Uncomplicated Bacteremia Research Articles

Use of Fluoroquinolones or Sulfamethoxazole-Trimethoprim Compared to Β-Lactams for Oral Step-Down Therapy in Hospitalized Patients With Uncomplicated Enterobacterales Bacteremia.

Antibiotic therapy for uncomplicated Enterobacterales bacteremia from a urinary source has traditionally consisted of fluoroquinolones (FQs) and sulfamethoxazole-trimethoprim (SXT). However, adverse events associated with FQs and emerging antimicrobial resistance have led to alternative agents, specifically oral Β-lactams (OBLs), being utilized despite concern of subtherapeutic serum concentrations related to their low relative bioavailability. To compare efficacy of antibiotic therapies with bioavailability differences in patients with uncomplicated bacteremia from a urinary source. This was a retrospective study comparing clinical efficacy in hospitalized adult patients receiving OBL or FQ/SXT. Patients were required to receive at least 48 hours of appropriate intravenous antibiotic therapy and at least one dose of oral therapy. The primary outcome was all-cause hospital readmission within 30 days of discharge. Secondary outcomes included readmission with recurrent infectious etiology and readmission due to Clostridioides difficile infection. Of 210 eligible patients, 91 received FQ/SXT and 119 received OBL. There was no difference between the groups in all-cause hospital readmission (FQ/SXT: 16.5%; OBL: 14.3%) (P = 0.660 [95% confidence interval, CI = -0.076, 0.120]) or readmission with recurrent bacteremia (FQ/SXT: 0%; OBL: 3.4%) (P = 0.135). There was a significant difference in repeat hospital admission with recurrent urinary tract infection (UTI) (FQ/SXT: 0%, OBL: 5.0%) (P = 0.037). OBLs appear to be non-inferior to FQ/SXT in the rate of all-cause hospital readmission within 30 days. However, OBLs may be associated with increased readmissions with recurrent UTI.

Is shorter always better? The pros and cons of treating Gram-negative bloodstream infections with 7 days of antibiotics.

Accumulating evidence from randomized controlled trials (RCTs) supports 7 days treatment for uncomplicated Gram-negative bacteraemia. However, some patient populations were not well represented in these RCTs, including critically ill patients, immunocompromised patients and those with MDR bacteria. In this debate document, we discuss the pros and cons for treating patients with Gram-negative bacteraemia with a 7 day antibiotic course. We surmise that the patients who were not well represented in the RCTs are probably those who have most to lose from the drawbacks of prolonged antibiotic courses, including adverse events, superinfections and resistance development. Treatment durations among these patients can be managed individually, with C-reactive protein or procalcitonin guidance or by clinical measures, and with care to discontinue antibiotics as soon as the patient recovers clinically from the infection.

Protocolo para el manejo de las infecciones graves por Staphylococcus aureus

Staphylococcus aureus (SA) infections are common and have a high morbidity and mortality. The main antibiotics for treating methicillin-sensitive SA (MSSA) are cloxacillin and cefazolin. The main drugs for treating methicillin-resistant SA (MRSA) are vancomycin and daptomycin. Other antibiotics that may be of use include linezolid, rifampicin, or fluoroquinolones. In the empirical treatment of SA infections, the risk of MRSA must be taken into account. The treatment target and its duration, in absence of bacteremia, is conditioned in large part by the source of the infection and whether it is suitably controlled or not. When bacteremia is present, the possibility of infectious endocarditis must be evaluated and follow-up blood cultures must be conducted until they are negative. For uncomplicated bacteremia, 14 days of treatment from the first negative blood culture are necessary whereas if the bacteremia is complicated, treatment must have a duration of at least 28 days.

Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection

BackgroundThe key virulence factors responsible for hypervirulent Klebsiella pneumoniae (hvKp) infection remains elusive.MethodsWe analyzed K. pneumoniae isolates collected between 2017 and 2019 and defined hvKp as a pyogenic infection. Classical K. pneumoniae (cKp) involved a non-invasive infection or uncomplicated bacteremia. Isolates belonging to the K. pneumoniae species complex were excluded.ResultsWe analyzed 112 isolates, including 19 hvKp, 67 cKp, and 26 colonizers, using whole-genome sequencing. Population genomics revealed that the K1-sequence type (ST) 82 (O1v1) clade was distinct from that of the K1-ST23 (O1v2) clone. The virulence gene profiles also differed between K1-ST82 (aerobactin and rmpA) and K1-ST23 (aerobactin, yersiniabactin, salmochelin, colibactin, and rmpA/rmpA2). The K2 genotype was more diverse than that of K1. A neighboring subclade of K1-ST23 (comprising ST29, ST412, ST36, and ST268) showed multidrug resistance and hypervirulence potentials. Logistic-regression analysis revealed that diabetes mellitus was associated with K. pneumoniae infection (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 1.14–14.8). No significant association was found between hvKp diagnosis and clinical characteristics, such as diabetes mellitus or community acquisition. However, the K1 genotype (OR: 9.02; 95% CI: 2.49–32.7; positive-likelihood ratio [LR]: 4.08), rmpA (OR: 8.26; 95% CI: 1.77–38.5; positive LR: 5.83), and aerobactin (OR: 4.59; 95% CI: 1.22–17.2; positive LR: 3.49) were substantial diagnostic predictors of hvKp.ConclusionsThe K1 genotype, rmpA, and aerobactin are prominent predictors of hvKp, suggesting that further pyogenic (metastatic) infection should be examined clinically. These findings may shed light on key hvKp virulence factors.

180. Duration of Therapy and Clinical Outcomes in Adult Oncology Patients with Uncomplicated Coagulase Negative Staphylococcal Bacteremia

BackgroundAlthough they are often considered contaminants, coagulase negative staphylococci (CoNS) can be pathogens especially in immunocompromised patients. National and local guidelines recommend treatment durations of 7 to 14 days, depending on specific clinical scenarios. The objective was to characterize the duration of treatment for CoNS bacteremia and clinical outcomes at our cancer center. MethodsWe conducted a retrospective chart review of adult patients ≥18 years old with ≥1 blood culture with growth of CoNS between 1/1/17 and 12/31/19 at our cancer center. Patients with complicated CoNS bacteremia and polymicrobial infections were excluded.ResultsAmong 128 patients identified during the study period, 98 met inclusion criteria (Figure 1). Most patients (N= 92; 94%) had a hematologic malignancy as the underlying oncologic diagnosis, and 68 (69%) were hematopoietic stem cell transplant recipients. The median total antibiotic duration was 13 days, and median duration from the date of 1st negative blood culture was 12 days; 29 (30%) patients were treated for a total duration of >14 days (Figure 2). The catheter was retained in 67 (68%) and exchanged in 4 (4%) of the cases. Three (3%) patients had recurrence of bacteremia within 30 days of treatment completion, and 8 (8%) patients were transferred to the ICU within 7 days of the index blood culture. The 30-day crude mortality rate was 10%. The most commonly used antibiotic for treatment was vancomycin (N= 95; 97%), and 32 (34%) patients on vancomycin had an increase in serum creatinine of ≥ 50% from baseline. Five (5%) patients discontinued vancomycin due to nephrotoxicity, and 4 (4%) patients required hemodialysis.Figure 1. Results Overview Among 128 patients identified during the study period, 98 met inclusion criteria. Of those included, 36 had one set of blood cultures that were positive for CoNS and 62 patients had at least two sets of blood cultures that were positive for CoNS.Figure 2. Duration of Antibiotic Treatment We evaluated duration of treatment based on total antibiotic duration and duration from date of 1st negative blood culture. The number of patients is noted above each bar.ConclusionAlthough the majority of patients were treated for ≤14 days for uncomplicated CoNS bacteremia, nearly 1/3 of patients were treated for > 14 days. Recurrent bacteremia was uncommon despite catheter retention in most patients. Relatively high rates of vancomycin associated nephrotoxicity highlight opportunities for antimicrobial stewardship to limit duration of vancomycin therapy among cancer patients with uncomplicated CoNS bacteremia. Disclosures All Authors: No reported disclosures

1126. Short-Course Therapy and Transition to Enteral Antibiotics for Uncomplicated Bacteremia Due to Enterobacterales Species

Abstract Background Gram-negative bacteremia historically has been treated with 10-14 days of parenteral antibiotics. However, data supporting this practice are lacking, and recent evidence shows equivalent outcomes for short-course (SC) therapy (7 days) and early (by day 5) conversion to highly bioavailable enteral (PO) antibiotics for Enterobacterales bacteremia. Methods Under a QI framework, we used PDSA cycles to reduce treatment duration and increase use of PO levofloxacin or trimethoprim-sulfamethoxazole for uncomplicated Enterobacterales bacteremia among Infectious Diseases (ID) clinicians at a children’s hospital in Boston, MA. We conducted an education session on evidence to support these practices for ID faculty and fellows in October 2020. In December 2020, we implemented standardized recommendations for a 7-day duration and early PO transition for eligible patients (≥ 3-months-old, ≤ 2 days monomicrobial bacteremia, with source control and return to baseline clinical status) that could be inserted automatically into electronic consult notes. In February 2021, we reinforced this practice to ID providers. We collected data before and after these interventions on ID recommendations and on patients’ actual antibiotic management. Results From 11/01/20 to 05/31/21, mean recommended treatment decreased from 10.6 to 9.5 days; however, mean duration received was similar (11.2 vs 11.7 days) (Figure 1). The percentage of patients for whom ID recommended PO conversion and in whom transition to PO agents by day 5 occurred increased from 27% to 37.5%. Figure 1. Change in average duration of antibiotics recommended and received, in days Conclusion Education and creation of automated standardized recommendations led to decreased recommended treatment durations and increased PO conversions for Enterobacterales bacteremia, but only modestly. This quality improvement initiative demonstrates the potential benefits of education and electronic documentation tools to facilitate evidence-based practice changes, but also highlights the difficulty in changing practice even amongst ID clinicians. Further PDSA cycles will be targeted at increasing more consistent awareness among a large ID division in addition to other stakeholders. Disclosures Gabriella S. Lamb, MD, MPH, Nothing to disclose

657. Genomic Insights into Virulence Factors Affecting a Tissue-invasive Klebsiella pneumoniae Infection

BackgroundJapan is one of the hypervirulent Klebsiella pneumoniae (hvKp) endemic areas, resulting in an alarming issue in actual clinical settings. However, little is known regarding key virulence factors responsible for hvKp infection.MethodsWe analyzed K. pneumoniae isolates collected between 2017 and 2019, and defined hvKp as a pyogenic infection. Classical K. pneumoniae (cKp) involved a non-invasive infection or uncomplicated bacteremia. Isolates belonging to the K. pneumoniae species complex were excluded.ResultsWe analyzed 112 isolates, including 19 hvKp, 67 cKp, and 26 colonizers, by whole-genome sequencing. Population genomics revealed that the K1-sequence type (ST) 82 clade was distinct from that of K1-ST23 clone (Figure 1). The virulence-gene profiles also differed between K1-ST82 (aerobactin and rmpA) and K1-ST23 (aerobactin, yersiniabactin, salmochelin, colibactin, and rmpA/rmpA2). The K2 genotype was more diverse than that of K1. A neighboring subclade of K1-ST23 (comprising ST29, ST412, ST36, and ST268) showed multidrug-resistance and hypervirulence potentials. Logistic-regression analysis revealed that diabetes mellitus was associated with K. pneumoniae infection (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 1.14–14.8). No significant association was found between hvKp diagnosis and clinical characteristics, such as diabetes mellitus or community acquisition (Table 1). The K1 genotype (OR: 9.02; 95% CI: 2.49–32.7; positive-likelihood ratio [LR]: 4.08), rmpA (OR: 8.26; 95% CI: 1.77–38.5; positive LR: 5.83), and aerobactin (OR: 4.59; 95% CI: 1.22–17.2; positive LR: 3.49) were substantial diagnostic predictors of hvKp (Table 2).Figure 1. Phylogenetic distribution of genetic virulence factors in 112 K. pneumoniae isolates The highlighted strains are clinically pathogenic (orange, hypervirulent K. pneumoniae; yellow, classical K. pneumoniae; sky blue, colonization). The non-highlighted strain (NTUH-K2044) is a reference K. pneumoniae strain. ConclusionIn hvKp-rich settings, diabetes mellitus, community-acquisition, and siderophores other than aerobactin were not remarkable predictors of hvKp infection. However, the K1 genotype, rmpA, and aerobactin were found to be substantial predictors, warranting clinical assessment of any possible/further pyogenic (metastatic) infection. We believe that these findings shed light on key hvKp virulence factors.Disclosures All Authors: No reported disclosures

219. Outcomes with Low- vs. High-bioavailability Oral Antibiotics in Treatment of Uncomplicated Gram-Negative Bacteremia

BackgroundHigh-bioavailability (HIGH-BIO) oral agents (i.e. trimethoprim-sulfamethoxazole, fluoroquinolones) are increasingly utilized for definitive treatment of uncomplicated gram-negative (UGN) bloodstream infections (BSI). Literature supports use of HIGH-BIO agents as step-down therapy, but few studies have assessed use of low-bioavailability (LOW-BIO) agents (i.e. beta-lactams). Increased recurrence of BSI has been associated with LOW-BIO agents; suboptimal dosing of beta-lactam agents may have impacted outcomes. Trials have not assessed whether high-dose beta-lactams (HD-BL) improve clinical outcomes over low-dose beta-lactams (LD-BL) for UGN BSI.MethodsThis retrospective cohort study conducted between December 2016 and December 2020 included adults with UGN BSI administered oral step-down therapy for at least 1/3rd the total antibiotic duration. The primary outcome was incidence of treatment failure of HIGH-BIO compared to LOW-BIO agents within 90 days of completing oral therapy. Treatment failure was a composite of all-cause mortality, recurrent BSI, reinfection of the primary site, or transition to IV antibiotics after initiating oral therapy. Secondary outcomes were incidence of treatment failure of HIGH-BIO compared to HD-BL agents, and of HD-BL compared to LD-BL agents.ResultsOf 225 patients, 67 (29.8%) received a HIGH-BIO and 158 (70.2%) a LOW-BIO agent; of those in the LOW-BIO arm 126 (79.7%) received a HD-BL. The most common source of BSI was urinary (202 [89.8%]); transition to oral therapy occurred after a mean of 5 ± 2.39 days. No difference in treatment failure was observed (8 [11.9%] HIGH-BIO vs. 25 [15.8%] LOW-BIO, P = 0.45). A numerically higher number of patients in the LOW-BIO arm had recurrent BSI (4 [2.5%] LOW-BIO vs. 0 [0%] HIGH-BIO, P = 0.18). No difference in treatment failure was observed between HIGH-BIO and HD-BL agents (8 [11.9%] vs. 20 [15.9%], P = 0.46), or HD-BL and LD-BL agents (20 [15.9%] vs. 5 [15.6%], P = 0.97). ConclusionNo difference in treatment failure was observed between groups; further study is needed due to failure to reach statistical power. A numerical trend towards increased recurrence of BSI was observed with LOW-BIO agents. Beta-lactams may be reasonable for step-down therapy of UGN BSI if HIGH-BIO agents are contraindicated. Disclosures All Authors: No reported disclosures

Complicated Streptococcus agalactiae Sepsis with/without Meningitis in Young Infants and Newborns: The Clinical and Molecular Characteristics and Outcomes.

Background: Streptococcus agalactiae (also known as group B streptococcus, GBS) is associated with high mortality and morbidity rates in infants, especially those with complicated GBS sepsis, defined as those with meningitis, severe sepsis and/or septic shock. We aimed to characterize the clinical and molecular characteristics and risk factors for adverse outcomes of neonates with invasive GBS diseases. Methods: From 2003 to 2020, all neonates with invasive GBS diseases who were hospitalized in a tertiary-level neonatal intensive care unit (NICU) were enrolled. The GBS isolates underwent serotyping, multilocus sequence typing (MLST) and antibiotic susceptibility testing. We compared cases of complicated GBS sepsis with uncomplicated GBS bacteremia. Results: During the study period, a total of 188 neonates (aged less than 6 months old) with invasive GBS diseases were identified and enrolled. Among them, 119 (63.3%) had uncomplicated GBS bacteremia and 69 (36.7%) neonates had complicated GBS sepsis, including meningitis (25.5%, n = 48) and severe sepsis or septic shock. Among neonates with complicated GBS sepsis, 45 (65.2%) had neurological complications, and 21 (42.0%) of 50 survivors had neurological sequelae at discharge. The overall final mortality rate was 10.1% (19 neonates died). Type III/ST-17 GBS isolates accounted for 56.5% of all complicated GBS sepsis and 68.8% of all GBS meningitis, but this strain was not significantly associated with worse outcomes. The antimicrobial resistance rate among the invasive GBS isolates was obviously increasing in the past two decades. After multivariate logistic regression analysis, neonates with thrombocytopenia and respiratory failure were independently associated with final adverse outcomes. Conclusions: a total of 36.7% of all neonatal invasive GBS diseases were associated with complicated sepsis with/without meningitis. Given the high mortality and morbidity rates in neonates with complicated GBS sepsis, further studies for early identification of specific strains, risk factors or genetic mechanisms that will cause complicated GBS sepsis are urgently needed in the future.

Impact of a Pharmacist-Led Antimicrobial Stewardship Program on the Number of Days of Antimicrobial Therapy for Uncomplicated Gram-Negative Bacteremia in a Community Hospital.

IntroductionThe need for pharmacist-led antimicrobial stewardship programs (ASP) is increasing.ObjectiveWe performed a retrospective study to assess whether pharmacist-led ASPs can decrease the duration of treatment for uncomplicated gram-negative bacteremia among patients admitted in a community hospital.MethodsThis research was conducted at a 325-bed regional general hospital in Japan, from January 2013 to June 2015. There are no infectious diseases specialists affiliated with the hospital. The outcomes of the pharmacist-led ASP group, who received pharmacist intervention, and the control group, who did not receive pharmacist intervention, were compared. The study included patients aged 18 years or older who were diagnosed with gram-negative bacteremia. The pharmacist performed an antimicrobial time-out at 72 hours after blood culture collection and optimized treatment based on the patient's clinical response and test results. The primary outcome was the duration of antibiotic treatment. ResultsIn total, 34 patients in the pharmacist-led ASP group and 32 in the control group were included in the final analysis. The median number of days of antimicrobial treatment was 8 (interquartile range [IQR]: 7-14) days in the pharmacist-led ASP group and 14 (IQR: 10-15) days in the control group. The number of days of antimicrobial treatment significantly reduced in the pharmacist-led ASP group (p < 0.001). The de-escalation rates were 11 (32.4%) cases in the pharmacist-led ASP group and 4 (12.5%) cases in the control group. Hence, the trend was higher in the pharmacist-led ASP group than in the control group (p = 0.08).ConclusionThe pharmacist-led ASP reduced the number of days of antimicrobial therapy for uncomplicated gram-negative bacteremia among patients admitted in a community hospital without an infectious diseases specialist.

Follow-up blood cultures in E. coli and Klebsiella spp. bacteremia-opportunities for diagnostic and antimicrobial stewardship.

Uncomplicated Enterobacteriaceae bacteremia is usually transient and may not require follow-up blood cultures (FUBC). This is a retrospective observational study conducted at a university-affiliated urban teaching hospital in Seattle, WA. All patients ≥ 18years hospitalized between July 2014 and August 2019 with ≥ 1 positive blood culture for either Escherichia coli or Klebsiella species were included. The primary outcome was to determine the number and frequency of FUBC obtained, and the detection rate for positive FUBC. There were 335 episodes of E. coli and Klebsiella spp. bacteremia with genitourinary (54%) being the most common source. FUBC were sent in 299 (89.3%) patients, with a median of 3 (interquartile range (IQR): 2, 4) sets of FUBC drawn per patient. Persistent bacteremia occurred in 37 (12.4%) patients. In uncomplicated E. coli and Klebsiella spp. bacteremia, when the pre-test probability of persistent bacteremia is relatively low, FUBC may not be necessary in the absence of predisposing factors.

259. A Prospective, Stewardship-Driven IV to PO Conversion in Uncomplicated Bacteremia

BackgroundRecent data has shown a transition to oral (PO) antibiotics (ABX) for definitive treatment of uncomplicated bacteremia has similar efficacy compared to continuation of intravenous (IV) ABX, and reduces hospital length of stay (LOS). The purpose of this study was to evaluate the safety and efficacy of an antimicrobial stewardship pharmacist-driven, IV to PO ABX transition in clinically stable patients with uncomplicated bacteremia, and to determine the impact on hospital LOS.MethodsThis was a prospective, interventional study with concurrent controls, conducted at Cedars-Sinai Medical Center between November 2019 and April 2020. For patient recruitment, a report of all positive inpatient blood cultures was reviewed daily. For patients meeting study criteria, the treating provider was contacted to recommend an IV to PO ABX transition. The treating provider was responsible for making the final determination on ABX therapy. Patients continuing IV ABX served as the comparator group to those transitioning to PO.The primary outcome of interest was a composite of: 30-day, all-cause mortality, 30-day readmission due to infectious- or ABX-related complications, or 30-day recurrent infection with the same organism recovered. The second outcome of interest was overall hospital LOS and hospital LOS after the definitive ABX regimen was established.ResultsA total of 117 patients were evaluated; 69 patients met criteria for inclusion in the study (46 PO ABX / 23 IV ABX). Overall, baseline characteristics were similar between the groups. No difference was observed in the 30-day composite outcome (1 in each group), but the median, overall hospital LOS was three days shorter in the PO group. Furthermore, hospital LOS after the definitive ABX regimen was established was four days shorter in the PO group. Based on the differences in hospital LOS observed, the intervention was estimated to have resulted in approximately $819,200 cost-avoidance during the study period.ConclusionSimilar to prior studies, our findings support the safety and effectiveness of an IV to PO ABX transition in clinically stable patients with uncomplicated bacteremia. Antimicrobial stewardship pharmacists can be leveraged to facilitate such a transition.Disclosures All Authors: No reported disclosures

294. Interim Analysis of an Evidence-Based Bundle Intervention for Uncomplicated Enterobacterales Bacteremia

BackgroundUse of evidence-based process bundles for Staphylococcus aureus bacteremia benefit patient outcomes. No studies exist assessing the value of an evidence-based bundle (EBB) in Enterobacterales bacteremia. Recent studies show shorter durations of therapy (DOT) (~ 7 days) result in similar outcomes as longer DOT when treating uncomplicated gram-negative bacteremia. An internal study showed 87% of treatment course durations were > 7 days. This study seeks to determine the impact of an education-based EBB for uncomplicated Enterobacterales bacteremia on patient length of stay (LOS) and DOT.MethodsThis is a quasi-experimental pre- post- analysis conducted across six medical centers. The pre-intervention cohort (n=546) consisted of patients treated for uncomplicated Enterobacterales bacteremia between Jan 1 2016 and Dec 31 2017. The post-EBB education cohort (n=49) consisted of patients treated with the bundle from Jan 1 2020 through Apr 4 2020. Exclusion criteria included immunocompromised state, multiple infection sites, lack of source control, polymicrobial bacteremia, death within 48 hours of treatment, receiving end of life care, < 6 days or > 16 days of therapy, and failure to receive at least one antibiotic with in vitro activity against the organism. The primary outcome was the proportion of patients receiving 6–10 days of therapy. Secondary outcomes included LOS, 30-day readmission rate, 30-day all-cause mortality, time to intravenous to oral conversion, and EBB adherence. Descriptive statistics were used for the baseline characteristics and primary and secondary outcomes. Multiple regression analysis was performed to assess patient covariates.ResultsThere was no difference in the proportion of patients receiving 6–10 days of therapy between the pre- and the post-EBB groups (43.4% vs 53.1%; p = 0.19). There was no association between DOT and covariates. The pre- and post-intervention group had average total DOT of 11.7 ± 2.6 days and 10.6 ± 2.7 days (p = 0.0047), respectively.ConclusionThis interim analysis suggests an education-based EBB for Enterobacterales does not increase the proportion of patients receiving DOT of 6–10 days. Education alone may be insufficient.Disclosures All Authors: No reported disclosures

278. Comparison of Oral Cephalexin Versus Oral Levofloxacin for Treatment of Uncomplicated Enterobacterales Bacteremia

BackgroundAerobic gram-negative rods (GNR) are a common cause of bloodstream infections. While the use of oral antibiotics as step-down therapy for GNR bacteremia is generally accepted, there is debate as to which agents are best. Fluoroquinolones have high oral bioavailability but also have concerns for toxicity, while oral beta-lactams have lower achievable blood concentrations and require more frequent dosing. At Kaweah Delta Medical Center, patients are transitioned from IV antibiotics to oral levofloxacin or cephalexin. The purpose of this study is to determine if these two oral agents are comparable when used as step-down therapy for uncomplicated GNR bacteremia.MethodsThis was a single-center, retrospective study of adult patients who were admitted from May 2018 - May 2019 with a positive GNR blood culture. The primary objective was to assess treatment failure defined as a composite outcome of readmission due to recurrent bacteremia or mortality within 60-days. Secondary outcomes included subsequent Clostridioides difficile infection, emergence of resistant GNR bacteria, and hospital length of stay.ResultsA total of 82 patients met inclusion criteria. The combined median age of both treatment groups was 58.2 years (interquartile range [IQR], 46.7–73.5) and greater than 60% of patients were female. Most patients were Hispanic (45.1%) or non-Hispanic white (43.9%). The most common documented source of GNR bacteremia was the urinary tract (74.4%), and the most frequently recovered organism was Escherichia coli (78.0%). Patients were treated with IV antibiotics for a median treatment duration of 4 days (IQR, 4–5) and oral antibiotics for a median treatment duration of 10 days (IQR, 7.3–11) and 9 days (IQR, 7–11) for cephalexin and levofloxacin, respectively. The composite outcome occurred in 2 patients (4.3%) from the cephalexin group and 0 patients from the levofloxacin group (p=0.50). Positive cultures for resistant GNR were found for 3 patients in the cephalexin group. No patients developed subsequent C. difficile infections. ConclusionPatients who received cephalexin or levofloxacin did not have a significant difference in the composite primary outcome. These findings suggest that oral cephalexin is an effective step-down option to treat uncomplicated GNR bacteremia.Disclosures All Authors: No reported disclosures

52. Development and Implementation of a Short Duration of Antibiotic Therapy Algorithm for Uncomplicated Gram-Negative Bacteremia

BackgroundRecent literature suggests no difference in clinical outcomes between short (7 days) and prolonged course (14 days) antibiotic therapy for the treatment of uncomplicated Gram-negative bacteremia (GNB).MethodsThe objectives of the study were to develop and implement a treatment algorithm that identifies patients who are eligible for 7-day therapy for uncomplicated GNB and evaluate its impact on patient outcomes at The Johns Hopkins Hospital (JHH) in Baltimore. The algorithm was developed and implemented at JHH on 11/11/2019. From 11/11/2019 to 3/31/2020, the Infectious Diseases (ID) Pharmacy Resident and ID pharmacists reviewed cases of GNB on weekdays and contacted teams to provide algorithm-compliant treatment recommendations. To quantify the impact of the intervention on clinical outcomes, data from the same time period during the previous year (baseline) were collected and compared to those collected during the intervention. The primary outcome was duration of antibiotic therapy for GNB. Secondary outcomes included: duration of intravenous (IV) antibiotics, length of hospital stay (LOS), and recurrent bacteremia.ResultsA total of 345 patients with GNB were identified (142 baseline; 203 intervention) of which 59 and 55 patients met criteria for 7-day therapy, respectively. The Pitt bacteremia score (median 1), bacteremia source [urinary (43%), abdominal (23%)], and organisms [E. coli (48%) and Klebsiella spp. (33%)] were similar between the periods. More patients in the intervention period were treated for ≤8 days (60.0% vs. 37.3%; p=0.015), and the median duration of therapy was 2 days shorter (8 vs. 10 days; p=0.04). Median duration of IV antibiotic therapy (4 vs. 7 days; p=0.004) and median LOS (4 vs. 7 days; p=0.029) were also shorter in the intervention period. There were no differences in the rate of 30-day recurrent bacteremia between the periods (3.4% baseline vs. 1.8% intervention; p=0.60).ConclusionOur pharmacist-led intervention successfully shortened the duration of therapy, increased conversion from IV to PO therapy, and reduced LOS, without negatively impacting the number of patients with recurrent GNB.Disclosures All Authors: No reported disclosures

289. Impact of Clinician Specialty on the Use of Oral Antibiotic Therapy for Definitive Treatment of Uncomplicated Bloodstream Infections

BackgroundNo established guidelines exist regarding the role of oral antibiotic therapy (OAT) to treat uncomplicated bloodstream infections (uBSIs) and practices may vary depending on clinician specialty and experience.MethodsAn IRB-exempt web-based survey was emailed to Nebraska Medicine clinicians caring for hospitalized patients, and widely disseminated using social media. The survey was open access and once disseminated on social media, it was impossible to ascertain the total number of individuals who received the survey. Chi-squared analysis for categorical data was conducted to evaluate the association between responses and demographic groups.ResultsOf 275 survey responses, 51% were via social media, and 94% originated in the United States. Two-thirds of respondents were physicians, 16% pharmacists, and infectious diseases clinicians (IDC) represented 71% of respondents. The syndromes where most were comfortable using OAT routinely for uBSI were urinary tract infection (92%), pneumonia (82%), pyelonephritis (82%), and skin/soft tissue infections (69%). IDC were more comfortable routinely using OAT to treat uBSIs associated with vertebral osteomyelitis and prosthetic joint infections than non-infectious diseases clinicians (NIDC), but NIDC were more likely to report comfort with routine use of OAT to treat uBSIs associated with meningitis and skin/soft tissue infections. IDC were more likely to report comfort with routine use of OAT for uBSIs due to Enterobacteriaceae and gram-positive anaerobes, while NIDC were more likely to be comfortable with routinely using OAT to treat uBSIs associated with S. aureus, coagulase-negative staphylococci and gram-positive bacilli. In one clinical vignette of S. aureus uBSI due to debrided abscess, 11% of IDC would be comfortable using OAT vs 28% of NIDC; IDC were more likely to report routinely repeating blood cultures (99% vs 83%, p< 0.05).Figure 1: Clinician comfort using oral antibiotic therapy to treat uncomplicated bacteremia due to specific syndromes Figure 2: Clinician comfort using oral antibiotic therapy to treat uncomplicated bacteremia due to specific organisms ConclusionConsiderable variation in comfort using OAT for uBSIs among IDC vs NIDC exists, highlighting opportunities for IDC to continue to demonstrate their value in clinical practice. Understanding the reasons for variability may be helpful in creating best practice guidelines to standardize decision making.Disclosures All Authors: No reported disclosures

Outcomes of Extended-Spectrum Beta-Lactamase Gram-Negative Bacteremia Cases Treated With Carbapenem Versus Noncarbapenem Antibiotics

Background: The rising prevalence of infections caused by extended-spectrum β-lactamase (ESBL)–producing bacteria increases reliance on carbapenems, which intensifies selection pressure for the emergence of carbapenem-resistant Enterobacteriaceae (CRE). Whether noncarbapenem (nC) antibiotics can be safely used in this setting remains incompletely understood. Objective: To examine the safety of carbapenem stewardship in this population, we compared outcomes of uncomplicated ESBL bacteremia treated with a carbapenem to those treated with a noncarbapenem regimen. Methods: A retrospective chart review of patients with ESBL bacteremia from 2014 to 2018 in a 5-hospital regional health system was conducted. Patients aged &lt;18 years, with polymicrobial bacteremia, whose infections required a prolonged length of antibiotic therapy (LOT), or who died on antibiotic treatment or transitioned to hospice, were excluded. Groups were stratified based on the antibiotic regimen with the highest number of treatment days during the treatment course. Outcome measures included empiric and definitive length of therapy (LOT), 30-day all-cause mortality, 90-day readmission, recurrence of ESBL bacteremia, hospital length of stay (LOS), incidence of Clostridioides difficile infection (CDI) and adverse drug events, obtained by Wilcoxon rank-sum testing, χ2 test, and Fisher exact test, as applicable. Results: In total, 112 unique patients had ESBL bacteremia; 42 were excluded, leaving 70 for analysis. Of these, 57 were treated with a carbapenem regimen and 13 patients were treated with a noncarbapenem regimen: 9 ciprofloxacin, 3 gentamicin, 1 TMP-SMX. Patient baseline and antibiotic regimen characteristics were similar (Table 1). The most common organism was E. coli, and the most common source was urinary. A similar proportion of each group received ESBL-active empiric antibiotics. There were no significant differences in total effective antibiotic LOT, 30-day all-cause mortality, 90-day readmission, or recurrence of ESBL bacteremia (Table 2). A nonsignificant trend in hospital LOS was observed in the noncarbapenem group (11 vs 6 days; P = .055). Conclusions: Although the sample size was small, these multicenter data suggest that noncarbapenem treatment of ESBL bacteremia may be safe and effective. Pending confirmatory studies, ESBL bacteremia may be an important target for carbapenem stewardship.Funding: NoneDisclosures: None

ONE FOR THE MONEY, TWO FOR THE ECMO: A SUCCESSFUL PHARMACOTHERAPEUTIC STRATEGY FOR VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM AND CANDIDA GLABRATA FUNGEMIA IN VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION AND CONTINUOUS RENAL REPLACEMENT

SESSION TITLE: Fellows Critical Care Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) are modalities with a relative paucity in understanding of the disposition of antimicrobials, and even less for when used simultaneously. Preliminary investigations have demonstrated that ECMO leads to pharmacokinetic changes, which include alterations in volume of distribution, drug clearance, and sequestration by the circuit.1 CASE PRESENTATION: Our patient was a 66-year-old-male with a history of alcohol use disorder, transferred to our hospital for acute respiratory distress syndrome due to influenza A pneumonia with superimposed bacterial pneumonia, cannulated for venous-venous ECMO. Encephalopathy, atrial fibrillation, pulmonary embolisms, distributive shock, and anuric acute kidney injury requiring CRRT complicated his course. Following a prolonged course, blood cultures were obtained and Candida glabrata and vancomycin resistant Enterococcus faecium (VRE) were isolated. We initiated high dose micafungin 150 mg IV q 24 h, high dose, high frequency daptomycin 10 mg/kg IV q 24 h. An echocardiogram, Ophthalmology consult, and repeat blood cultures were also requested to document clearance of fungemia and bacteremia. A trans-esophageal echocardiogram was performed, without evidence of masses or vegetations. Fundal exam did not show any signs of fungal endophthalmitis. Repeat cultures were without growth, all existing IV lines were exchanged except for ECMO cannulas. His leukocytosis began to downtrend, and he became afebrile after start of antimicrobial therapy. Given that his most likely source of infection was line associated, a two-week antimicrobial course for uncomplicated fungemia and bacteremia was recommended. DISCUSSION: We hope to add to the limited data on daptomycin and micafungin dosing strategies for patients on ECMO and CRRT. A thorough understanding of the altered pharmacokinetics is essential to apply in these complex patients. Daptomycin has a low volume of distribution, and it is highly protein bound, making it less likely to be affected by ECMO. It is known that for patients on CRRT, daptomycin dosing q 24 h up to 12 mg/kg provides comparable drug exposure to patients with a CrCl = 30 mL/min,2 therefore, a dose of 10 mg/kg q 24 h was deemed appropriate to treat our patient. Creatinine kinase was monitored weekly without any changes from baseline. Micafungin is highly protein bound, minimally renally cleared and does not require CRRT dose adjustment. CONCLUSIONS: Prior studies in ECMO patients have shown decreased plasma concentrations due to drug degradation and increased clearance,3 which warrant a dose increase. As such, micafungin 150 mg q 24 h was used in our patient. This report highlights the need for more research on optimal dosing strategies of antimicrobials in this patient population. Reference #1: Cheng V, Abdul-Aziz MH, Roberts JA, Shekar K. Optimising drug dosing in patients receiving extracorporeal membrane oxygenation. J Thorac Dis. 2018;10(Suppl 5):S629-S641. Reference #2: Xu X, Khadzhynov D, Peters H, et al. Population pharmacokinetics of daptomycin in adult patients undergoing continuous renal replacement therapy. Br J Clin Pharmacol. 2017;83(3):498-509. Reference #3: Watt KM, Cohen-Wolkowiez M, Williams DC, et al. Antifungal extraction by the extracorporeal membrane oxygenation circuit. J Extra Corpor Technol. 2017;49(3):150-159. DISCLOSURES: No relevant relationships by M. Gabriela Cabanilla, source=Web Response No relevant relationships by Nicholas Villalobos, source=Web Response

Short-course versus long-course antibiotic treatment in patients with uncomplicated gram-negative bacteremia: A systematic review and meta-analysis.

What is known and objectiveGram‐negative bacteremia remains a major health problem around the world. The optimal duration of antibiotic treatment has been poorly defined, and there are significant differences of opinion between clinicians. We conducted this systematic review and meta‐analysis to compare the clinical outcomes of short‐course and long‐course treatments in patients with uncomplicated gram‐negative bacteremia.MethodsWe searched public databases (PubMed, EMBASE and Cochrane Library) to identify eligible studies. The primary outcomes were all‐cause mortality and the incidence of recurrent bacteremia through day 30. We used the Cochrane risk of bias assessment tool to evaluate the risk of bias for randomized controlled trials (RCTs) and the Newcastle‐Ottawa Scale for non‐RCTs.Results and discussionSix studies involving 2689 patients were included in the systematic review and meta‐analysis. No significant difference was found between short‐course and long‐course antibiotic treatments in 30‐day mortality (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.65‐1.13; P = .26), 30‐day recurrent bacteremia (RR 1.07; 95% CI 0.68‐1.67; P = .78), 90‐day mortality (RR 0.84; 95% CI 0.57‐1.24; P = .38), 90‐day recurrent bacteremia (RR 0.98; 95% CI 0.50‐1.89; P = .94), adverse events (RR 1.14; 95% CI 0.89‐1.45; P = .30), Clostridium difficile infection (RR 0.86; 95% CI 0.40‐1.86; P = .71) or resistance development (RR 1.19; 95% CI 0.66‐2.14; P = .57).What is new and conclusionShort‐course was non‐inferior to long‐course antibiotic treatments for patients with uncomplicated gram‐negative bacteremia. Considering the drug‐related side effects and cost‐effectiveness, a shorter duration of antibiotic treatment may be preferable for this particular population. However, additional high‐quality RCTs are needed to further assess whether a shorter course of antibiotic treatment is of greater benefit for patients with uncomplicated gram‐negative bacteremia.

The Changing Landscape of Uncomplicated Gram-Negative Bacteremia: A Narrative Review to Guide Inpatient Management.

Gram-negative bacteremia secondary to focal infection such as skin and soft-tissue infection, pneumonia, pyelonephritis, or urinary tract infection is commonly encountered in hospital care. Current practice guidelines lack sufficient detail to inform evidence-based practices. Specifically, antimicrobial duration, criteria to transition from intravenous to oral step-down therapy, choice of oral antimicrobials, and reassessment of follow-up blood cultures are not addressed. The presence of bacteremia is often used as a justification for a prolonged course of antimicrobial therapy regardless of infection source or clinical response. Antimicrobials are lifesaving but not benign. Prolonged antimicrobial exposure is associated with adverse effects, increased rates of Clostridioides difficile infection, antimicrobial resistance, and longer hospital length of stay. Emerging evidence supports shorter overall duration of antimicrobial treatment and earlier transition to oral agents among patients with uncomplicated Enterobacteriaceae bacteremia who have achieved adequate source control and demonstrated clinical stability and improvement. After appropriate initial treatment with an intravenous antimicrobial, transition to highly bioavailable oral agents should be considered for total treatment duration of 7 days. Routine follow-up blood cultures are not cost-effective and may result in unnecessary healthcare resource utilization and inappropriate use of antimicrobials. Clinicians should incorporate these principles into the management of gram-negative bacteremia in the hospital.