OBJECTIVES:Oral second- and third-generation cephalosporins are increasingly used as transitional therapy for Escherichia coli bloodstream infection, particularly in patients with resistance and intolerance to first-line agents. However, many automated antimicrobial susceptibility testing (AST) systems only assess parenteral cephalosporins, potentially delaying transitions of care. Limited data exist on the correlation and surrogacy between parenteral and oral cephalosporin AST. We aimed to determine whether AST for parenteral cefazolin, ceftriaxone or cefotaxime can serve as surrogates to predict susceptibility for oral cephalosporins. METHODS:E. coli blood isolates susceptible to parenteral third-generation cephalosporins were consecutively collected from unique patients from two health systems in Phoenix, AZ, USA from January 2021 to 2023. Broth microdilution was performed according to CLSI. Categorical agreement (CA) rates were calculated using cefazolin, ceftriaxone, or cefotaxime as the surrogate antibiotic for oral cephalosporins (cefuroxime, cefaclor, cefprozil, cefdinir, cefpodoxime, cefixime). Discrepancies were classified as minor errors (mE), major errors (ME), or very major errors (VME) per CLSI. RESULTS:Among 200 isolates, susceptibility to cefazolin at MIC ≤2 mg/L, cefazolin at MIC ≤16 mg/L, ceftriaxone and cefotaxime at MIC ≤1 mg/L were 43%, 91.5% and 100%, respectively. Cefazolin MIC ≤2 mg/L provided high CA across oral cephalosporins but excessive mE (25%-37%) and ME (20%-40%) rates. Ceftriaxone and cefotaxime achieved 100% CA for oral third-generation cephalosporins with mE rates within acceptable limits; however, CA was suboptimal for oral second-generation agents (83%-88%). No surrogate antibiotic met acceptable CLSI criteria due to lack of CA, however, ceftriaxone/cefotaxime achieved acceptable limits in CA, mE, ME and VME. CONCLUSIONS:Prediction of oral second-generation cephalosporins may warrant cefazolin MIC ≤2 mg/L, despite limitations regarding false resistance and susceptibility discordant. Ceftriaxone/cefotaxime demonstrates a more reliable surrogate for predicting oral third-generation cephalosporins susceptibility. Future investigations are necessary to clinically corroborate these findings.

Carbapenemase-producing Enterobacterales (CRE) have continued to rise with high mortality. While Klebsiella pneumoniae carbapenemase (KPC) remains the most common carbapenemase, New Delhi metallo-β-lactamases (NDM) have significantly increased. Limited in vitro studies have reported CRE isolates co-producing KPC and NDM (KPC+NDM CRE); however, the impact of KPC+NDM CRE on patient outcomes remains unclear. This was a multicenter, retrospective cohort conducted at HonorHealth Network (Phoenix, AZ). Adults admitted between September 2022 and March 2025 with KPC+NDM CRE infections were included. The detection and differentiation of carbapenemases were performed with NG-Test CARBA 5 (NG Biotech, Guipry-Messac, France). The primary outcome was clinical cure at discharge. The secondary outcomes were 30-day all-cause mortality, intensive care unit (ICU) and hospital length of stay (LOS). Overall, 8 patients had confirmed KPC+NDM CRE infections with the mean age of 57 (29-82) years and mean APACHE-II score of 17 (8-30). At baseline, 6 (75.0%) patients required mechanical ventilation, 5 (62.5%) were hospitalized within the past 90 days, and 2 had CRE infection within 90 days prior to admission. The majority of patients (62.5%) were admitted from long term care facilities. K. pneumoniae was isolated in 7 (87.5%) patients, while Proteus mirabilis was isolated in 1 (12.5%) patient. Clinical cure was achieved in 7 (87.5%) patients with blood and cellulitis as the most common infection sources. Two patients with KPC+NDM CRE bacteremia were successfully managed with ceftazidime/avibactam plus aztreonam and eravacycline, respectively. The repeat blood cultures were clear within 24 hours of therapy initiation. Eravacycline was used for 1 (12.5%) intra-abdominal abscess, 1 (12.5%) cellulitis, and 1 (12.5%) osteomyelitis with the average treatment duration of 23 (7-42) days. The overall mean ICU and hospital LOS were 11(0-29) days and 22 (4-68) days. In this limited cohort of patients with KPC+NDM CRE infections, a surprisingly high rate of clinical cure was observed. Future larger, prospective studies are warranted to comprehensively characterize the clinical impacts of CRE infections harboring KPC+NDM and other combinations of carbapenemases. All Authors: No reported disclosures

Abstract Background Metallo-beta-lactamase-producing Gram-negative bacteria (MBL-GNB) has become a global healthcare threat. MBL-GNB are resistant to all first-line antimicrobials, leading to high mortality rates. Ceftazidime-avibactam plus aztreonam (CAZ-AVI+AZT) and cefiderocol (CFDC) are treatment options due to their in vitro activity against MBL-GNB. However, the optimal treatment for MBL-GNB infections remains unclear. Therefore, we sought to evaluate the outcomes of CAZ-AVI+AZT vs CFDC in patients with MBL-GNB infections. Methods Adult patients admitted to HonorHealth Network (Phoenix, AZ) from January 2018 to December 2024 who received ≥1 dose of either CAZ-AVI+AZT or CFDC with culture-confirmed MBL-GNB were included. Patients who were treated for < 48 h were excluded. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were 14-day microbiological cure, post-diagnosis intensive care unit (ICU) and hospital length of stay (LOS), and duration of therapy. Results A total of 24 patients were included, of whom 8 received CAZ-AVI+AZT and 16 received CFDC. Baseline characteristics were similar in both arms; however, CAZ-AVI+AZT patients experienced an increase in ICU admission and sepsis at baseline. Sources of infections included urine (50%), blood (42%), and respiratory tract (42%). For CAZ-AVI+AZT vs CFDC patients, all-cause in-hospital mortality occurred in 2 vs 3 patients (25% vs 19%; p = 0.72); microbiological cure occurred in 7 vs 7 patients (88% vs 44%, p = 0.11), respectively. Hospital length of stay was 9.5 ± 4 days for CAZ-AVI+AZT vs 6.5 ± 3 days for CFDC (p = 0.09). Duration of therapy and post-diagnosis ICU length of stay were similar in both groups. Conclusion CAZ-AVI+AZT compared to CFDC demonstrated no mortality benefit; however, it may achieve greater microbiological cure. Further studies are warranted to corroborate these findings. Disclosures All Authors: No reported disclosures

Abstract Background Oral second- and third-generation cephalosporins are increasingly being utilized as oral transitional therapy for Escherichia coli bloodstream infections due to resistance or intolerance to other classes. However, most automated susceptibility systems only include cefazolin (CFZ), ceftriaxone (CRO), or cefotaxime (CTX). We aimed to evaluate the susceptibility correlation of CFZ, CRO, or CTX compared to oral second- and third-generation cephalosporins to determine a potential surrogate breakpoints. Antimicrobial susceptibility and categorical agreements of intravenous and oral cephalosporins against 100 E. coli strains Methods We obtained 100 E. coli blood isolates from HonorHealth and Abrazo Health Systems in Phoenix, AZ from September 2021 to 2023. Broth microdilution was performed according to CLSI using commercially purchased CFZ, CRO, CTX, cefuroxime (CXM), cefaclor (CEC), cefprozil (CPR), cefdinir (CDR), and cefixime (CFM). E. coli ATCC 25922 was utilized as quality control. Categorical agreement and error rates were calculated for drug-drug combinations using CFZ, CRO, or CTX as the surrogate antibiotic for oral cephalosporins. Results MIC50/90 values were reported in Table 1. With the recommended CFZ surrogate breakpoint of ≤ 16 µg/mL for oral cephalosporins, the categorical agreement rates were 86% for CEC and 93% for CPR. When applying CRO and CDR breakpoint of ≤ 1 µg/mL, highest categorical agreement rates of 99% were seen with CDR, followed by those of 86% with CPR. Compared to CFZ, CRO, and CXM resulted in higher false susceptible rates with CEC and CPR. However, if CRO and CTX MIC ≤0.06 µg/mL had been used, the categorical rates would have been above 95% with CEC and CPR. CFM susceptibility could not be predicted with CFZ, CRO, or CTX due to high major error rates. Conclusion This study suggests potential utility of parenteral first- and third-generation cephalosporins as surrogates for oral counterparts within their respective second- and third- generations. Use of a lower breakpoint for third generation cephalosporins strengthens their role as surrogates. Future investigation is warranted to clinically corroborate these findings. Disclosures Kyle Molina, PharmD, Innoviva Speciality Therapeutics: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Merck: Grant/Research Support|Shionogi: Advisor/Consultant

Background Carbapenems (CAR) are first line therapy for patients with infections caused by multidrug resistant organisms. As the prevalence of antibiotic resistance is increasing, CAR use has become a common choice for empiric therapy. This increase in use is concerning as prior CAR exposure is a risk factor for CAR resistance. Identification of risk factors associated with resistance for other beta-lactam antibiotics could aid in the appropriate use of CAR therapy while minimizing overuse. The objective of this study was to identify risk factors for cefepime (FEP) and piperacillin/tazobactam (PTZ) resistance and which population required CAR as an empiric therapy. Methods This is a retrospective cohort conducted at HonorHealth John C Lincoln Medical Center, Phoenix AZ between January 2020 to July 2021. The case patients will be those who had an infection which is resistant to FEP or PTZ, while control patients have infection which is susceptible to FEP or PTZ. Recurrence of infection after receiving appropriate antimicrobial therapy considered as a separate case. Patients who do not have antimicrobial susceptibilities were excluded. Variables were compared between groups. Multivariate analysis using logistic regression was used to control for confounding variables. Results Overall, 230 patients met inclusion criteria and were evenly distributed between cohorts. The mean age of the population at baseline was 64 ± 17.4, 111 (48.3%) patients were in an ICU and 103 (44.8%) patients required mechanical ventilation. Clinical variables which were significant in univariate analysis were included in multivariate analyses. Multivariate analyses revealed prior resistance to FEP or PTZ in the past 12 months (OR 8.35, 95% CI [2.28-30.50], p=0.001), transferred from outside facility (OR 3.40, 95% CI [1.80-6.42], p< 0.001), prior ICU admission in the past 90 days (OR 4.40, 95% CI [1.72-11.27], p=0.002), and prior antibiotic use in the past 30 days (OR 2.60, 95% CI [1.33-5.09], p=0.005) were associated with increased risk of FEP- or PTZ-resistant infections. Conclusion Patients with prior resistance to FEP and PTZ within the last 12 months can benefit by initiating empiric therapy with CAR due to the increased risk for subsequent FEP- or PTZ-resistant organisms. Further investigation is warranted. Disclosures All Authors: No reported disclosures

Abstract Background Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is a significant healthcare concern in hospitalized patients with a mortality rate upward of 54%. Delayed initiation of appropriate antibiotics with MDR infections may lead to prolonged hospital stays and increased mortality. Previous studies investigated risk factors that contribute to MDR-PA and mortality; however, none evaluated factors leading to recurrence. Therefore, we sought to assess the risk factors contributing to the long-term recurrence of MDR-PA. Methods This was a retrospective case-control study of hospitalized patients at HonorHealth Network from January 2015-January 2023. Patients were included if they have ≥2 positive P. aeruginosa cultures in 1-year with MDR as first occurrence. Cases were patients with MDR-PA at second occurrence and controls were patients with no MDR-PA at the second occurrence. MDR-PA was defined as resistance to at least 1 antibiotic in ≥3 different antimicrobial classes. Risk factors associated with a secondary MDR-PA occurrence were evaluated using logistic regression backwards-stepwise analysis of clinical signs and symptoms, demographic, admission location, and number of days since the first MDR-PA occurrence. Results Of 8,140 hospitalized patients, 209 (n=132 case, n=77 control) met study entry criteria; 52% were female and 84.8% were Caucasian. Respiratory infections (OR 3.13, 95% CI 1.22-8.04), urinary tract infections (UTIs) (OR 4.51, 95% CI 1.82-11.16), intravenous antibiotic use within the past 30 days (OR 3.03, 95% CI 1.05-8.72), and a time period of 30-59 days since the initial culture positive for MDR-PA (OR 4.34, 95% CI 1.37-13.72) were associated with an increased risk of a secondary occurrence of MDR-PA within 1 year. Conclusion Our study revealed that there is an increased risk of subsequent recurrence between 30-59 days following the initial MDR-PA positive culture. However, further investigations are warranted in the future to be generalizable. Disclosures All Authors: No reported disclosures

Novel therapies for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) are needed in the setting of reduced antibiotic susceptibilities and therapeutic failure. Ceftaroline is a cephalosporin antibiotic with MRSA activity. Although not FDA approved for MRSA BSI, ceftaroline has generated much interest as a potential treatment option. However, detailed descriptions of its use in this setting remain limited. To address this, we conducted a retrospective, multicenter, observational study of adult patients with MRSA BSI treated with at least 72 h of ceftaroline from 2011 to 2015. Safety outcomes were examined in the overall cohort, while efficacy outcomes were examined among patients who had not cleared their BSI prior to ceftaroline initiation. Data were also stratified by ceftaroline monotherapy or combination therapy. Predictors of clinical failure on ceftaroline treatment were also sought. Overall, 211 patients were included in the safety population; Clostridium difficile infection, rash, and neutropenia occurred in 6 patients (2.8%), 7 patients (3.3%), and 3 patients (1.4%), respectively. Clinical success was observed in 86 (68.3%) of the 126 patients included in the efficacy population. The monotherapy and combination therapy subgroups had similar proportions of patients experiencing success (69.7 and 64.9%, respectively). The median BSI durations post-ceftaroline treatment were 2 days (interquartile range, 1 to 4 days) for monotherapy and 3 days (interquartile range, 1.5 to 5 days) for combination therapy. Higher acute physiology and chronic health evaluation II scores and comorbid malignancy independently predicted treatment failure. Ceftaroline appears effective for MRSA BSI as both monotherapy and combination therapy. However, comparative studies are needed to further delineate the role of ceftaroline in MRSA BSI treatment.

Penicillin plus ceftriaxone is a promising alternative to ampicillin plus ceftriaxone for the treatment of Enterococcus faecalis infective endocarditis. Limited data is available supporting the utilization of penicillin plus ceftriaxone. A total of 20 E. faecalis isolates; one wild-type strain (JH2-2) and 19 clinical blood strains were assessed for penicillin plus ceftriaxone and ampicillin plus ceftriaxone synergy using a 24-h time-kill experiment. Susceptibility was determined by broth microdilution. Differences in bactericidal, bacteriostatic, or inactivity, as well as synergy between treatments were assessed by chi-square or Fisher exact test. All E. faecalis isolates were considered susceptible to ampicillin and penicillin. Ampicillin plus ceftriaxone versus penicillin plus ceftriaxone similarly demonstrated synergy. Bactericidal activity was more commonly observed for ampicillin plus ceftriaxone versus penicillin plus ceftriaxone. Among isolates with a penicillin MIC of 4 mu g/ mL (n = 7), synergistic activity for both combinations was less common compared to isolates with a penicillin MIC <= 2 mg/ mL (n = 13). Ampicillin plus ceftriaxone and penicillin plus ceftriaxone demonstrate similar synergistic potential against E. faecalis clinical blood isolates, but strains with higher penicillin and ceftriaxone MICs less frequently demonstrated synergy. Further research is warranted to determine the role of the penicillin plus ceftriaxone therapy and the penicillin MIC in clinical practice. IMPORTANCE Penicillin plus ceftriaxone demonstrates similar synergistic activity against Enterococcus faecalis to ampicillin plus ceftriaxone. Isolates with a penicillin MIC of 4 mg/L and a ceftriaxone MIC of 512 or higher, lack penicillin plus ceftriaxone synergy despite the penicillin susceptibility MIC breakpoint of 8 mg/L.

Abstract Background Staphylococcus aureus prosthetic valve infective endocarditis (SA-PVIE) is associated with high mortality. Gentamicin (GEN) with anti-staphylococcal antibiotics and rifampin are guideline recommendations for SA-PVIE extrapolated from in vitro data. GEN can lead to acute kidney injury (AKI), meanwhile, the clinical benefit on infection-related outcomes remains unclear. Therefore, we evaluated the impact of GEN on outcomes in SA-PVIE. Methods This is a multicenter, retrospective cohort conducted at HonorHealth and UCHealth systems. Adults admitted between January 2014-2022 with definite/possible SA-PVIE by Duke Criteria were included if they received ≥2 days of treatment within 2 days of index culture. Cohorts were stratified by GEN receipt. The primary outcome was 90-day all-cause mortality. The secondary outcomes were treatment failure (change in antimicrobials, abscess development, new indication for cardiac surgery), 30-day all-cause mortality, and incidence of AKI by KDIGO Criteria. Results Overall, 38 patients with definite (40%) and possible SA-PVIE (60%) met inclusion (13 GEN, 25 without GEN [no-GEN]). At baseline, 15 (40%) patients were in an ICU, median Pitt bacteremia score was 2, and methicillin-susceptible S. aureus predominated (71%). A total of 10 (26%) patients had valve surgery; median bacteremia duration was similar between GEN and no-GEN (4 vs 3 days, p = 0.26). Common antibiotics were vancomycin (95%), cefazolin (63%), and nafcillin (21%); rifampin was more common in GEN than no-GEN (20% vs 77%, p < 0.001). Baseline AKI (44% vs 46%) and renal impairment (8% vs 0%) were not different between GEN and no-GEN, respectively. GEN was initiated a median 3 days after index culture, most commonly as intermittent strategy (69%) with 3 mg/kg daily equivalent (84.6%). There was no statistical difference in treatment failure (23% vs 24%, p=0.17), 30-day mortality (20% vs 39%, p=0.22), or 90-day mortality (28% vs 43%, p=0.263) between GEN and no-GEN, respectively. Three in the (23%) GEN group experienced AKI, compared to 10 (40%) in no-GEN. Conclusion We did not find that the addition of GEN to SA-PVIE therapy enhanced mortality benefit, yet patients without GEN may live to experience adverse events. Further studies were warranted. Disclosures All Authors: No reported disclosures.

Abstract Background Carbapenem resistance is a major concern of the World Health Organization (WHO) and Centers for Disease Control (CDC). The mortality in carbapenem-resistant infection ranges from 26-44%. Delays in appropriate antibiotic therapy can lead to increased mortality and longer hospital stay. Studies have identified several risk factors associated with carbapenem resistance including mechanical ventilation, indwelling devices, recent invasive surgery, severity of illness, recent hospitalization, and prior antibiotic exposure. However, most of these studies include Enterobacterales and not Acinetobacter baumannii or Psuedomonas aeruginosa. Therefore, we aimed to identify risk factors associated with carbapenem resistance to all pathogen types and develop a risk scoring tool. Methods This was an observational nested case-control study of hospitalized patients from January 2016-2022. Risk factors were compared for patients with culture-confirmed carbapenem-resistant gram-negative (GN) organisms (CRO) vs culture-confirmed carbapenem-susceptible GN organisms (CSO). Using accumulated data and logistic regression backwards-stepwise analysis, a scoring tool was created with c-statistic validation performed on a 75% subsample. Results There were 1,020 CRO and 51,157 CSO patients identified. Patients were primarily female (70.6%) with a mean age of 61 years. The most common CRO site of infection was respiratory (47.1%) followed by urine (29.0%). CRO pathogens included Pseudomonas (66.6%), Acinetobacter (18.9%), and Enterobacterales (14.5%). Included risk factors in the final tool were age 46-79 years, male sex, prior admission, prior invasive procedure, prior antibiotic use, admission unit, APACHE II score, chronic diseases (cardiovascular, liver, renal, respiratory), infection site, and nosocomial infection (c-statistic, 0.879). A separate scoring tool was created to include pathogen type, once identified, improving the accuracy of the scoring tool (c-statistic, 0.941). Conclusion Utilizing obtainable risk factors, a straightforward scoring tool can be used to predict carbapenem resistance to, provide guidance for treatment decisions. Further validation of scoring tool is warranted. Disclosures All Authors: No reported disclosures.

Abstract Background Pulmonary fibrosis (PF) is a well-known consequence of severe lung disease and is associated with permanent changes as well as irreversible pulmonary dysfunction. The development of PF in patients infected with COVID-19 has been documented in multiple studies and case reports. However, prevalence and outcomes associated with PF have not been well established. Therefore, we sought to evaluate the prevalence and clinical outcomes of PF among patients infected with COVID-19. Methods This is an observational cohort study from January 2020 – January 2022. We collected data from adult patients diagnosed with COVID-19 who had at least two separate computerized tomography (CT) scans. Patients were grouped based on whether evidence of developing PF, defined by clinical radiological parameters, were seen on CT. The initial CT must be negative for PF to be included. We collected the following information: baseline characteristics, secondary infection, mortality, and treatments. The primary objective was to determine the prevalence of PF among COVID-19 patients. Secondary objectives were to evaluate the differences in 30-day all-cause mortality; intensive care unit (ICU) mortality; and prevalence of secondary infections. Results A total 161 patients were COVID-19 positive with multiple CT scans; 27 (16.8%) had signs of PF while 134 (83.2%) did not. Of the patients with signs of PF, 13 (48.1%) were male (mean age of 57 years) and 13 (48.1%) were admitted to the ICU. There was no difference in secondary bacterial infection between fibrotic and non-fibrotic patients (55.6% vs 38.5%, p=0.20). The most common bacterial infection among PF patients was caused by S. aureus (26.7%). The most common infection type among PF patients was nosocomial pneumonia (46.7%). Mortality at 30-day was higher in the fibrotic patients, 70% vs 24.2% (p< 0.01). The ICU mortality trended higher in the fibrotic group (69.2% vs 36.6%, p=0.124), although it was not statistically significant. Conclusion Pulmonary fibrosis can be fatal as a complication of COVID-19. Further investigation is warranted to evaluate the outcomes of PF in patients with COVID-19. Disclosures All Authors: No reported disclosures.

Abstract Background Synergistic ampicillin plus ceftriaxone (AC) for Enterococcus faecalis infective endocarditis outpatient use is precluded by ampicillin’s poor room temperature stability. Penicillin has superior stability and has been combined with ceftriaxone (PC), however there is a lack of studies to demonstrate synergy. Methods AC and PC were evaluated, in duplicate, for synergy utilizing 24-hour in vitro time-kill assays with a starting inoculum of 106 colony forming units (CFU)/mL. Six clinical E. faecalis blood isolates and one wild-type E. faecalis isolate (JH2-2) were included. All isolates were susceptible to ampicillin and penicillin, with minimum inhibitory concentrations (MICs) ranging from 0.5-1 µg/mL and 2-4 µg/mL, respectively. Ampicillin and penicillin were tested at subinhibitory concentrations (0.25x and 0.5xMIC) as monotherapy and in combination with ceftriaxone average steady state concentrations for a dose of 2g IV q12hr (CPss 17.2 µg/mL), as all ceftriaxone MICs were high due to intrinsic resistance (MICs 128-2048 µg/mL). Synergy was defined as a ≥ 2 log10 decrease in CFU/mL at 24 hours from the most active single agent. Results An average increase in bacterial density from the starting inoculum was observed for all isolates against ampicillin 0.25xMIC alone, penicillin 0.25x and 0.5xMIC alone, and ceftriaxone alone (+1.60 ± 0.62, +1.91 ± 0.37, +1.48 ± 0.42, and +1.84 ± 0.46 log10 CFU/mL, respectively) [Table 1]. Ampicillin 0.5xMIC alone average increase in bacterial density from starting inoculum for all but two isolates (e2008 and e2009) was +1.21 ± 0.59 log10 CFU/mL. Isolates e2008 and e2009 were the only isolates with a higher penicillin MIC of 4 µg/mL, and did not display synergy for all AC and all PC combinations. AC synergy was observed for all other isolates, with only one isolate (e2012) displaying synergy at 0.5xMIC. PC synergy was observed for four isolates at 0.5xMIC (-3.47 ± 0.94 log10 CFU/mL) and for only one isolate (e2014) at 0.25xMIC but the change in bacterial density was -0.38 ± 0.24 log10 CFU/mL. Conclusion PC synergy against E. faecalis was observed with higher penicillin concentrations. AC and PC did not demonstrate synergy against isolates with a higher penicillin MIC of 4 µg/mL. Further research is warranted to better understand PC synergy against E. faecalis. Disclosures All Authors: No reported disclosures

Abstract 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.

Background: Vancomycin therapeutic drug monitoring is routinely performed but the specific measure used in practice is variable. Objective: To evaluate the relationship between the first measured vancomycin trough, area-under-the-curve (AUC), and failure in patients with MRSA bacteremia. Methods: This retrospective, cohort study included adult non-neutropenic patients with MRSA bacteremia who received vancomycin. The primary outcome was treatment failure. Initial trough and AUC values were compared between the failure and success groups. Classification and regression tree analysis was used to identify thresholds associated with failure. Multivariate analysis was performed to control for identified confounders. Results: There were 89 patients. Failure occurred in 23 (26%). Trough and AUC values associated with failure were < 10.6 mg/L (39% vs. 13%; P = 0.006) and AUC < 410mg*h/L (40% vs. 17%; P = 0.014). Both remained significant after controlling covariates (trough < 10.6 mg/L, OR [95% CI] = 4.91 [1.6-15]; AUC<410mg*h/L, OR [95% CI] = 3.13 [1.14-8.62]). Only AUC was predictive of nephrotoxicity. Conclusion: Failure was more common with troughs < 10.6 mg/L or AUC < 410 mg*h/L. Supratherapeutic AUCs, but not trough, were associated with nephrotoxicity. (c) 2021 Elsevier Inc. All rights reserved.

Abstract Background Treatment of intraabdominal infections (IAI) commonly involves broad spectrum antimicrobials based on the severity and etiology of infections as well as the underlying medical conditions. However, the overuse of broad-spectrum agents has driven selection for Gram-negative and -positive resistance, as well as collateral consequences such as Clostridioides difficile colitis. We sought to evaluate the utilization of a pharmacy-driven multifaceted antimicrobial stewardship (AMS) intervention to optimize empiric antimicrobial therapy by risk stratification among IAI patients and reduce the number of antibiotic treatment days. Methods This is a single-center case observation study in hospitalized adult IAI patients on antimicrobial therapy from Dec 2019-Feb 2020 compared to patients from Dec 2020-Feb 2021 after initiation of AMS with daily prospective audit and feedback. The composite primary outcome is reduction of antibiotic treatment days and de-escalation from broad spectrum antibiotics (fluoroquinolones, piperacillin/tazobactam, and carbapenems) to cephalosporins. Results We identified 40 patients each in the baseline (pre-AMS group) and post-AMS group via electronic medical record. Baseline characteristics were well-matched between groups. The majority of patients were diagnosed with community-acquired IAIs such as appendicitis, diverticulitis, and cholecystitis. Fluoroquinolone use as empiric therapy was significantly lower in the post-AMS group vs. pre-AMS group (2.5% vs. 25%, p< 0.001), while non-Pseudomonas cephalosporin use was increased (25% post-AMS vs. 0% pre-AMS, p< 0.001). Oral fluoroquinolone use at discharge was significantly decreased in the post-AMS group (p< 0.001). Antibiotic treatment days remained unchanged. There was no statistical difference between the two groups in 30-day mortality, 30-day readmission, relapse, and C. difficile colitis. Conclusion A multifaceted antimicrobial therapy intervention successfully reduced the use of fluoroquinolones in patients with community-acquired IAI during hospitalization and discharge. No differences in mortality, readmission, or relapse rates were observed. Disclosures All Authors: No reported disclosures

Abstract Background Treatment of asymptomatic bacteriuria (ASB) and asymptomatic candiduria (ASC) is a leading cause of inappropriate use of antimicrobial therapy in many healthcare facility, and has been associated with undesirable outcomes such as Clostridium difficile infection, longer length of stay, long-term antibiotic resistance, and delayed time back to baseline activity. This evaluation was designed to utilize a pharmacy-driven multifaceted antimicrobial stewardship intervention to reduce the number of antibiotic treatment days in patients with ASB/ASC Methods This retrospective single-center study included hospitalized adult patients with a positive urinalysis and/or a positive urine culture with or without antimicrobial therapy from January-March 2019, compared to patients from January-March 2020 after initiation of a multifaceted antimicrobial stewardship intervention, including daily prospective audit and feedback. The primary outcome was the number of antibiotic treatment days in patients with ASB/ASC before and after implementation of the targeted antimicrobial stewardship interventions Results 189 patients were identified upon retrospective chart review in the pre-group and 110 patients were included in the post-group. Baseline characteristics were well-matched between groups, except that the pre-group had a higher percentage of patients coming from nursing facilities while the post-group had a significantly higher percentage of patients with positive urine cultures. Antibiotic treatment days were significantly lower in the post- versus pre-group 0 (IQR 0–3) vs. 3 (IQR 1–7), p< 0.001. Incidence of ASB/ASC treatment was also significantly lower in the post- versus pre-group 45.5 vs 72.5%, p< 0.001. There was no statistical difference between the two groups in 30-day mortality, 30-day hospital readmission, and hospital length of stay. There was one case of Clostridium difficile infection among patients being inappropriately managed with antibiotics in each groups Conclusion A multifaceted antimicrobial stewardship interventions successfully reduced antimicrobial treatment days in patients with ASB/ASC, as well as overall incidence of inappropriate treatment of ASB/ASC without increasing mortality or readmission rate Disclosures All Authors: No reported disclosures

Background: The Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) scoring system is a validated system to predict augmented renal clearance in trauma patients. This study examined the ability of the ARCTIC score to identify patients at risk for subtherapeutic vancomycin trough concentrations relative to estimated creatinine clearance (eCrCl) alone. Methods: Trauma patients admitted to the intensive care unit from September 2012 to December 2017 who received vancomycin and had a vancomycin trough concentration recorded were included. Patients were excluded if their serum creatinine concentration was >1.3 mg/dL, if they had received vancomycin doses <30 mg/kg per day, an improperly timed trough concentration measurement, or renal replacement therapy. The primary endpoint was an initial subtherapeutic vancomycin trough concentration (<10 mg/L). Classification and regression tree (CART) analysis was used to identify thresholds for the ARCTIC score and other continuous data where subtherapeutic troughs were more common. A step-wise logistic regression analysis was performed to control for confounders for subtherapeutic troughs whereby inclusion of ARCTIC was modeled sequentially after eCrCl. Results: A total of 119 patients with a mean age of 42 +/- 17 years and eCrCl 142 +/- 39 mL/min met the inclusion criteria. The mean daily vancomycin dose was 44 +/- 9 mg/kg, and the incidence of subtherapeutic trough concentration was 46%. The CART analysis identified two variables creating three groups where subtherapeutic trough concentrations differed: eCrCl >105 mL/min and ARCTIC score >= 7, eCrCl >105 mL/min and ARCTIC score <7, and eCrCl <= 105 mL/min. The base logistic regression model identified eCrCl >105 mL/min and pelvic fracture as risk factors for subtherapeutic trough values. The final model included the addition of ARCTIC score >= 7, which improved the model significantly (p = 0.009). Predictors of subtherapeutic trough concentrations were (odds ratio [95% confidence interval]): eCrCl >105 mL/min (6.5 [1.66-25.07]), ARCTIC score >= 7 (3.26 [1.31-8.09]), and pelvic fracture (4.36 [1.27-14.93]). Conclusion: The ARCTIC score is useful when applied in conjunction with eCrCl. Patients with a eCrCl >105 mL/min and an ARCTIC score >= 7 may require a more aggressive dosing strategy.