Relapse Of Bacteremia Research Articles

P-1172. Staphylococcus Aureus Long-Term Catheter-Related Bloodstream Infection in Children: Clinical Features and Outcome

Abstract Background Staphylococcus aureus long-term catheter-related bloodstream infection (LT-CRBI) are a frequent cause of morbidity and mortality. In Staphylococcus aureus LT-CRBI, it is recommended to remove the catheter. However, in pediatrics, management without catheter removal is often necessary. Aims to describe the clinical characteristics and outcome of Staphylococcus aureus LT- CRBI, to cmpare the clinical features and outcome according to removal or retention of the catheter Methods Retrospective cohort study. All patients with Staphylococcus aureus LT-CRBI from 1/1/2018 to 12/31/2022 in a pediatric hospital were included. Episodes of relapse of bacteremia were excluded. LT-CRBI was defined according to CDC criteria. Results Forty-five patients were included. Median age was 80 months (IQR 27-137). All patients had any underlying disease. Most common comorbidities were onco-hematological disease 27 patients (60%), intestinal failure 5 (11%), chronic kidney disease 3 (7%). Thirty-three were under immunosuppressive treatment (73%). Median length of bacteremia was 4 days (IQR 3-5) Five patients presented metastatic infection (11%) including 2 patients with pneumonia, 2 thrombophlebitis and 1 soft tissue infection. Twenty-two catheters (49%) were removed. Reasons for removal were: mechanical dysfunction in 6 patients, catheter was not being used in 5 patients, tunnel or pocket infection in 5, septic shock 3 and persistent bacteremia in 3. Two patients died related to infection (4%). Staphylococcus aureus methicillin sensitive predominated (78%). Comparing patients with catheter removal vs retained: there were no differences in epidemiological, clinical features and outcome (metastatic infection 13% vs 9%, intensive care admission 3% vs 3%, length of bacteremia 4 days in both groups, mortality 20% vs 17%, respectively) Conclusion In this cohort of children with Staphylococcus aureus LT- CRBI, catheters were maintained in 51% of patients. No difference in outcome or complications was observed. Disclosures All Authors: No reported disclosures

Length of Hospital Stay for Endocarditis Before and After the Partial Oral Treatment of Endocarditis Trial

BackgroundThe results from the POET (Partial Oral Treatment of left-sided Endocarditis) trial were published in August 2018 and established noninferiority of oral step-down antibiotic treatment in stabilized patients with infective endocarditis (IE). Data on length of hospital stay (LOS) and safety following the POET trial are warranted. ObjectivesThe goal of this study was to examine changes in LOS and safety (mortality and relapse of bacteremia) before and after POET publication. MethodsUsing Danish nationwide registries, patients with first-time IE caused by Streptococcus spp., Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci from 2012 to 2021 were identified. Median LOS was examined according to publication date (before and after September 2018). Mortality and relapse of bacteremia at 180 days of follow-up were examined. ResultsWe identified 3,008 patients before POET publication (median age 72.8 years) and 1,740 after publication (median age 75.2 years) (P < 0.0001). The median LOS decreased by 8 days: 41 days (Q1-Q3: 29-49 days) before POET publication and 33 days (Q1-Q3: 21-44 days) after POET publication (P < 0.0001). Similar reductions in LOS were seen across microbiological etiologies and age groups. Reduction in LOS was most pronounced in nonsurgically treated patients. Mortality from IE admission to a maximum of 180 days’ follow-up was 27.5% before POET publication and 28.3% after publication (P = 0.41). The bacteremia relapse rate within 180 days was 3.5% before POET publication and 1.6% after publication (P = 0.0002). ConclusionsFollowing the POET trial, we found a reduction in median LOS of 8 days with no change in mortality and an associated lower rate of relapse of bacteremia.

Changes in length of hospital stay for infective endocarditis - data from before and after the POET trial

Abstract Background The results from the Partial Oral Treatment of left-sided Endocarditis (POET) trial was published in August 2018 and established non-inferiority of a switch to oral step-down antibiotic treatment in stabilized patients with infective endocarditis (IE). However, data on length of hospital stay and safety following the POET trial are warranted. Purpose To examine the changes in length of hospital stay before and after POET publication. Further, to assess safety (relapse of bacteremia and 180 days of mortality) before and after POET publication. Methods By cross-linkage of Danish nationwide registries, patients with first-time IE caused by Streptococcus spp., Enterococcus faecalis, Staphylococcus aureus, or coagulase negative staphylococci from 2012-2021 were identified. Immediately following the publication of the POET trial, the POET criteria was implemented and used in Denmark. The study period was categorized according to publication date (before and after September 2018). Median length of hospital stay was examined according to calendar period. Mortality (from admission date) and relapse of bacteremia (after discharge) at 180 days of follow-up were examined with the Kaplan-Meier estimator and the Cumulative Incidence Function, respectively. Results We identified 3,008 patients before publication of the POET trial (median age 72.8 years) and 1,740 after the publication (median age 75.2 years) (p&amp;lt;0.0001). The burden of comorbidities was comparable between groups. The median length of hospital stay decreased by 8 days: 41 days (IQR: 29-49) before POET publication and 33 days (IQR: 21-44) after POET publication (p&amp;lt;0.0001 for difference), Figure 1. Similar reductions in length of hospital stay were seen across different microbiological etiologies and age groups. The reduction in length of hospital stay was most pronounced in non-surgically treated patients. The mortality from IE admission with a maximum of 180 days follow-up was 27.5% before POET publication and 28.3% after POET publication (p-value=0.41 for difference). The bacteremia relapse rate within 180 days was 3.5% before POET publication and 1.6% after POET publication (p-value=0.0002 for difference), Figure 2. Conclusion Following the POET trial, we found an 8 days reduction in median length of hospital stay with no change in mortality and an associated lower rate of relapse of bacteremia.

Seven-day antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients: toward a new paradigm.

Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14days. This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14days of AT. Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9days (IQR: 7-15) vs. 14days (IQR: 13-22) (p = < 0.001). These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.

2409. Potential candidates for partial oral treatment in patients with endocarditis at a US center

Abstract Background In the Danish POET trial, oral step-down oral antibiotics in patients with left-sided infective endocarditis (IE) was non-inferior to traditional intravenous antibiotics (IV-AB). Outpatient parenteral antimicrobial therapy (OPAT) is widely used in the US despite associated adverse events. Our aim was to assess the proportion of US patients that were potential candidates for step-down oral antibiotic treatment, i.e. POET-treatment, and number of days IV-AB antibiotics could have been reduced. Methods Retrospective study of patients admitted with left-sided IE at a US single center from January 2021 – June 2022 was conducted. Patients were considered candidates for POET-treatment if they were infected with S. aureus, E. faecalis, Streptococcus spp., or CoNS, had a BMI &amp;lt; 40 kg/m2 and survived until discharge. The primary outcome was a composite of all-cause mortality, symptomatic embolism, unplanned cardiac surgery, and relapse of bacteremia within 6 months. Results Out of 111 patients with left-sided IE, 71 (64%) were considered potential POET-candidates (median age 64 years (IQR 54-75), 72% male); 30% had IE caused by S. aureus, and 48% were surgically treated (Table 1). Potential candidates were older (64 vs 60 years), more often infected with Streptococcus spp. (24% vs 0%) or CoNS (23% vs 5%), and had a pacemaker/ICD at baseline (23% vs 5%), as compared to patients who were not candidates for POET-treatment. Of potential POET-candidates, 93% (66/71) were stabilized, allowing discharge to OPAT with a median of 29 days (IQR 20-36) of antibiotic treatment remaining. The primary outcome occurred in 28% of potential POET-candidates and in 53% of non-POET candidates, compared to the occurrence of the primary outcome in 11% in the Danish POET-trial (Table 2). Conclusion More than half of patients admitted with left-sided IE were potential candidates for POET-treatment. For the vast majority of these patients, up to 4 weeks of IV-AB may have converted to oral step-down antibiotics. Prevalence of the primary outcome in potential POET-candidates was almost 3 times higher in this US cohort than in the Danish POET trial, indicating a higher baseline risk. These findings indicate a need for prospective studies of oral step-down antibiotic therapy in US patients with IE. Disclosures Joji Suzuki, MD, Indivior: Grant/Research Support

Abstract 17647: Potential Candidates for Partial Oral Treatment in Patients With Endocarditis at a US Center

Introduction: In the Danish POET trial, oral step-down antibiotic therapy was non-inferior to intravenous antibiotic therapy (IVAB) in stabilized patients with left-sided infective endocarditis (IE). It is unknown whether oral treatment for IE can be efficacious in the US population. Aim Identify patients with IE who may have been candidates for POET treatment in a US cohort and assess the reduction of IVAB days and differences in characteristics and outcomes compared to participants in the POET trial. Methods: Retrospective study of patients admitted with IE at a US single center in Jan 2021 - July 2022. Possible candidates for POET treatment were patients with left-sided IE and infection with S. aureus , E. faecalis , Streptococcus , or coagulase-negative staph (CoNS), who had reached stabilization of infection or were discharged. Primary outcome was a composite of all-cause mortality, relapse of bacteremia, embolism or unplanned cardiac surgery within 6 months. Results: Of 152 patients with IE, 90 (59%) were possible candidates for POET treatment. Median length of IVAB after stabilization was 33 days (IQR 24-37). Compared to POET-trial patients, POET candidates in the US cohort were younger (64 vs 70 years), more often had diabetes (30% vs 17%), cancer (30% vs 8%), intravenous substance use (8% vs 1%) or pacemakers (18% vs 9%) [Table]. Prevalence of S. aureus (35% vs 22%) and CoNS infections (23% and 6%) was higher; Streptococcus was less common (30% vs 49%). Primary outcome occurred in 25 patients (28%) compared to 42 patients (10%) in the POET-trial (p&lt;0.001). Conclusions: More than half of patients admitted with IE were possible POET candidates, for whom 4 weeks of IVAB may have been converted to oral antibiotics. Candidates in the US cohort had more comorbidities and primary outcome was three times higher than in the POET trial. Prospective studies are needed for verification of POET treatment in higher-risk US IE patients.

Impact of Adding a Rapid PCR-Based Blood Culture Identification Panel to the Antimicrobial Stewardship Program of Patients with Febrile Neutropenia in a Peruvian Referral Hospital.

The addition of Biofire® FilmArray® Blood Culture Identification panel 2 (BCID2) to the antimicrobial stewardship program (ASP) could improve outcomes in bloodstream infections (BSI) of patients with febrile neutropenia (FN). A pre- and post-quasi-experimental single-center study was conducted at a reference hospital in Peru. Three groups were considered: patients with BSI before ASP intervention (control group), patients with BSI after ASP intervention (group 1), and patients with BSI after ASP intervention plus BCID2 PCR Panel implementation (group 2). Overall, 93 patients were identified (32 control, 30 group 1, 31 group 2). The median time to effective therapy was significantly shorter in group 2 compared to group 1 and control group, respectively (3.75 vs. 10 h, p = 0.004; 3.75 vs. 19 h, p < 0.001). No significant differences in terms of relapse of bacteremia, in-hospital mortality (all cause), and 30-day-all-cause hospital readmission between the three study periods were found. The appropriateness of empirical antimicrobial use, adding or change, and the following de-escalation or discontinuation was significant when the two intervention periods were compared with the control group (p < 0.001). In addition to the lack of local studies documenting the microbiological profile of FN episodes, adding syndromic panels-based testing could allow for the consolidation of ASP strategies.

Short Course of Antibiotic Therapy for Gram-Negative Bacilli Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation: Less Is Possible.

Data about short courses of antibiotic therapy for Gram-negative bacilli (GNB) bacteremia in immunosuppressed patients are limited. This is a prospective observational study performed on adult patients with cancer and hematopoietic stem cell transplant (HSCT) who developed GNB bacteremia and received appropriate empirical antibiotic therapy (EAT), had a clinical response within 7 days and survived 48 h after the end of therapy. They received antibiotic therapy in the range of 7-15 days and were divided into short course, with a median of 7 days (SC), or long course, with a median of 14 days (LC). Seventy-four patients were included (SC: 36 and LC: 38). No differences were observed in baseline characteristics or in the presence of neutropenia: 58.3% vs. 60.5% (p = 0.84). Clinical presentation and microbiological characteristics were similar in SC and LC, respectively: clinical source of bacteremia 72.2% vs. 76.3% (p = 0.68); shock 2.8% vs. 10.5% (p = 0.35) and multidrug-resistant GNB 27.8% vs. 21.1% (p = 0.50). Overall, mortality was 2.8% vs. 7.9% (p = 0.61), and bacteremia relapse was 2.8% vs. 0 (p = 0.30). The length of hospitalization since bacteremia was 7 days (interquartile range (IQR), 6-15) for SC and 12 days (IQR, 7-19) (p = 0.021) for LC. In the case of patients with cancer or HSCT and GNB bacteremia who receive appropriate EAT with clinical response, 7 days of antibiotic therapy might be adequate.

Duration of antibiotic treatment for Gram-negative bacteremia - Systematic review and individual participant data (IPD) meta-analysis.

We aim to compare the effect of short versus long treatment duration in Gram-negative bacteremia on all-cause mortality in pre-specified sub-groups. Individual participant data meta-analysis of randomized controlled trials (RCTs) comparing short (≤7) versus longer (>7 days) antibiotic treatment for Gram-negative bacteremia. Participants were adults (≥18 years), with Gram-negative bacteremia during hospital stay. We searched PubMed, Cochrane Central Register of Controlled Trials, and Web of Science to identify trials conducted up to May 2022. Primary outcome was 90-day all-cause mortality. Secondary outcomes were 30-day mortality, relapse of bacteremia, length of hospital stay, readmission, local or distant infection complications, adverse events, and resistance emergence.Outcomes were assessed in pre-specified subgroups: women vs men; non-urinary vs urinary source; presence vs absence of hypotension on initial presentation; immunocompromised patients versus non-immunocompromised patients, and age (above/below 65). Fixed-effect meta-analysis model was used to estimate pooled odds ratio (OR) and 95% confidence interval (CI). All three trials had low risk of bias for allocation generation and concealment. Three RCTs (1186 patients) were included; 1121 with enterobacterales bacteremia. No significant difference in mortality was demonstrated between 7- and 14-days treatment (90-day mortality: OR 1.08, 95% CI 0.73-1.58; 30-day mortality: 1.08, 0.62-1.91). Relapse (1.00, 0.50-1.97); length of hospital stay (P=0.78); readmission (0.96, 0.80-1.22); and infection complications (local: 1.62 0.76-3.47; distant: 2.00, 0.18-22.08), were without significant difference, and so were adverse events or resistance emergence.No significant difference in clinical outcomes between 7 and 14 days of antibiotics was demonstrated in the subgroups of gender, age, hemodynamic status, immune status, and source of infection. For patients hemodynamically stable and afebrile at 48h prior to discontinuation, seven days of antibiotic therapy for enterobacterales bacteremia result in similar outcomes as 14 days, in terms of mortality, relapse, length of hospital stay, complications of infection, resistance emergence, and adverse events. These results apply for any adult age group, gender, source of infection, immune status, and hemodynamic status on presentation. There was no funding source for this study.

Long-term impact of persistent vegetations at 6 month followup after treatment of infective endocarditis: a substudy of the Partial Oral vs Intravenous Antibiotic Treatment of Endocarditis (POET) tria

Abstract Background Our knowledge of changes in vegetation size throughout the course of infective endocarditis (IE) and the impact of persistent vegetations on mortality or embolization after completed antibiotic treatment is sparse. No study has previously investigated the prevalence or clinical impact of persistent vegetations on transthoracic echocardiography (TTE) at 6-months follow-up after ended IE treatment. Purpose To investigate the association between persistent vegetations at the 6-months TTE after treatment for IE and long-term prognosis as assessed in the POET trial. Methods The POET trial was a nationwide, multicenter RCT, randomizing 400 patients to either partial oral or intravenous (IV) antibiotic treatment of left-sided IE, after initial stabilization of infection using conventional IV therapy. A persistent vegetation was defined as a vegetation seen on 6-months follow-up TTE (4–7 months) after ended antibiotic treatment for IE. In the POET trial, primary outcome was defined as 1) all-cause mortality, 2) unplanned cardiac surgery, 3) embolic events or 4) relapse of bacteremia, in the 5-year follow-up period. Patients without TTE due to death or lack of available TTE were excluded. Results Out of 400 patients, 20 were excluded due to death during 6-months follow-up, and 201 were excluded due to unavailable TTE, leaving 179 TTEs for analysis. At 6-months follow-up, a persistent vegetation was seen in 30 patients (16.7%, 21 males (70%), mean age 69.6 years (SD 7.7)) (Table 1). Seventeen patients (56.7%) had a persistent vegetation on the aortic valve and 13 patients (43.3%) on the mitral valve. More patients without a persistent vegetation had undergone initial surgical treatment of IE than those with a vegetation (57.7 vs 23.3%, p=0.001). In all surgically treated patients with persistent vegetation at 6-months follow-up, the vegetation was found on another valve than the operated valve. The composite primary outcome from 6-months follow-up and until 5-year follow-up occurred in 8 patients (26.7%) with a persistent vegetation, compared to 38 patients (25.5%) (p=1.00) without. (Table 2) In patients randomized for peroral treatment, no significant difference in prevalence of persistent vegetation was found (15 patients (50%) with persistent vegetations vs. 74 patients (49.7%) without, p=1.00). Conclusion The occurrence of persistent vegetations at 6 months follow-up was 16.7%. There was no association between persistent vegetations at 6-months follow-up and the occurrence of the primary outcome after 5 years follow-up, suggesting that the risk associated with residual vegetations after end of antibiotic treatment is negligible after 6-months. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation

Clinically unsuspected orthopedic implants during S. aureus bacteremia do not require additional diagnostic work-up

PurposeTo assess the likelihood of occult infection in patients with clinically unsuspected orthopedic implants during Staphylococcus aureus bacteremia (SAB).MethodsIn a retrospective study in two Dutch hospitals, we included all patients with SAB between 2013 and 2020 with one or more orthopedic implants in whom [18F]FDG-PET/CT was performed. The primary outcome was the percentage of patients who had an orthopedic implant-related infection by S. aureus. We also compared clinical parameters in patients with clinically suspected and unsuspected implants.ResultsFifty-five of 191 (29%) orthopedic implants in 118 SAB patients included had clinical signs of infection. Of all 136 unsuspected implants, 5 (3%, all arthroplasties), showed increased [18F]FDG uptake around the prosthesis on [18F]FDG-PET/CT. The clinical course of these patients without clinically overt infection or relapse of bacteremia during follow-up of a median of 48 months (range 0–48), however, argued against prosthetic joint infection.ConclusionAlthough orthopedic implants are evidently a risk factor for metastatic infection during SAB, the absence of clinical symptoms obviate the need of additional investigations or prolonged antibiotic treatment.

A retrospective study of Enterococcus faecalis infective endocarditis: comparison of clinical characteristics and outcomes associated with treatment.

IntroductionA synergistic antibiotic combination of a penicillin and gentamicin (AG) or ceftriaxone (AC) is used in the management of Enterococcus faecalis infective endocarditis (EFIE). We compare the treatment outcomes between AG and AC, including low and high dose ceftriaxone (1 and 2 g 12 hourly).MethodsA retrospective cohort study of patients treated for EFIE at single tertiary centre (2012–2019). Outcome measures examined were 90- and 180-day mortality, treatment associated adverse events and relapse of bacteraemia (within 1 year).Results39 patients were enrolled [61.6% given (AC) (n = 24), 24% received ACL (n = 10) and 34% received ACN (n = 14)], 38.4% received AG (n = 15). We noted a difference in the mortality outcomes at 90 and 180 days between those treated with AG and AC overall (6.7% and 33.3%, respectively) although this did not reach statistical significance (P = 0.114, P = 0.061). No significant difference was noted between these groups in incidence of relapsed bacteraemia with two cases noted in the AC cohort (8.3%, 2/24) and none observed (0/15) in the AG cohort (P = 0.662, P = 0.414). A greater number of adverse events was observed in the AG group (11/15, 73.3%) compared to the overall AC group (6/24, 25.0%) (P = 0.009), with no difference between the high and low dose ceftriaxone groups (P = 0.05).ConclusionCombination treatment of EFIE with AC is associated with a reduced number of adverse events in comparison to AG groups. Although increased mortality was observed in the AC group, this did not reach statistical significance, and reflects the greater comorbidities and reduced capacity for surgical source control in this cohort.

Genomic identification of streptococcal strains and relation to clinical characteristics. A substudy to The Partial Oral Treatment of Endocarditis (POET) Trial.

The Danish National Partial Oral Treatment of Endocarditis Trial (POET) demonstrated non-inferiority of partly peroral compared to intravenous antibiotic therapy for infective endocarditis (IE) caused by Streptococcus spp, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci. Identifications by whole genome sequencing (WGS) of available streptococcal strains were related to clinical data. Sequences were obtained using Illumina technology (MiseqÒ) followed by core genome analysis and single-nucleotide polymorphism phylogeny examinations. Average nucleotide identification (ANI) calculated using the tool fastANI. Informations on +/- preexisting valve prosthesis, valve surgery and outcome related to obtained identifications. Streptococcal strains (n=123) from 117 patients were WGS examined. Twelve percent were pyogenic group strains and 88% belonged to viridans groups, mainly mitis and bovis groups. Phylogenetic trees were in accordance regarding species and subspecies identifications. High ANI percentages to type strains were found. Respectively 39, 60 and 16 IE cases involved mitral, aortic or both valves. IE caused by pyogenic group or mitis plus bovis group streptococci most frequent affected, respectively, mitral and aortic valves. Thirty-one patients (26%) had a preexisting prosthesis; notably, in 50% of bovis group IE cases. Fifty-six patients had valve surgery done during the current disease; 8% and 93% of patients having, respectively, pyogenic group and mitis group strains as causative agents. Of patients allocated to intravenous or intravenous followed by peroral antibiotic treatment, respectively 26 and 30 had valve surgery done during the current disease. Composite outcome (all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen) at five-year follow-up comprised in total 39 events. In conclusion, molecular examinations adds on substantially by detailing species and subspecies affiliations. A broad spectrum of streptococcal species and subspecies causing IE were identified with mitis- and bovis group strains dominating. Relating strain identifications to clinical data can assist in planning and treating confirmed/suspected IE patients. Adding WGS identification of streptococci in selected patients groups (e.g. IE) in order to expand number of cases characterized in detail seems ideal and advocates for centralized registration of results to reveal important clinical relations.

204. Clinical Outcomes with Ceftaroline Monotherapy versus Daptomycin-Ceftaroline Combination Therapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with poor outcomes and increased mortality. Daptomycin (DAP) and ceftaroline (CPT) in combination has been explored as a potential treatment option and showed improved outcomes compared to vancomycin/standard therapy. CPT monotherapy has been evaluated as salvage therapy for MRSA bacteremia but, to our knowledge, not as a comparator to DAP-CPT combination therapy. The purpose of this study is to compare the clinical outcomes of DAP and CPT combination therapy to CPT monotherapy in the setting of MRSA bacteremia. MethodsA retrospective chart review of adult patients (≥ 18 years of age) admitted to University Health from January 2017 to December 2020 with a diagnosis of MRSA bacteremia was performed. Patients received either CPT monotherapy or DAP-CPT combination therapy for a minimum of 48 hours during their course of therapy. ResultsThirty-two patients met inclusion criteria and were evaluated. Primary source of infection was pulmonary in the CPT monotherapy group (n=7/24; 29.2%) and osteomyelitis in the DAP-CPT combination group (n= 4/8; 50.0%). Median duration of bacteremia was 8 days and 9 days in the CPT monotherapy and DAP-CPT combination group, respectively. Microbiological cure was achieved in 95.8% (n=23/24) of patients in the CPT monotherapy and 100% (n=8/8) of patients in the DAP-CPT combination group. Bacteremia relapse (30 day, p=0.62; 60 day, p=0.63), readmission rates (30 day, p=0.62; 60 day, p=0.63), and mortality rates (30 day, p=0.70; 90 day, p=0.85) were similar in both groups. There was no statistically significant difference in safety parameters, including incidence of acute kidney injury (p=1.00) and creatine kinase elevations (p=1.00). Bone marrow suppression after at least 72 hours of therapy, including anemia, leukopenia, and thrombocytopenia, was also not statistically significant between groups. ConclusionThis study was unable to find a statistically significant difference in clinical outcomes between patients receiving CPT monotherapy or DAP-CPT combination therapy. A large prospective, randomized controlled trial to assess CPT monotherapy and DAP-CPT combination therapy for the treatment of persistent MRSA bacteremia is warranted. Disclosures All Authors: No reported disclosures

Ampicillin-Ceftriaxone vs Ampicillin-Gentamicin for Definitive Therapy of Enterococcus faecalis Infective Endocarditis: A Propensity Score-Matched, Retrospective Cohort Analysis.

BackgroundAmpicillin-ceftriaxone (AC) has emerged as an alternative antibiotic regimen for enterococcal infective endocarditis (EIE) with reduced toxicity compared with ampicillin-gentamicin (AG), but evidence regarding its success in reducing EIE-associated death in the United States is limited.MethodsWe conducted a retrospective, propensity score–matched cohort analysis of EIE patients treated with AC or AG between 2010 and 2017 at 3 hospitals in Pittsburgh, Pennsylvania. We assessed all-cause 90-day mortality as the primary outcome and in-hospital mortality, length of hospital stay, hospital readmissions, adverse events, and relapse of bacteremia as the secondary outcomes.ResultsA total of 190 patients with EIE (100 treated with AC and 90 with AG) were included. Ninety-day mortality was significantly higher with AC than AG (21% vs 8%; P = .02). After propensity score matching, 56 patients in each group remained for the outcomes analysis. Documented aminoglycoside resistance, presence of annular or aortic abscess, and complete pacemaker removal were the significantly different variables between the 2 matched cohorts. We observed no statistically significant difference in 90-day mortality between the 2 treatment groups (11% vs 7%; P = .55). Adverse events were more common in patients treated with AG (25 vs 39; P = .0091), and more patients in the propensity score–matched AG cohort switched antibiotic regimens than in the AC group (10% vs 49%; P < .0001).ConclusionsPatients treated with AC demonstrate no significant differences in mortality, treatment failure, or bacteremia relapse compared with AG in a propensity score–matched EIE cohort.

700. Ampicillin-Ceftriaxone Versus Ampicillin-Gentamicin for Definitive Therapy of Enterococcus faecalis Infective Endocarditis: A Propensity Score-Matched,Retrospective Cohort Analysis

BackgroundThe mortality rate for Enterococcus faecalis infective endocarditis (EIE) is high. Ampicillin-ceftriaxone (AC) has emerged as an alternative antibiotic regimen with lower toxicity compared to ampicillin-gentamicin (AG), but evidence regarding its success in reducing EIE-associated mortality in the United States is limited. We retrospectively compared mortality in EIE patients treated with AG versus AC.MethodsWe conducted a retrospective, propensity score-matched, cohort analysis of EIE patients treated with AG or AC from 2010 to 2017 at three hospitals in Pittsburgh, Pennsylvania. Patients were included in the analysis if they were treated for EIE with either AC or AG as the pathogen-directed antibiotic regimen for at least forty-eight hours. We assessed 90-day mortality as the primary outcome, and in-hospital mortality, length of hospital stay, hospital readmissions, adverse events, and relapse of bacteremia as the secondary outcomes.ResultsA total of 190 patients with EIE (100 treated with AC and 90 with AG) were included. Ninety-day mortality was significantly higher in the AC group than the AG group (21% vs 8%, p = 0.02). After propensity score-matching, 56 patients in each group remained for the outcomes analysis. We observed similar rates of 90-day mortality (6% vs 4%, p = 0.55), bacteremia relapse (0 patients in both cohorts), treatment failure (0% vs 1%, p = 0.50), and 90-day hospital readmission (24% vs 23%, p = 0.85) in the AC and AG-treated patient cohorts. Adverse events were more common in patients treated with AG, and more patients in the AG cohort switched antibiotic regimens than in the AC group.ConclusionEIE patients treated with AC have similar mortality rates as those treated with AG, while AG is associated with increased toxicity and adverse events. Larger, multi-center studies are still needed to compare the two antibiotic regimens.Disclosures All Authors: No reported disclosures

706. Impact of Infectious Disease Consultation on Management and Clinical Outcomes of Infective Endocarditis: Results of an interrupted time series analysis

BackgroundInfective endocarditis (IE) is associated with significant morbidity and mortality, and successful management requires expertise in both cardiac surgery and infectious disease (ID). However, the impact of ID consultation on clinical outcomes of IE is not clear.MethodsThe present study was a quasi-experimental, interrupted time series analysis of the clinical outcomes of patients with IE before (April 1998–April 2008) and after (May 2008–March 2019) the establishment of an ID department at a tertiary care hospital in Japan. The primary outcome was clinical failure within 90 days, defined as a composite of all-cause mortality, unplanned cardiac surgery, new-onset embolic events, and relapse of bacteremia caused by the original pathogen.ResultsOf 238 IE patients, 59 patients (25%) were treated in the pre-intervention period, and 179 patients (75%) were treated in the post-intervention period. Establishment of an ID department was associated with a 54% reduction in clinical failure (relative risk [RR], 0.46; 95% confidence interval [CI], 0.21–1.02; P=0.054) and a 79% reduction in new-onset embolic events (RR, 0.21; 95% CI, 0.07–0.71; P=0.01). In addition, the rate of inappropriate IE management significantly decreased (RR, 0.06; 95% CI, 0.02–0.22; P< 0.01).Segmented regression analysis for monthly rates of clinical failure. Table 1. Comparison of the clinical characteristics of the patients between the pre-intervention and post-intervention periods Table 2. Segmented regression analysis for primary and secondary outcomes ConclusionEstablishment of an ID department at a tertiary care hospital was associated with improved management, better clinical outcomes, and reduced embolic events in patients with IE admitted to the hospital.Disclosures All Authors: No reported disclosures

Impact of Infectious Disease Consultation on Management and Outcomes of Infective Endocarditis

Infective endocarditis (IE) is associated with significant morbidity and mortality, and successful management requires expertise in both cardiac surgery and infectious disease (ID). However, the impact of ID consultation on the clinical outcomes of IE is not clear. The present study was a quasi-experimental, interrupted time series analysis of the clinical outcomes of patients with IE before (April 1998-April 2008) and after (May 2008-March 2019) the establishment of an ID department at a tertiary care hospital in Japan. The primary outcome was clinical failure within 90 days, defined as a composite of all-cause mortality, unplanned cardiac operation, new-onset embolic events, and relapse of bacteremia caused by the original pathogen. Of 238 IE patients, 59 (25%) were treated in the preintervention period, and 179 (75%) were treated in the postintervention period. Establishment of an ID department was associated with a 54% reduction in clinical failure (relative risk, 0.46; 95% confidence interval, 0.21-1.02; P= .054) and a 79% reduction in new-onset embolic events (relative risk, 0.21; 95% confidence interval, 0.07-0.71; P= .01). In addition, the rate of inappropriate IE management significantly decreased (relative risk, 0.06; 95% confidence interval, 0.02-0.22; P < .01). Establishment of an ID department at a tertiary care hospital was associated with improved management, better clinical outcomes, and reduced embolic events in patients with IE admitted to the hospital.

Combination of Vancomycin or Daptomycin and Beta‐lactam Antibiotics: A Meta‐analysis

Observational and randomized controlled trials of the combination of vancomycin or daptomycin with a beta-lactam (BL) in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia have shown conflicting results on patient outcomes. The primary purpose of this meta-analysis was to compare clinical failure with the combination of vancomycin or daptomycin with a BL versus vancomycin or daptomycin monotherapy in MRSA bacteremia or endocarditis. A systematic literature search of PubMed, Embase, CINAHL, and meeting proceedings was conducted from inception through February 11, 2020, to identify relevant studies. The primary outcome was clinical failure and secondary outcomes were mortality, nephrotoxicity, and bacteremia. The meta-analysis was performed using Comprehensive Meta Analysis (version 3.0) with a random effects model. Outcomes were reported as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Nine studies of 1636 patients receiving vancomycin or daptomycin monotherapy versus the combination of vancomycin or daptomycin plus BL for MRSA bacteremia were included. Results showed combination therapy was associated with significantly lower clinical failure rates (OR 0.56, 95% CI 0.39-0.79, I2 =26.22%, p=0.001). Improvement in clinical failure was driven by lower rates of bacteremia relapse and persistence. However, no difference was seen with mortality. Combination therapy with vancomycin or daptomycin plus BL for MRSA bacteremia showed lower clinical failure rates, however, no significant difference was seen in mortality.

Accelerated treatment of endocarditis—The POET II trial: Rationale and design of a randomized controlled trial

The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to 6 weeks for patients with left-sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE, and complications to long hospital stays challenge the rationale for fixed treatment durations in all patients. The objective was to conduct a noninferiority randomized controlled trial (acronym POET II) investigating the safety of accelerated (shortened) antibiotic therapy as compared to standard duration in patients with left-sided IE. The POET II trial is a multicenter, multinational, open-label, noninferiority randomized controlled trial. Patients with definite left-sided IE due to Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis will be eligible for enrolment. Each patient will be randomized to accelerated antibiotic treatment or standard-length treatment (1:1) following clinical stabilization as defined by clinical parameters, laboratory values, and transesophageal echocardiography findings. Accelerated treatment will be between 2 and 4 weeks, whereas standard-length treatment will be between 4 and 6 weeks, depending on microbiologic etiology, complications, need for valve surgery, and prosthetic versus native valve endocarditis. The primary outcome is a composite of all-cause mortality, unplanned cardiac surgery, relapse of bacteremia, or embolization within 6 months of randomization. The POET II trial will investigate the safety of accelerated antibiotic therapy for patients with left-sided IE caused by Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis. The results of the POET II trial will improve the evidence base of treatment recommendations, and clinical practice may be altered.