. A “workflow simplified” regression model that restricted to antimicrobial class and clinical indication variables, 2 strong machine learning–identified predictors, reduced reviews by one-third while achieving 81% sensitivity. Conclusions Prediction models substantially reduced PAF review caseloads while maintaining high sensitivities. Our results and approach may offer a blueprint for other ASPs.

The role of follow-up blood cultures (FUBCs) in gram-negative bloodstream infections to improve clinical outcomes remains controversial, especially among immunocompromised patients. Among 139 patients, FUBCs were common (117, 84.2%); however, positive FUBCs were rare (3, 2.6%). Only presence of fever was associated with a positive FUBC.

Background Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin. Methods Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied. Results Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, –5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001). Conclusions No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.

Interrupted time series segmented regression was conducted to trend antibiotic use and multidrug-resistant gram-negative (MDRGN) acquisition relative to COVID-19 in an academic hospital. Total antibiotic use and antibiotic use related to pneumonia was higher in the period after the onset of COVID-19 compared to the similar calendar period in 2019. Furthermore, MDRGN acquisition increased 3% for every increase in positive COVID-19 tests per week.

Decisions regarding which rapid diagnostic test (RDT) for bloodstream infections to implement remain challenging given the diversity of organisms detected by different platforms. We used the desirability of outcome ranking management of antimicrobial therapy (DOOR-MAT) as a framework to compare two RDT platforms on potential desirability of antimicrobial therapy decisions. An observational study was performed at University of Maryland Medical System comparing Verigene blood culture (BC) to GenMark Dx ePlex blood culture ID (BCID) (research use only) panels on blood cultures from adult patients. Positive percent agreement (PPA) between each RDT platform and Vitek MS was calculated for comparison of on-panel targets. Theoretical antimicrobial decisions were made based on RDT results, taking into consideration patient parameters, antimicrobial stewardship practices, and local infectious diseases epidemiology. DOOR-MAT with a partial credit scoring system was applied to these decisions, and mean scores were compared across platforms using a paired t test. The study consisted of 160 unique patients. The Verigene BC PPA was 98.6% (95% confidence interval [CI], 95.1 to 99.8), and ePlex BCID PPA was 98% (95% CI, 94.3 to 99.6). Among the 31 organisms not on the Verigene BC panels, 61% were identified by the ePlex BCID panels. The mean (standard deviation [SD]) DOOR-MAT score for Verigene BC was 86.8 (28.5), while that for ePlex BCID was 91.9 (23.1) (P = 0.01). Both RDT platforms had high PPA for on-panel targets. The ePlex BCID was able to identify more organisms than Verigene, resulting in higher mean DOOR-MAT scores.

Background We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). Methods This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR). Results Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081–0.941). Conclusions Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs.

Introduction Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious processes seen in the clinical setting. For patients with complicated ABSSSIs deemed to require intravenous antibiotics, vancomycin remains the mainstay therapy. Ceftaroline has been shown to be non-inferior to vancomycin and may result in faster resolution of signs of infection. Methods Multicenter, prospective, open-label, randomized trial of ceftaroline versus vancomycin for the treatment of adult patients admitted for management of ABSSSIs from April 2012 to May 2016; 166 patients in the clinically evaluable (CE) group were needed to determine a 20% difference in primary outcome of clinical response at day 2 or 3 of antibiotics. Clinical response was defined as cessation of spread of lesion and improvement in systemic signs/symptoms of infection. A secondary outcome was a ≥ 20% reduction in lesion size at day 2 or 3 of antibiotics. Results One hundred seventy-four patients were enrolled in the intention-to-treat (ITT) group and 108 were CE. Among CE patients, 54 were randomized to ceftaroline and 54 to vancomycin. Baseline characteristics were similar except patients in the ceftaroline arm were older and had a non-significantly higher degree of comorbidities (median Charlson score 2 vs. 4, respectively). Cellulitis was the most common type of ABSSSI (85.2% vs. 79.6%, respectively). Rapid diagnostic testing of available cultures (n = 55) demonstrated high agreement with clinical microbiology for identification of Staphylococcus aureus (100%) and MRSA (100%). There was no significant difference in primary outcome of day 2 or 3 clinical response (50.0% vs. 51.9%). Conclusion Early clinical response between vancomycin- and ceftaroline-treated ABSSSIs was similar. Patients with ABSSSIs rarely remained hospitalized for > 2–3 days, thus limiting our ability to critically assess clinical outcomes. Trial Registration ClinicalTrials.gov identifier, NCT02582203. Funding Allergan plc.

Background Molecular rapid diagnostic tests (RDTs) for bloodstream infections (BSI) utilize a variety of technologies and differ substantially in organisms and resistance mechanisms detected. RDT platforms decrease time to optimal antibiotics; however, data on RDTs in special populations, such as immunocompromised are extremely limited. This study aimed to compare theoretical changes in antibiotics based on differences in panel identification of organisms and resistance targets among three commercially available RDT panels. Methods Retrospective cohort of immunocompromised patients treated for gram-negative BSI at University of Maryland Medical Center from January 2018 to September 2020. Immunocompromised was defined as active hematologic or solid tumor malignancy at time of BSI diagnosis, history of hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), or absolute neutrophil count (ANC) < 1000 cells/mm3 at any time 30 days prior to BSI diagnosis. Verigene BC-GN was performed as standard of care. GenMark ePlex BCID and BioFire FilmArray BCID 2 results were assigned based on respective identifiable organism panels. An infectious diseases clinician blinded to final antimicrobial susceptibility testing (AST) results used RDT results to assign antibiotic treatments for each platform. Decisions were referenced against a priori DOOR-MAT matrices. A partial credit scoring system (0 to 100) was applied to each decision based on final AST results. The mean and standard deviation (SD) were compared across panels using One-Way Repeated Measures ANOVA with modified Bonferroni for multiple comparisons. Results A total of 146 patients met inclusion. Baseline characteristics are summarized in Table 1. The mean (SD) DOOR-MAT scores for the three RDT panels were: 86.1 (24.4) Verigene BC-GN vs. 88.5 (22.2) GenMark BCID vs. 87.2 (24.4) BioFire BCID 2. There was no statistically significant difference between the panels for DOOR-MAT score (P=0.6). Table 1. Baseline Patient Characteristics and Organism Identification Conclusion Within an immunocompromised patient population, differences in organism identification between three commercially available RDT panels did not impact theoretical antibiotic prescribing. Disclosures J. Kristie Johnson, PhD, D(ABMM), GenMark (Speaker’s Bureau) Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)

Objective:In the absence of pyuria, positive urine cultures are unlikely to represent infection. Conditional urine reflex culture policies have the potential to limit unnecessary urine culturing. We evaluated the impact of this diagnostic stewardship intervention.Design:We conducted a retrospective, quasi-experimental (nonrandomized) study, with interrupted time series, from August 2013 to January 2018 to examine rates of urine cultures before versus after the policy intervention. We compared 3 intervention sites to 3 control sites in an aggregated series using segmented negative binomial regression.Setting:The study included 6 acute-care hospitals within the Veterans’ Health Administration across the United States.Participants:Adult patients with at least 1 urinalysis ordered during acute-care admission, excluding pregnant patients or those undergoing urological procedures, were included.Methods:At the intervention sites, urine cultures were performed if a preceding urinalysis met prespecified criteria. No such restrictions occurred at the control sites. The primary outcome was the rate of urine cultures performed per 1,000 patient days. The safety outcome was the rate of gram-negative bloodstream infection per 1,000 patient days.Results:The study included 224,573 urine cultures from 50,901 admissions in 24,759 unique patients. Among the intervention sites, the overall average number of urine cultures performed did not significantly decrease relative to the preintervention period (5.9% decrease; P = 0.8) but did decrease by 21% relative to control sites (P < .01). We detected no significant difference in the rates of gram-negative bloodstream infection among intervention or control sites (P = .49).Conclusions:Conditional urine reflex culture policies were associated with a decrease in urine culturing without a change in the incidence of gram-negative bloodstream infection.

Revised breakpoints for cefazolin (CFZ) against Enterobacterales may be difficult to implement with current automated susceptibility testing platforms and could falsely report organisms as susceptible, leading to inappropriate treatment for bloodstream infections (BSI). This was a retrospective cohort of adult patients with Enterobacterales BSI reported CFZ susceptible per Vitek®2. The primary outcome was the percentage susceptible by minimum inhibitory concentration (MIC) Gradient Test Strips and disk diffusion. Secondary outcomes included clinical outcomes between CFZ and non–CFZ-treated patients. Among 195 isolates reported CFZ-susceptible per Vitek®2, 84 (43.1%) were CFZ susceptible by MIC Gradient Test Strips vs 119 (61%) by disk diffusion. No difference was noted in 30-day all-cause mortality, secondary complications, or 30-day readmissions. Treatment failure was less likely to occur with source control (adjusted OR 0.06) and infectious disease consult (adjusted OR 0.37). There was a large degree of discrepancy between automated testing and manual methods; the clinical impact of this discrepancy warrants further investigation.

Background Verigene Blood-Culture Gram-Negative is a rapid diagnostic test (RDT) that detects gram-negatives (GNs) and resistance within hours from gram stain. The majority of the data support the use of RDTs with antimicrobial stewardship (AMS) intervention in gram-positive bloodstream infection (BSI). Less is known about GN BSI. Methods This was a retrospective quasi-experimental (nonrandomized) study of adult patients with RDT-target GN BSI comparing patients pre-RDT/AMS vs post-RDT/pre-AMS vs post-RDT/AMS. Optimal therapy was defined as appropriate coverage with the narrowest spectrum, accounting for source and co-infecting organisms. Time to optimal therapy was analyzed using Kaplan-Meier and multivariable Cox proportional hazards regression. Results Eight-hundred thirty-two patients were included; 237 pre-RDT/AMS vs 308 post-RDT/pre-AMS vs 237 post-RDT/AMS, respectively. The proportion of patients on optimal antibiotic therapy increased with each intervention (66.5% vs 78.9% vs 83.2%; P Conclusions With the introduction of RDT and AMS, both proportion and time to optimal antibiotic therapy improved, especially among those with an existing ID consult. This study highlights the beneficial role of RDTs in GN BSI.

Hospital-based antibiotic stewardship (AS) programs provide oversight and guidance for appropriate antimicrobial use in acute care settings. Infectious disease expertise is beneficial in the care of hospitalized patients with infections. The impact of infectious diseases consultation (IDC) on antimicrobial appropriateness in a large tertiary hospital with an established AS program was investigated. This was a cross-sectional study from October 2017 to March 2019 at a large academic hospital with an AS-directed prospective audit and feedback process and multiple IDC services. Antimicrobial appropriateness was adjudicated by an AS team member after antimicrobial start. Antimicrobial appropriateness was compared among antimicrobial orders with and without IDC using propensity score matching and multivariable logistic regression. Analyses were stratified by primary services caring for the patients. There were 10,508 antimicrobial orders from 6,165 unique patient encounters. Overall appropriateness was 92%, with higher appropriateness among patients with IDC versus without IDC (94% versus 84%; P

Eravacycline (ERV) was used in 35 patients for various infections. The most common pathogen was Klebsiella pneumoniae, and 30-day survival was 74%. Absence of 30-day recurrence and resolution of signs and symptoms of infection were 91% and 57%, respectively. ERV was well-tolerated, with adverse events leading to drug discontinuation in one patient.

Background Urine cultures are often positive in the absence of a urinary tract infection (UTI). Pyuria is generally considered necessary to diagnose a UTI. Problem Urine cultures are often positive in the absence of UTI leading to unnecessary antibiotics. Methods Quasi-experimental pre-post study of all patient urine cultures ordered in a VA acute care hospital, emergency department (ED), and two long-term care (LTC) facilities from August 2016 to August 2018. Urine cultures performed per 100 days were compared pre- (August 2016 to July 2017) versus post-intervention (August 2017 to August 2018) using interrupted time series negative binomial regression. Intervention We examined whether reflexing to urine culture only if a urinalysis (UA) found greater than 10 WBC/hpf decreased urine culturing. Results In acute-care, reflex culturing resulted in a 39% time series regression analysis adjusted decrease in the rate of cultures performed (pre-intervention, 3.6 cultures/100 days vs. Post-intervention, 1.8 cultures/100 days, p p = 0.0015) regression analysis adjusted decrease in cultures, from 5.4/100 visits to 3.3/100 visits. In LTC, there was a small absolute, but regression analysis adjusted increase of 89% (p = 0.0018) in rates from (0.4/100 days to 0.5/100 days). Conclusion In acute care and ED, urine reflex culturing decreased the number of urine cultures performed. A small absolute increase was seen between pre-post time periods in LTC. Reflex testing generally decreases cultures and may lead to more accurate diagnoses of CAUTI.

Resistant gram-negative infections are becoming increasingly difficult to treat, prompting increased focus on drug development. This review will focus primarily on the new beta-lactam agents developed in the past 5 years that target multidrug-resistant (MDR) gram-negative organisms, including those producing carbapenemases. Four new agents including ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MER-VAB), imipenem-relebactam (IMI-REL), and cefiderocol have recently been approved for the treatment of resistant gram-negative infections. CAZ-AVI remains an option for blaOXA-48–producing isolates and potentially MDR Pseudomonas aeruginosa, but the concern for resistance arises when using the agent for KPC-producing Enterobacteriales. MER-VAB appears to be more stable than CAZ-AVI in the treatment of KPC-producing Enterobacteriales but less is known about its propensity for the development of resistance and the drug does not reliably expand the coverage of meropenem-resistant P. aeruginosa isolates. IMI-REL expands the spectrum of imipenem-cilastatin to include KPC-producing Enterobacteriales as well as MDR P. aeruginosa but much less is known about its real-world clinical utility. Cefiderocol is the only of the four new agents with efficacy against metallo-beta-lactamases and resistant Acinetobacter species, but comparator studies using best available therapy for carbapenem-resistant gram-negative bacterial infections show higher mortality rates with the new drug, making its role in clinical therapy still to be determined. The new beta-lactams differ in their mechanisms of combatting resistance and thus have unique roles in therapy. Additional evidence is needed regarding the potential for development of resistance in the newer combination agents, as well as for the role of cefiderocol in carbapenem-resistant gram-negative infections.

Introduction Acute bacterial skin and skin structure infections (ABSSSIs) represent a large burden to the US healthcare system. There is little evidence-based guidance regarding the appropriate level of care for ABSSSIs. This study aimed to develop a prediction model and risk-scoring tool to determine appropriate levels of care. Methods This was a single-center observational cohort study of adult patients treated for ABSSSIs from 2012 to 2015 at the Detroit Medical Center. The predictive model used to create a novel risk-scoring tool was derived using multinomial regression analysis. The overall accuracy of this tool was compared to the Clinical Resource Efficacy Support Team (CREST) Classification and Standardized Early Warning Score (SEWS) using area-under-the- receiver-operator-curve (AUROC) analysis and Z-statistic. Results Final patient disposition was 230 (45.5%) home from the emergency department (ED), 65 (12.8%) observation unit (OU), and 211 (41.7%) initial inpatient. IV antibiotic therapy was used in 358 (70.8%) patients. CREST and SEWS were not accurate in the determination of ED versus OU disposition [AUROC CREST 0.0.682 (95% CI 0.640–0.724), AUROC SEWS 0.686 (95% CI 0.641–0.731)], but performed better in determining ED/OU versus inpatient [AUROC CREST = 0.678 (95% CI 0.630–0.725), AUROC SEWS 0.693 (95% CI 0.645–0.740)]. These scores were also not accurate in determining IV versus PO antibiotic therapy [AUROC CREST = 0.586 (95% CI 0.530–0.624), AUROC SEWS = 0.630 (95% CI 0.576–0.684)]. A risk-scoring tool ranging from 0 to 10 points was derived incorporating WBC, temperature, site of infection, and past medical history of diabetes, liver disease, PVD, AKI, and/or CKD. The AUROC of the new model was 0.675 (95% CI 0.611–0.739) ED versus OU, 0.789 (95% CI 0.748–0.829) ED/OU versus inpatient, and 0.742 (95% CI 0.694–0.789) IV versus oral antibiotics. The new score had a significantly higher AUROC compared to both the CREST and SEWS for determining ED/OU versus inpatient (p

Introduction Vancomycin remains the standard of care for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Treatment failures from heteroresistant vancomycin-intermediate subpopulations (hVISA) are challenging to detect. Minimum inhibitory concentrations (MIC) identified by modified population analysis profile (PAP) is an alternative testing method. The aim of this study was to evaluate the role of PAP MIC on vancomycin failures in two high inoculum infections: MRSA infective endocarditis and pneumonia. Methods Retrospective, observational study at Detroit Medical Center from 2008 to 2016. Adults ≥ 18 years with ≥ 1 positive MRSA blood culture from IE or pneumonia source and received ≥ 48 h vancomycin were included. The primary outcome was composite failure: MRSA bacteremia ≥ 7 days or 30-day all-cause mortality. Results A total of 191 patients were included; 47.6% IE and 52.4% pneumonia. About 19% were hVISA isolates, median vancomycin PAP MIC of 3 (2, 3). More than half (54.5%) experienced composite failure with a larger proportion of PAP MIC ≥ 4 mg/L in this group (25 vs. 15%, p = 0.086). Patients with IE experienced prolonged bacteremia whereas patients with pneumonia experienced higher 30-day mortality. On logistic regression analysis, age [adjusted odds ratio (aOR), 1.026; 95% confidence interval (CI), 1.005–1.047; p = 0.014] and APACHE II score (aOR 1.039; 95% CI, 1.004–1.076; p = 0.029) independently predicted composite failure. Conclusion Vancomycin PAP MIC may be a more relevant predictor of patient outcomes in persistent bacteremic MRSA infections (e.g., IE). This susceptibility method is less applicable in other high inoculum infections with shorter bacteremia durations and higher mortality rates (e.g., pneumonia).

Objectives Staphylococcus aureus bacteremia (SAB) is an important cause of morbidity and mortality. Suboptimal treatment has been associated with poor patient outcomes. Our antimicrobial stewardship program (ASP) evaluated SAB management based on predefined performance measures both prior to and after instituting a "care package" intervention led by clinical pharmacists and infectious diseases physicians. The primary outcome included a 4-point "optimal care score" (OCS) consisting of targeted antibiotic therapy within 24hours, repeating blood cultures, antibiotic duration assessment, and appropriate duration of therapy. The presence of an ID consult, SAB readmission and mortality were also assessed. Methods This was a quasi-experimental, propensity score matched study of SAB management. Adult patients were retrospectively evaluated from October 2011 – October 2012, and intervention took place from November 2013 – December 2015. Intervention consisted of a clinical pharmacist contacting the primary team after identification of SAB to recommend (1) appropriate antibiotics within 24hours, (2) repeat blood cultures to document clearance, (3) assessment for metastatic infection, (4) and appropriate duration of therapy. These constituted the 4-point OCS. ID consult was also recommended. Patients were propensity score matched 1:2 based on age, diabetes, presence of hardware, methicillin-resistant S. aureus (MRSA) isolate, and stratified infectious source. Patients ≥18 with SAB were included. Results Intervention was associated with improved adherence to each metric within the OCS, and more patients in the intervention cohort achieved a perfect OCS of 4. Intervention was associated with a lower rate of readmission and mortality. Conclusion A pharmacist-driven, ASP intervention on SAB therapy was associated with increased adherence to core SAB care metrics and reduced relapse and mortality.

Background Recent vancomycin (VAN) guidelines recommend targeting an area under the curve (AUC) concentration of 400-600 for treatment of methicillin resistant Staphylococcus aureus infections. Multiple strategies for calculating AUC exist, including first order pharmacokinetic (foPK) equations and Bayesian models. Most clinical applications of foPK assume unchanged patient status and project ideal administration times to estimate exposure. Bayesian modeling provides the best estimate of true drug exposure and can incorporate changing patient covariates and exact doses. We compared two commonly used foPK methods to Bayesian estimates of VAN AUC. Graphs depict calculated AUCs using the three different methods: 1) Population PK estimated (foPOPPK) 2) Two-level first dose estimated (foFDPK) 3) Bayesian estimated. Methods First order equations were performed using population PK estimates (foPOPPK) to estimate steady state (SS) AUC and initial doses. Two concentrations after first dose were used to estimate SS AUC (foFDPK). A 2-compartment Bayesian model allometrically scaled for weight and adjusted for creatinine clearance was used to determine 24-48 hour AUCs. Differences between AUCs were compared using a mixed-effects analysis, and correlation of foPK equations to Bayesian estimates was described using Spearman’s correlation. Patient results from each method were classified as below (< 400), within (400-600), or above ( >600) targets. Results 65 adult patients were included. The median and IQR for calculated AUCs using foPOPPK, foFDPK, and Bayesian methods were 495.6 (IQR: 76.6), 498.2 (IQR: 107.4), and 472.1 (IQR: 177.9), respectively with p >0.65 for both foPK methods vs. the Bayesian method. AUCs predicted by foPK equations were poorly correlated with Bayesian AUCs (Spearman’s rho= -0.08, p=0.55), while AUCs from foFDPK better correlated with Bayesian AUCs (Spearman’s rho= 0.48, p=0.00). AUCs were within, above, and below target for 54%, 20%, and 26% for the Bayesian model; 95%, 5% and 0% for foPOPPK; and 74%, 12%, and 14% for foFDPK. foPK AUC estimates concurred with Bayesian estimates only 52% of the time. Conclusion AUCs calculated by the three methods did not differ on average, but dosing recommendations for foPK at the patient level varied substantially compared to the Bayesian method. This difference is because Bayesian estimation incorporates actual patient exposures while foPK equations rely on idealized dose timing to predict AUCs. Disclosures Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau) Marc H. Scheetz, PharmD, MSc, Nevakar (Grant/Research Support)SuperTrans Medical (Consultant)US Patent #10688195B2 (Other Financial or Material Support, Patent holder)

Background Patients with COVID-19 receive high rates of antibiotic therapy, despite viral origin of infection. Reports of bacterial coinfection range from 3.5 to 8% in the early phase of infection. This study aimed to evaluate the relationship between diagnostic tests and antibiotic utilization in patients admitted with COVID-19 at the University of Maryland Medical Center to better inform future prescribing practices. Methods Retrospective cohort study of adult patients with a positive SARS-CoV-2 PCR on admission from March 2020 through June 2020. Associations between diagnostic tests employed and antibiotic initiation and duration were explored using bivariate analysis (SPSS®). Results Baseline characteristics of 224 included patients are reported in Table 1. Excluding SARS-CoV-2 PCRs, most frequently performed diagnostic tests included blood cultures (65.6%), MRSA nasal surveillance (45.1%), respiratory cultures (36.2%), respiratory viral panel (RVP) (33.0%), and Legionella (28.6%) and pneumococcal (26.3%) urine antigens. Positivity of RVP, Legionella, pneumococcus, blood, and respiratory tests were low (1.3%, 0.4%, 0.9%, 1.8%, and 6.7%, respectively). A total of 62% of patients were initiated on antibacterial therapy with a median cumulative antibiotic duration of 77.9 hours (IQR 41.4, 111.8). History of chronic respiratory disease (76% vs. 58.6%; P=0.025), any degree of oxygen requirement on admission (72% vs. 42.6%; P=0.006), and performance of blood cultures (70.7% vs. 46.8%, P< 0.0001) were associated with antibiotic initiation. Positive bacterial diagnostic respiratory culture (median duration 72.8h [IQR 46.7, 96.6] vs. 97.3h [IQR 79.8, 194.1]; P=0.027) and positive blood culture (median duration 80.1h [IQR 42.1, 111.7] vs. 97.5h [IQR 71.8, 164.8]; P=0.046) were associated with longer antibiotic duration. Patients who did not have respiratory cultures performed had similar antibiotic durations as those with negative respiratory cultures. Table 1. Baseline Characteristics Conclusion Despite low coinfection rates, negative diagnostic tests did not result in shorter empiric antibacterial duration. These findings highlight the ongoing need for both diagnostic and antimicrobial stewardship in COVID-19. Disclosures Emily Heil, PharmD, MS, BCIDP, Nothing to disclose Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)

Background The Clinical and Laboratory Standards Institute (CLSI) lowered MIC breakpoints for many beta-lactam antibiotics to enhance detection of resistance among Enterobacterales. This shift was also meant to eliminate the need for routine testing for extended-spectrum beta-lactamases (ESBLs). The recommended treatment for ESBL-producing Enterobacterales is carbapenems. The IDSA guidelines for MDR-GN organisms recommend using ceftriaxone (CRO) resistance as a proxy for ESBL production and thus carbapenem treatment. Under CLSI guidelines, alternative beta-lactams such as ceftazidime (CAZ) and cefepime (FEP) may still be reported as susceptible and thus used by clinicians even in light of IDSA recommendations. The aim of this project was to characterize the MIC distributions of CAZ and FEP stratified by CRO susceptibility. Methods Clinical E. coli, K. pneumoniae, and K. oxytoca isolates from blood cultures in adult patients from Nov 2016-Dec 2018 that had MICs tested by the Vitek-2 automated susceptibility testing system for CRO, FEP and CAZ were identified. Descriptive statistics were used to compare MIC distributions across the antibiotics of interest (SPSS). Results 573 isolates were included, of these, 17.3% were CRO resistant. Most (53%) CRO-R isolates had FEP MICs ≤2 which is considered susceptible per CLSI; 19% had FEP MICs of 4-8 which would be considered S-DD by CLSI (Figure 1A; breakpoints noted by dashed lines). Using the EUCAST breakpoint of ≤1, only 11% of CRO-R isolates would be reported as FEP-S. For CAZ, 40% of CRO-R isolates had CAZ MICs ≤4, which is considered S by CLSI. Using the EUCAST breakpoint of ≤1, only 12% of CRO-R isolates would be reported as CAZ-S (Figure 1B). Cefepime MIC Distribution for Ceftriaxone Resistant Isolates Distribution of MICs for cefepime for ceftriaxone resistant isolates with the breakpoints for EUCAST and CLSI noted with a dashed line Ceftazidime MIC Distribution for Ceftriaxone Resistant Isolates Distribution of MICs for ceftazidime for ceftriaxone resistant isolates with the breakpoints for EUCAST and CLSI noted with a dashed line Conclusion Half of CRO-R E. coli, K. pneumoniae and K. oxytoca have FEP and CAZ MICs at or below the current CLSI breakpoints. This may lead to their use for serious ESBL infections where a carbapenem is preferred. To prevent unnecessary use, laboratories should consider suppressing FEP and CAZ susceptibilities when CRO-R or adopting more the aggressive EUCAST breakpoints for these agents. Disclosures Emily Heil, PharmD, MS, BCIDP, Nothing to disclose Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)

Background Routine follow-up blood cultures (FUBC) are strongly recommended for Staphylococcus aureus and Candida spp. bloodstream infections (BSI), but the role of FUBC in Gram-negative (GN) BSI remains controversial. Factors that may result in persistent GN BSI include critical illness, endovascular infection, lack of source control, multidrug resistant organisms (MDRO), end-stage renal disease, or immunocompromised status. As such, FUBC in patients with any of these factors may be warranted to improve clinical outcomes, but the true balance of benefit versus harm remains unknown. Our objective was to evaluate the role of FUBC in immunocompromised patients with GN BSI. Methods This was a retrospective observational cohort of adult, immunocompromised patients treated for confirmed GN BSI between January 2019 and December 2020 at University of Maryland Medical Center. Immunocompromise was defined as active hematologic or solid tumor malignancy at time of BSI diagnosis, history of hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), or absolute neutrophil count (ANC) < 1000 cells/mm3 at any time 30 days prior to BSI diagnosis. FUBC were defined as blood cultures drawn between 24 hours and 7 days from index blood culture, within the same hospital encounter. Positive FUBC was defined as a FUBC with same pathogenic GN organism identified. Comparison of patient and microbiologic characteristics was made between patients with and without FUBC. Results A total of 146 patients with GN BSI were included. Baseline characteristics are reported in Table 1. FUBC were collected in 129 (88.4%) patients. Neutropenia (49.6% vs. 19.4%, P=0.122), presence of central line (69.8% vs. 30.2%, P=0.061), and hospital-acquired origin of BSI (63.6% vs. 36.4%, P=0.395) resulted in increased frequency of FUBC. Patients with FUBC had a significantly longer post-BSI mean (SD) length of stay (17.3 [35.4] vs. 6.5 [6.0] days; P=0.005). Positive FUBC occurred in only 2 cases (1.4%) and both patients had persistent fevers at time of FUBC. Table 1. Baseline Characteristics Conclusion Positive FUBC were uncommon in this immunocompromised cohort with GN BSI, which challenges the need for routine collection of FUBC in this patient population. Disclosures Ciera L. Bernhardi, PharmD, Servier Pharmaceuticals (Advisor or Review Panel member) J. Kristie Johnson, PhD, D(ABMM), GenMark (Speaker’s Bureau) Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)

Background Eravacycline (ERV) is approved in the United States (US) for the treatment of complicated intra-abdominal infections in adults. We aimed to evaluate the independent predictors of clinical success in patients treated with ERV for various infections. Methods Multicenter, retrospective, observational study conducted from September, 2018 to April, 2021. We included adults treated with ERV for ≥ 72hours. Clinical success was defined as 30-day survival, lack of 30-day infection-recurrence, and resolution of infection signs/symptoms. All outcomes were measured from ERV initiation. Multivariable logistic regression (MLR) was performed to identify independent predictors of clinical success. Clinically relevant variables were selected for model entry based on bivariate comparisons (P< 0.2) in a backward fashion. Results We included 223 patients from 16 medical centers in 13 geographically unique states. The median (IQR) age was 61 (50-69) years, 57% were male and 62% were Caucasian. Median (IQR) APACHE II, and Charlson Comorbidity scores were 15 (10-21), and 3 (1-5), respectively. Sources of infection were primarily intra-abdominal (27%) and respiratory (27%). Common pathogens included Acinetobacter baumannii (21%) and those of the Enterobacterales order (36%). Infectious diseases consultation and surgical interventions were obtained in 93.7% and 52% respectively. Clinical success occurred in 64%, specifically 30-day survival in 78%, absence of 30-day infection-recurrence in 93%, and 74% experienced resolution of infection signs/symptoms. Since characteristics and outcomes were similar among various pathogens, MLR was conducted using the overall cohort. Skin as a source and combination therapy with ERV were independently associated with higher clinical success: odds ratio 3.3 [CI 1.1-10.2] and 2.9 [1.4-5.9], respectively. Whereas, ICU admission at culture time and undergoing surgery within 30 days of culture were independently associated with reduced odds of clinical success: 0.4 [0.17-0.80] and 0.3 [0.11-0.63] respectively. Conclusion Although most ERV treated patients experienced clinical success, factors independently associated with higher clinical success are crucial to consider for optimum antibiotic selection. Disclosures Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau) Madeline King, PharmD, tetraphase (Speaker’s Bureau) Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Bruce M. Jones, PharmD, BCPS, Abbvie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)La Jolla (Speaker’s Bureau)Melinta (Consultant)Merck (Consultant)Paratek (Consultant, Speaker’s Bureau) Susan L. Davis, PharmD, Nothing to disclose Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

Introduction Lower respiratory tract infections (LRTIs) are a major cause of morbidity and death. Because of changes in how LRTIs are defined coupled with the increasing prevalence of drug resistance, there is a gap in knowledge regarding the current burden of antimicrobial use for Centers for Disease Control and Prevention (CDC)-defined LRTIs. We describe the infection characteristics, antibiotic consumption, and clinical and economic outcomes of patients with Gram-negative (GN) LRTIs treated in intensive care units (ICUs). Methods This was a retrospective, observational, cross-sectional study of adult patients treated in ICUs at two large academic medical centers in metropolitan Detroit, Michigan, from October 2013 to October 2015. To meet the inclusion criteria, patients must have had CDC-defined LRTI caused by a GN pathogen during ICU stay. Microbiological assessment of available Pseudomonas aeruginosa isolates included minimum inhibitory concentrations for key antimicrobial agents. Results Four hundred and seventy-two patients, primarily from the community (346, 73.3%), were treated in medical ICUs (272, 57.6%). Clinically defined pneumonia was common (264, 55.9%). Six hundred and nineteen GN organisms were identified from index respiratory cultures: P. aeruginosa was common (224, 36.2%), with 21.6% of these isolates being multidrug resistant. Cefepime (213, 45.1%) and piperacillin/tazobactam (174, 36.8%) were the most frequent empiric GN therapies. Empiric GN therapy was inappropriate in 44.6% of cases. Lack of in vitro susceptibility (80.1%) was the most common reason for inappropriateness. Patients with inappropriate empiric GN therapy had longer overall stay, which translated to a median total cost of care of $79,800 (interquartile range $48,775 to $129,600) versus $68,000 (interquartile range $38,400 to $116,175), p = 0.013. Clinical failure (31.5% vs 30.0%, p = 0.912) and in-hospital all-cause mortality (26.4% vs 25.9%, p = 0.814) were not different. Conclusion Drug-resistant pathogens were frequently found and empiric GN therapy was inappropriate in nearly 50% of cases. Inappropriate therapy led to increased lengths of stay and was associated with higher costs of care.

Intensive care unit (ICU) admission is a risk for multidrug-resistant (MDR) Pseudomonas aeruginosa, but factors specific to critically ill pneumonia patients are not fully characterized. Objective was to determine risk factors associated with MDR P. aeruginosa pneumonia among ICU patients. This was a retrospective case-control study of P. aeruginosa pneumonia in the ICU; cystic fibrosis and colonizers were excluded. Risk factors included comorbid conditions and prior healthcare exposure (anti-pseudomonal antibiotics, hospitalizations, nursing home, P. aeruginosa colonization/infection, mechanical ventilation). Of 200 patients, 47 (23.5%) had MDR P. aeruginosa pneumonia. Independent predictors for MDR were ≥24h antibiotics in the preceding 90days (carbapenems, fluoroquinolones, and piperacillin-tazobactam) (odds ratio, 3.6 [95% CI, 1.6-8.1]) and nursing home residence (2.3 [1.1-4.9]). MDR P. aeruginosa remains prevalent among ICU patients with pneumonia. Given poor outcomes with delayed therapy, patients should be thoroughly assessed for prior anti-pseudomonal antibiotic exposure and nursing home residency.

Background Timely effective therapy in multi-drug resistant (MDR) Pseudomonas (PsA) infections has a direct impact on patient survival. We aimed to determine the impact of diagnostic and antimicrobial stewardship (AMS) on time-to-appropriate therapy (TAP) and clinical outcomes of patients with MDR PsA infections utilizing novel beta-lactam/beta-lactamase inhibitors (BL/BLIs). Methods Retrospective cohort study of adult patients with MDR PsA infections at a 1,500-bed University-affiliated public hospital in Miami, Florida who received ≥72 hours of ceftazidime-avibactam (C/A) or ceftolozane-tazobactam (C/T). During the pre-intervention period (12/2017-12/2018), additional susceptibilities for C/A and C/T were performed upon providers’ request. In the post intervention period (01/2019 – 12/2019), we implemented automatic reflex algorithms (Figure 1) for faster identification and susceptibilities for MDR PsA, including carbapenemase producers. Results were communicated in real-time to the AMS team. Figure 1. Reflex Testing Algorithm for MDR Pseudomonas Isolates from Any Source Results Seventy-six patients were included; median age was 56 years (IQR 37.5–67.0), 40 (52.6%) were in an intensive care unit at time of culture collection; median APACHE II score was 20 (IQR 15.0 – 26.0). Three isolates were carbapenemase producers (VIM = 2; KPC = 1). The most common infections were pneumonia (56.6%) and bacteremia (18.4%). We found a significant decrease in median TAP (120.1 [IQR 82.5–164.6] vs 75.9 [IQR 51.3–101.7] hours, p = 0.003). Median time from culture collection to final susceptibility results was shorter in the post-intervention group (122.2 vs 90.5 hours; p < 0.001). Median length-of-stay after culture collection was numerically lower in the post-intervention group (26.0 [11.6–59.4] vs 19.7 [12.9–37.8] days; p = 0.33). Controlling for ICU admission, our intervention was not associated with decreased 30-day inpatient mortality (OR = 1.62, 95% CI 0.45–5.79). Conclusion Our study identified an improvement in TAP in MDR PsA infections with implementation of diagnostic and AMS initiatives. In an adequately powered study, our intervention could potentially impact patient survival through timely initiation of effective therapy with novel BL/BLIs. Disclosures All Authors: No reported disclosures

Ventilator-associated pneumonia (VAP) is one of the most common infections in the ICU. Prompt diagnosis is vital as mortality increases with delayed antibiotic therapy. However, accurate diagnosis is challenging due to non-specific clinical features in a complicated patient cohort. Microbiological culture data remains a crucial aspect in confirming diagnosis. Literature data comparing the benefit of invasive respiratory sampling to non-invasive is inconclusive. Differences in culturing practices translate in overidentification of organisms of unclear significance. Positive culture data in a low pre-test probability does not differentiate between true infection and colonization resulting in overtreatment. Furthermore, there are also opportunities for modifying the reporting of respiratory tract cultures that can better guide antimicrobial therapy. Under the umbrella of antimicrobial stewardship, diagnostic stewardship can be incorporated to create a systematic approach that would target culturing practices to match the right pre-test probability. Ideal outcome will be targeting cultures to the right patient population and minimizing unnecessary treatment.

The objective of this study was to determine if real-world ceftaroline treatment in adults hospitalized for acute bacterial skin and skin structure infections (ABSSSI) is associated with decreased infection-related length of stay (LOS(inf)) compared to that with vancomycin. This was a retrospective, multicenter, cohort study from 2012 to 2017. Cox proportional hazard regression, propensity score matching, and inverse probability of treatment weighting (IPTW) were used to determine the independent effect of treatment group on LOS(inf). The patients were adults hospitalized with ABSSSI and treated with ceftaroline or vancomycin for ≥72 h within 120 h of diagnosis at four academic medical centers and two community hospitals in Arizona, Florida, Michigan, and West Virginia. A total of 724 patients were included (325 ceftaroline treated and 399 vancomycin treated). In general, ceftaroline-treated patients had characteristics consistent with a higher risk of poor outcomes. The unadjusted median LOS(inf) values were 5 (interquartile range [IQR], 3 to 7) days and 6 (IQR, 4 to 8) days in the vancomycin and ceftaroline groups, respectively (hazard ratio [HR], 0.866; 95% confidence interval [CI], 0.747 to 1.002). The Cox proportional hazard model (adjusted HR [aHR], 0.891; 95% CI, 0.748 to 1.060), propensity score-matched (aHR, 0.955; 95% CI, 0.786 to 1.159), and IPTW (aHR, 0.918; 95% CI, 0.793 to 1.063) analyses demonstrated no significant difference in LOS(inf) between groups. Patients treated with ceftaroline were significantly more likely to meet criteria for discharge readiness at day 3 in unadjusted and adjusted analyses. Although discharge readiness at day 3 was higher in ceftaroline-treated patients, LOS(inf) values were similar between treatment groups. Clinical and nonclinical factors were associated with LOS(inf).

Background We conducted this study to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam (CZA) for a range of multidrug-resistant Gram-negative (MDR-GN) infections. Methods This is a multicenter, retrospective cohort study conducted at 6 medical centers in the United States between 2015 and 2019. Adult patients who received CZA (≥72 hours) were eligible. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of infection on CZA. Results In total, data from 203 patients were evaluated. Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas spp were isolated from 117 (57.6%) and 63 (31.0%) culture specimens, respectively. The most common infection sources were respiratory (37.4%), urinary (19.7%), and intra-abdominal (18.7%). Blood cultures were positive in 22 (10.8%) patients. Clinical failure, 30-day mortality, and 30-day recurrence occurred in 59 (29.1%), 35 (17.2%), and 12 (5.9%) patients, respectively. On therapy, CZA resistance developed in 1 of 62 patients with repeat testing. Primary bacteremia or respiratory tract infection and higher SOFA score were positively associated with clinical failure (adjusted odds ratio [aOR] = 2.270, 95% confidence interval [CI] = 1.115–4.620 and aOR = 1.234, 95% CI = 1.118–1.362, respectively). Receipt of CZA within 48 hours of infection onset was protective (aOR, 0.409; 95% CI, 0.180–0.930). Seventeen (8.4%) patients experienced a potential drug-related adverse effect (10 acute kidney injury, 3 Clostridioides difficile infection, 2 rash, and 1 each gastrointestinal intolerance and neutropenia) Conclusions Ceftazidime-avibactam is being used to treat a range of MDR-GN infections including Pseudomonas spp as well as CRE.

Urinary tract infections (UTIs), including catheter-associated UTIs, are among the most common bacterial infections in both inpatient and outpatient settings. Diagnosis of true UTI remains a clinical challenge, and excessive antimicrobial treatment of asymptomatic bacteriuria (ASB) or contaminated urine cultures is common. Challenges with the appropriate diagnosis of UTIs include the lack of specific signs and symptoms, no definitive diagnostic criteria, high incidence of ASB, contamination of samples, and frequent lack of indications for ordering urine cultures. Promising interventions include education and feedback, indication requirements when ordering cultures, and use of reflex culture policies that limit urine cultures. Antimicrobial and diagnostic stewardship interventions can work synergistically to decrease ordering of urine cultures without clear indication and prevent excessive antimicrobial administration in patients without clearly defined UTI.

Background Eravacycline (ERV) is Food and Drug Administration approved in patients for the treatment of adults complicated intra-abdominal infections in 2018. Real-world data regarding the indications for ERV use are is limited. We evaluated the clinical/safety outcomes of patients treated with ERV in FDA and non-FDA approved indications. Methods Multicenter, retrospective, observational study from September 2018 to June 2020. Adult patients treated with ERV for ³ 72 hours were included. The primary outcome was 30-day survival. Secondary outcomes included a lack of 30-day infection-recurrence, resolution of signs/symptoms of infection and safety. All outcomes were measured from ERV start date. Results Overall, 108 patients were included from 12 geographically-distinct medical centers across the United States. The median(IQR) age was 60(52-67) years and 60% were male. Median(IQR) APACHE II and Charlson Comorbidity scores were 15(11-21) and 3 (2-6), respectively. The most common sources of infection were intra-abdominal (32%), and respiratory (24%). Common pathogens included Acinetobacter baumannii (19%), Klebsiella pneumoniae and Enterococcus faecium (16%). Infectious diseases consultation was obtained in 98%, and surgical interventions in 51% of cases. Patients often received active therapy prior to ERV(40%). Median(IQR) ERV therapy duration was 7.7(4.4-14.0) days. Among cases with documented cultures, ERV was initiated within a median(IQR) of 4.8(2.5-9.9) days. Combination therapy ³ 48 hours was given in 45%. The primary endpoint was achieved in 79%(85/108). Of patients who died(n=23), 57% were on monotherapy, 39% were critically ill, 39% had intra-abdominal as a source, and 30% had positive blood cultures. For secondary outcomes, 94%(102/108) lacked 30-day infection-recurrence and 74%(80/108) resolved signs/symptoms of infection. ERV was selected primarily for consolidation of the regimen(40%). Eight patients experienced a probable ERV-related adverse event, mainly gastrointestinal(87.5%) and none experienced clostridium difficile. Conclusion 30-day survival was achieved in the majority of patients treated with ERV. Studies with longer follow-up are required to confirm these findings. Disclosures Madeline King, PharmD, Tetraphase (Speaker’s Bureau) Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)

Vancomycin remains the mainstay treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections, including pneumonia. There is concern regarding the emergence of vancomycin tolerance, caused by heterogeneous vancomycin-intermediate S. aureus (hVISA), and subsequent vancomycin treatment failure. Pneumonia is associated with high morbidity and mortality, especially with delays in appropriate therapy. This study evaluated the clinical outcomes of patients with hVISA pneumonia compared to those with vancomycin-susceptible S. aureus (VSSA) pneumonia. A retrospective cohort of patients with MRSA pneumonia from 2005 to 2014 was matched at a ratio of 2:1 VSSA to hVISA infections to compare patient characteristics, treatments, and outcomes. hVISA was determined by the 48-h population analysis profile area under the curve. Characteristics between VSSA and hVISA infections were compared by univariate analysis and multivariable logistic regression analysis to determine independent risk factors of inpatient mortality. Eighty-seven patients were included, representing 29 hVISA and 58 VSSA cases of pneumonia. There were no significant differences in demographics or baseline characteristics. Sequential organ failure assessment (SOFA) scores were a median of 7 (interquartile ratio [IQR], 5 to 8) in hVISA patients and 5 (IQR, 3 to 8) in VSSA ( P = 0.092) patients. Inpatient mortality was significantly higher in hVISA patients (44.8% versus 24.1%; P = 0.049). Predictors of inpatient mortality upon multivariable regression were SOFA score (adjusted odds ratio [aOR], 1.36; 95% confidence interval [CI], 1.08 to 1.70), Panton-Valentine leukocidin (PVL) positivity (aOR, 6.63; 95% CI, 1.79 to 24.64), and hVISA phenotype (aOR, 3.95; 95% CI, 1.18 to 13.21). Patients with hVISA pneumonia experienced significantly higher inpatient mortality than those with VSSA pneumonia. There is a need to consider the presence of vancomycin heteroresistance in pneumonia caused by MRSA in order to potentially improve clinical outcomes.

Background Bacteriuria associated with indwelling urinary catheters is commonly linked to inappropriate antibiotic use in hospitals. The use of external catheter devices (ECD) has increased in recent years to reduce bacteriuria risk in women, based on data in male patients. Currently no studies have shown a similar benefit in the female population. Methods This was a quasi-experimental study among adult female ICU patients with urinary catheters (indwelling or external) between 12/2015 – 5/2017 (pre-ECD) and 12/2017 – 6/2019 (post-ECD). The primary outcome was the incidence of positive urine cultures pre- vs post-intervention. An a priori subgroup patient-level analysis evaluated positive urine cultures and antibiotic use pre- vs post-intervention in medical and surgical ICU patients who had a urinalysis ordered in the presence of an indwelling or external urinary catheter. Antibiotic use was considered appropriate when prescribed in the presence of a positive urine culture, clinical signs and symptoms of UTI, and a UTI order indication. Results There were 4,640 patient ICU encounters during the study period; 2,201 pre- vs 2,439 post-intervention. Mean age was 59.2 (SD 15.4) years, median Elixhauser Score was 6 (IQR 4, 7), and there were no significant differences between groups. In the overall cohort, there was a decrease in the monthly rate of indwelling urinary catheter use pre- versus post- intervention (Figure 1) of 182/1,000 vs 166/1,000 patient days, P = 0.03. There was also a decrease in rate of positive urine cultures from pre- to post- intervention (38/1,000 vs 28/1,000 patient days, P = 0.004). Antibiotic days of therapy (DOTs) for UTI indication was similar in the pre- versus post-intervention groups with 1.9/1000 vs. 1.8 DOT/1,000 patient days (P = 0.7). In the subgroup of 210 patients (73 pre- vs 137 post-intervention) who underwent urinalysis, there was also a decrease in the proportion of positive urine cultures from pre- to post-intervention (42.5% vs. 24.3%; P = 0.007). Of patient receiving antibiotics for UTI indication, appropriateness was numerically higher post-intervention (9.1% vs. 31.6%; P = 0.21). Conclusion The use of external urinary catheters may be beneficial in reducing bacteriuria and related antibiotic use among female ICU patients. Disclosures All Authors: No reported disclosures

Background The Clinical and Laboratory Standards Institute (CLSI) revised breakpoints for cefazolin (CFZ) may be difficult to implement with current automated susceptibility testing (AST) platforms and Enterobacterales may be falsely reported as susceptible to CFZ. The possibility remains that CFZ may then be inappropriately used as definitive therapy. Methods This was a retrospective observational cohort of adult patients with Enterobacterales bloodstream infections (BSI) reported CFZ susceptible per Vitek®2 (bioMerieux, Durham NC). The primary outcome was the percentage of CFZ susceptible Enterobacterales isolates using three different susceptibility testing methods: Vitek®2 automated testing, ETEST® (bioMerieux, Durham NC), and disk diffusion. Secondary outcomes included treatment failure defined as a composite outcome of 30-day all-cause inpatient mortality, 30-day recurrent BSI, 60-day recurrent infection, or infectious complications. Results In 195 isolates reported CFZ susceptible per Vitek®2, 84 (43.1%) were CFZ susceptible using E-test vs.119 (61%) using disk diffusion (Figure 1). Rates of treatment failure were similar in both CFZ and non-CFZ groups (33.3% vs. 38.5% respectively; p=0.57). Both groups had high rates of ID consult involvement (>60%) and source control (>80%) with urinary tract being the most reported source. No difference was noted in 30-day all-cause mortality, secondary infectious complications, 30-day readmissions, or 60-day recurrent infections. A subgroup analysis of patients receiving CFZ vs. ceftriaxone suggests treatment failure was significantly less likely to occur in the setting of source control (adjusted OR 0.06; 95% CI, 0.13–0.32) and ID consult Figure 1: CFZ Susceptibilities by Testing Method Conclusion There was a large discrepancy among testing methods; additional confirmatory CFZ susceptibility testing beyond AST platforms should be considered prior to definitive use of CFZ for systemic Enterobacterales infections. Disclosures All Authors: No reported disclosures

Background Numerous number of studies have found a positive correlation between delayed appropriate antibiotic therapy and negative clinical outcomes (NCO) in Gram-negative bacterial infections (GNBI). The combination of meropenem with vaborbactam (MVB) received Food and Drug Administration approval for the treatment of complicated urinary tract infections and acute pyelonephritis caused by susceptible organisms in August 2017. We sought to determine the impact of delayed appropriate therapy with MVB on NCO among patients with GNBI. Methods Multi-center, retrospective cohort study from October 2017 to March 2020. We included adult patients treated with MVB for >72 hours. We excluded patients who received alternative appropriate antibiotics for GNB prior to MVB and patients with unknown dates for index culture. NCO were defined as 30-day mortality and/or microbiological recurrence. All outcomes were measured from MVB start date. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineates the risk of NCO. Multivariable logistic regression analysis (MLR) was used to examine the independent association between the CART-derived-BP and NCO. Variables were retained in the model if P< 0.2 and removed in a backward stepwise approach. Results A total of 86 patients were included from 13 institutions in the United States: median(IQR) age 55 (37-67) years, 67% male, and 48% Caucasian. Median(IQR) APACHE II and Charlson Comorbidity index scores were 18(11-26) and 4(2-6), respectively. Common sources of infection were respiratory (37%) and intra-abdominal (21%). The most common pathogens were carbapenem-resistant Enterobacterales (83%). CART-derived BP between early and delayed treatment was 48 hours, where NCO was increased (36% vs.7%; P=0.04). Delayed MVB initiation was independently associated with NCO in the MLR (aOR=7.4, P=0.02). Results of Regression Analysis of Variables Associated With Negative Clinical Outcomes and Delayed Appropriate Therapy with Meropenem-vaborbactam Conclusion Our results suggest that delaying appropriate antibiotic therapy with MVB for >48 hours significantly increases the risk of NCO in patients with GNBI. Clinicians must ensure timely administration of MVB to assure best outcomes in patients with GNBI. Disclosures Kevin W. Garey, PharMD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)

Background: In 2018, the Maryland Department of Health, in collaboration with the University of Maryland and Johns Hopkins University, created the Statewide Prevention and Reduction of Clostridioides difficile (SPARC) collaborative to reduce C. difficile as specified in Healthy People 2020. Methods: The SPARC collaborative recruited hospitals contributing most cases to statewide C. difficile standardized infection ratio (SIR), according to data reported to the National Healthcare Safety Network (NHSN). SPARC developed intervention bundles around 4 domains: infection prevention, environmental cleaning, and diagnostic and antimicrobial stewardship. Each facility completed a self-assessment followed by an on-site, day-long, peer-to-peer (P2P) evaluation with 8–12 SPARC subject matter experts (SMEs) representing each domain. The SMEs met with hospital executive leadership and then led 4 domain-based group discussions with relevant hospital team leaders. To identify policy and practice gaps, SMEs visited hospital inpatient units for informal interviews with frontline staff. In a closing session, SPARC SMEs, hospital executives, and team leaders reconvened to discuss preliminary findings. This included review of covert observation data (hand hygiene, personal protective equipment compliance, environmental cleaning) obtained by SPARC team 1–2 weeks prior. Final SPARC P2P written recommendations guided development of customized interventions at each hospital. SPARC provided continuous support (follow up phone calls, educational webinars, technical support, didactic training for antimicrobial stewardship pharmacists) to enhance facility-specific implementation. For every quarter, we categorized C. difficile NHSN data for each Maryland hospital into “SPARC” or “non-SPARC” based on participation status. Using negative binomial mixed models, we analyzed difference-in-difference of pre- and postincidence rate ratios (IRRs) for SPARC and non-SPARC hospitals, which allowed estimation of change attributable to SPARC participation independent of other time-varying factors. Results: Overall, 13 of 48 (27%) hospitals in Maryland participated in the intervention. The baseline SIR for all Maryland hospitals was 0.92, and the post-SPARC SIR was 0.67. The SPARC hospitals had a greater reduction in hospital-onset C. difficile incidence; 8.6 and 4.3 events per 10,000 patient days for baseline and most recent quarter, respectively. For non-SPARC hospitals, these hospital-onset C. difficile incidences were 5.1 preintervention and 4.3 postintervention. We found a statistically significant difference-in-difference between SPARC and non-SPARC hospital C. difficile reduction rates (ratio of IRR, 0.63; 95% CI, 0.44−0.89; P = .01). Conclusions: The Maryland SPARC collaborative, a public health-academic partnership, was associated with a 25% reduction in the Maryland C. difficile SIR. Hospitals participating in SPARC demonstrated significantly reduced C. difficile incidences to match that of high-performing hospitals in Maryland.Funding: NoneDisclosure: Aaron Milstone, BD – consulting.