bluuebunny/crossref_metadata_2025_split huggingface dataset:
256. Serratia Marcescens Bacteremia and Endocarditis: A Treatment Assessment from an Academic Medical Center
Authors: Slain Douglas , Howard Catessa , Cooper Clinton G 
Published: January 2021

Abstract

Background
Serratia Marcescens (SM) is often an opportunist that has been associated as a cause of healthcare-associated infection and in some people who inject drugs (PWID). Decisions about the treatment of SM infections are difficult given the small clinical studies available and concerns for multidrug resistance. SM has the ability to produce inducible AmpC b-lactamase and may acquire extended-spectrum b-lactamase (ESBL). Evidence-based guidance is lacking in terms of identifying preferred antimicrobial therapy of SM bacteremia and endocarditis. Compared to other reports, our hospital has one of the largest SM data sets to compare.

Methods
This observation study included adult patients admitted to our hospital (2016–2019) with SM bloodstream infections, including endocarditis. Patients were excluded from the analysis, if they had a concomitant infection with another gram-negative organism. Our evaluation was designed to: compare outcomes associated with different antibiotic regimens, evaluate how care differed in PWID patients versus others, and identify factors associated with obtaining infectious diseases expert consultations (ID Consult).

Results
Forty-three patients met study inclusion/exclusion. Twenty-eight patients (65.1%) had ID Consults. Twenty-four (55.8%) were PWID. Endocarditis was diagnosed in 30.2% of patients. The most common regimen was cefepime +/- aminoglycoside, followed by a carbapenem +/- aminoglycoside. Combination therapy was only recommended during ID Consult. Piperacillin-tazobactam was used in 11.6% of patients. No regimen displayed an efficacy or safety advantage over another. Most patients (90.7%) cleared their blood stream within 48 hours of antibiotic start. Phenotypic susceptibility testing did not identify either ESBL or AmpC production in any of the isolates, including recurrences. Multi-drug resistance was not appreciated. Significant factors associated with obtaining ID Consult were: PWID (p=0.004), endocarditis (p=0.0002), sepsis (p=0.022), surgical intervention (p=0.003).

Conclusion
We could not identify an advantage with any particular antibiotic treatment regimen in this study. Induction of AmpC or selection of ESBL organisms was not displayed by any of the organisms.

Disclosures
All Authors: No reported disclosures
257. Staphylococcus aureus Bacteremia: Does Intravenous Drug Use Impact Quality of Care and Clinical Outcomes?
Authors: McClellan Kristen , Hilsendager Cami , Luke Strnad 
Published: January 2021

Abstract

Background
Individuals with intravenous drug use (IDU) have higher risk for Staphylococcus aureus bacteremia (SAB) and increased management complexity. The goal of this study was to compare differences in SAB characteristics, adherence to standard of care metrics, and clinical outcomes in those with and without IDU.

Methods
A retrospective chart review was conducted on cases of SAB between January 1, 2016 and December 31, 2017 at a 500-bed teaching hospital. Inclusion criteria was age &gt; 18 years and ≥ one blood culture positive for S. aureus. Patients were excluded if they transferred hospitals, had care withdrawn or died within 48 hours of diagnosis or had a ventricular assist device infection. Records were reviewed for substance use, SAB characteristics, standards of care, and outcomes. Data were analyzed using SPSS software. The study was approved by the Institutional Review Board.

Results
In 248 patients with SAB, 28.2% had documented IDU. Median age was 37 (IDU) and 57 (non-IDU). In the IDU group, 75.7% had the formal diagnosis of opioid use disorder and 78.9% of stimulant use disorder. IDU was associated with hepatitis C and houselessness while non-IDU was associated with diabetes, hemodialysis, and cancer. Those with IDU had higher rates of MRSA, endocarditis, and spinal infections, but did not have higher rates of polymicrobial infections or venous thrombosis. There was no difference in appropriate repeat blood cultures, antibiotic management, and ID consultation. Length of stay and against medical advice (AMA) discharges were higher in those with IDU. There was no difference in 90-day recurrence or readmission, but 90-day mortality was higher in the non-IDU group.

Conclusion
There was no difference in adherence to SAB quality of care metrics between groups with and without IDU. Despite the IDU group being younger with fewer comorbidities, 90-day readmissions were not different between groups. This bears further analysis but may represent the influence of therapy completion, AMA discharges, and unmeasured social determinants of health.

Disclosures
All Authors: No reported disclosures
262. A Systematic Review and Meta-Analysis of the Impact of Delayed Appropriate Antibiotic Therapy on Mortality in Patients with Gram-Positive Bacteremia
Authors: Liu Steve , Moua Paochee , Monjor Selam , Zasowski Evan J 
Published: January 2021

Abstract

Background
Antibiotic resistance is common and frequently leads to unintentional delays in appropriate antibiotic therapy. The detrimental impact of delayed therapy is well-accepted, but the majority of evidence focuses on gram-negative infections. A review and synthesis of the evidence evaluating the impact of delayed appropriate antibiotic therapy in serious gram-positive infections does not exist. Such data would define the scope of the problem in this important patient population where antibiotic resistance is common. The objective of this systematic review and meta-analysis was to assess the impact of delayed appropriate antibiotic therapy on mortality in patients with gram-positive bacteremia.

Methods
Pubmed and Embase were searched from inception to March 30, 2020 to identify clinical studies of patients with bacteremia due to staphylococci, enterococci, or streptococci that reported the association between delayed appropriate antibiotic therapy and mortality. Three independent reviewers screened search results. Study quality was assessed via Newcastle-Ottawa Assessment Scale. Meta-analyses evaluating association between delayed therapy and mortality were conducted via random effects models in Review Manager 5.3. The primary analysis included unadjusted effect estimates from studies reporting unadjusted data. Secondary analysis included adjusted effect estimates from studies adjusting for confounding.

Results
Of 3684 search results, 16 cohort studies encompassing 4173 bacteremias were included. Ten studies involved S. aureus, 5 enterococci, and 2 S. pneumoniae. One-third (33.7%) of the 3659 patients in the primary analysis received delayed appropriate antibiotic therapy. The primary meta-analysis of 15 studies reporting unadjusted data showed a statistically significant association between delayed therapy and mortality (figure 1). Results from secondary analysis using adjusted point estimates from 9 studies were similar (figure 2).
Figure 1. Forrest plot of meta-analysis of unadjusted association between delayed therapy and mortality

Figure 2. Forrest plot of meta-analysis of covariate adjusted association between delayed therapy and mortality

Conclusion
Delayed appropriate therapy was common and associated with increased mortality in patients with gram-positive bacteremia. These findings underscore the need for continued antimicrobial stewardship efforts to ensure expeditious appropriate antibiotic therapy for patients with gram-positive bacteremia.

Disclosures
All Authors: No reported disclosures
268. Clinical Characteristics and Mortality Associated with Culture Positivity in Adult Inpatients with Sepsis: A 15-Year Cohort Study of 48,706 Patients at a Tertiary Medical Center in Taiwan
Authors: Chiang Hsiu-Yin , Chen Pei-Shan , Chi Chih-Yu , Kuo Chin-Chi 
Published: January 2021

Abstract

Background
Culture-negative (CN) sepsis occurs in 30~60% of sepsis patients. Understanding CN sepsis is crucial for treatment optimization. We used an electronic medical records (EMR)-based surveillance proposed by Rhee et al. to identify patients with sepsis meeting Sepsis-3. We aimed to describe the trend of sepsis and mortality, and to study the characteristics and mortality associated with culture positivity.

Methods
This cohort study included adult (&gt;=18 years) inpatients with first-time sepsis who were admitted to our hospital during 2003–2017 (Figure 1). Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction. Culture-positive (CP) sepsis were those whose blood grew non-commensal organisms for &gt; = 1 blood draw and those whose blood grew commensal organisms for &gt; = 2 blood draws. Mortality were ascertained by the National Cause of Death Database. Multivariable Cox proportional hazard model was used to evaluate the effect of culture positivity on all-cause mortality.
Figure 1. Selection Process of the Study Population (N = 48,706).

Results
Of 48,706 adult inpatients with first-time sepsis, 41,304 (84.8%) were CN. The sepsis rate increased from 4.6% to 8.7%, while in-hospital mortality significantly decreased from 30.2% to 14.5% (Figure 2). Patients with CN sepsis tended to be younger, male, less diabetes, liver cirrhosis but more cardiovascular disease, and received systemic antibiotic within 14 days prior (Table 1). Serum biochemical profiles of procalcitonin, hs-CRP, and lactate were significantly lower in CN sepsis. Mechanical ventilation and respiratory site of infection were more likely to be presented in CN sepsis. Overall, the mortality (in-hospital, 7-day, 30-day, 1-year) was lower in CN sepsis. After adjusting for confounders, culture positivity was significantly associated with 7-day mortality (aHR 1.21; 95% CI 1.08, 1.37) (Table 2).
Figure 2. The Trend of Sepsis Rate (A) and In-hospital Mortality (B) of Adult Inpatients with Sepsis, 2003–2017 at CMUH.

Table 1. Baseline Demographic and Clinical Characteristics of the Adult Inpatients with Sepsis, 2003–2017 at the CMUH (N = 48,706).

Table 2. Hazard Ratio (95% Confidence Interval) for Mortality Associated with Culture-Positive Sepsis.

Conclusion
Sepsis rate increased while the mortality decreased, indicating the improvement of sepsis management in the past 15 years. The clinical characteristics of CN and CP sepsis were comparable, except for the lower inflammatory markers found in CN sepsis. Patients with CP sepsis had 21% higher risk of 7-day mortality. Next, we will link with National Health Insurance Database to examine admission history and antibiotic use in other institutions.

Disclosures
All Authors: No reported disclosures
269. Clinical Characteristics and Outcomes of Persistent Staphylococcus aureus Bacteremia
Authors: Yang Eunmi , Chung Hyemin , Seo Hyeonji , Kim Haein , Kim Jinyeong , Park Sunghee , Sung Heungsup , Kim Mi-Na , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Woo Jun Hee , Kim Yang Soo 
Published: January 2021

Abstract

Background
Staphylococcus aureus bacteremia (SAB) is a leading cause of bacteremia and persistent SAB is associated with poor outcomes. We evaluated key clinical characteristics and outcomes associated with persistent SAB.

Methods
We reviewed patients enrolled in a prospective cohort of adult patients with S. aureus bacteremia at a tertiary hospital from August 2008 to December 2018. Clinical characteristics, outcomes, and microbiologic characteristics of patients with persistent bacteremia (≥ 3 d) were evaluated.

Results
Of the total 969 patients, 617 (63.7%) patients had persistent bacteremia. The median duration of bacteremia with persistent bacteremia was 5 days. The most common sources of persistent bacteremia were central venous catheter-related infection (33.4%) and bone and joint infection (14.9%). Methicillin resistant S. aureus (MRSA) isolates were analyzed in 372 (60.3%) patients and metastatic infections were 217 (35.2%) with persistent bacteremia. In the multivariate analysis, APACHE Ⅱ score (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 1.03–1.10), Charlson comorbidity index score (aOR, 1.14; 95% CI, 1.04–1.25), liver cirrhosis (aOR, 2.47; 95% CI, 1.44–4.23), and S. aureus pneumonia (aOR, 3.04; 95% CI, 1.29–7.18) were independently associated with 30-d mortality. In persistent MRSA bacteremia, ST5-SCCmecⅡ was 59.7% (222/372) and agr dysfunction was 64.8% (241/372). After adjusting for confounding factors, APACHE Ⅱ score (aOR, 1.08; 95% confidence interval [CI], 1.04–1.12), liver cirrhosis (aOR, 3.09; 95% CI, 1.56–6.14), and S. aureus pneumonia (aOR, 4.37; 95% CI, 1.40–13.67) were independently associated with 30-d mortality.
Table 1. Demographic and Clinical characteristics of Patients With Persistent Bacteremia

Table 2. Microbiologic Characteristics and Genotypes in MRSA Isolates Responsible for Persistent Bacteremia

Fig 1. Duration of Staphylococcus aureus bacteremia

Conclusion
In persistent bacteremia, clinical factors, including APACHE Ⅱ score, Charlson comorbidity index score, liver cirrhosis, and S. aureus pneumonia contribute to 30-d mortality.

Disclosures
All Authors: No reported disclosures
271. Clinical Outcomes Treating Gram-Negative Bacteremia with Oral Beta-Lactams vs. Trimethoprim-Sulfamethoxazole or Fluoroquinolone Step-Down Therapy
Authors: Sinclair Emily , Frens Jeremy J , Zeigler Dustin , Mccarthy Megan , Sharma Roopali 
Published: January 2021

Abstract

Background
Recently, studies about gram-negative bacteremia have shown that shorter courses and early step-down therapy with oral agents have equivalent outcomes compared to longer courses with intravenous therapy. The question remains, however, as to which oral agents may be most appropriate for oral conversion therapy. At Cone Health it has been common practice to de-escalate to oral beta-lactams due to local susceptibility patterns and safety concerns with fluoroquinolones. This study retrospectively evaluated the 30-day clinical outcomes of patients treated with oral beta-lactams as step-down therapy vs. fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX).

Methods
In this IRB approved, retrospective review, 200 patients with gram-negative rod bacteremia were screened. Sixty-seven patients were excluded due to inpatient mortality (17), transfer to another facility (7), hospice care (6), or receipt of intravenous antibiotics only (37). The most common organism isolated was E. coli at 57% (75/133) and a majority of cases had a genitourinary source, 79/133 (59%). The primary endpoints were 30-day readmission and mortality. Secondary endpoints included total length of antibiotic therapy and length of IV therapy.

Results
Of the 133 patients included, 101 (76%) received an oral beta-lactam and 32 (24%) received either a fluoroquinolone or TMP-SMX. In the beta-lactam group 22/101 (21.8%) were re-admitted within 30-days compared to 5/32 (15.6%) in the fluoroquinolone and TMP-SMX group (p=0.412). Each group had one patient re-admitted due to recurrence of bacteremia. The majority of patients in the beta-lactam group were re-admitted for a non-infectious reason (82%). Only 1 (1%) patient in the beta-lactam group died within 30 days of discharge compared to 2 (6%) in the fluoroquinolone group (p=0.165). Average total length of therapy in the beta-lactam group was 12.8 days compared to 14 days in the fluoroquinolone and TMP-SMX group (p=0.065). Average length of IV therapy was 3 days in the beta-lactam group and 4 days in the fluoroquinolone and TMP-SMX group (p=0.99).

Conclusion
At our institution, we have not noted any significant difference in 30-day bacteremia recurrence or mortality between those who receive oral beta-lactams or fluoroquinolones/TMP-SMX.

Disclosures
All Authors: No reported disclosures
272. Clinical Outcomes with Continuation of Combination Antibiotic Therapy versus De-escalation to Monotherapy for Patients with MRSA Bacteremia
Authors: Nichols Courtney , Sobhanie Mahdee , Wardlow Lynn , Coe Kelci E 
Published: January 2021

Abstract

Background
Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with increased morbidity and mortality. Previous studies have demonstrated lower mortality with combination therapy (CT) compared to monotherapy (MT) for MRSA bacteremia; however, there is a lack of evidence to favor continued CT over de-escalation to MT for completion of treatment after clearance of bacteremia.

Methods
This was a single-center, retrospective study at The Ohio State University Wexner Medical Center in patients with MRSA bacteremia from November 2011 to July 2019. The primary composite outcome included inpatient infection-related mortality, 60-day readmission and 60-day bacteremia recurrence in patients receiving daptomycin and ceftaroline CT for greater than 10 days against those who received three to ten days of CT and were then de-escalated to either daptomycin, ceftaroline, or vancomycin MT. Statistical analysis used simple and multivariate logistic regression models to estimate crude and adjusted odds ratios and the 95% confidence interval to assess the relationship between the composite outcome for the MT and CT groups, while controlling for proven cofounders.

Results
A total of 286 patients with MRSA bacteremia were identified with 146 patients omitted based on exclusion criteria. The study population included 66 in the CT group and 74 in the MT group. Of those in the MT group 20 received ceftaroline, 29 received daptomycin, and 25 received vancomycin. Median age was 46 years (IQR 34.5–61), 60% required intensive care unit stay (n=84), and patients were 51% female (n=71) and 78% white (n=109). Bacteremia source was primarily intravenous drug use (40%) or line-related (16%). No significant difference was observed in the primary composite outcome (21% CT group vs 24% MT group; p=0.66). Within this outcome, there was no significant difference in readmission within 60 days (20% CT group vs 18% MT group; p=0.75), bacteremia recurrence within 60 days (3% CT group vs 7% MT group; p=0.45), or inpatient infection-related mortality (2% CT group vs 5% MT group; p=1.00).

Conclusion
No significant difference was found in the composite clinical outcome for MRSA bacteremia patients with continued CT versus those who were switched to MT.

Disclosures
All Authors: No reported disclosures
274. Comparison of Cefazolin Susceptibilities of Enterobacterales with an Automated Susceptibility Testing Platform versus In Vitro Antimicrobial Testing
Authors: Noval Mandee , Heil Emily , Williams Paula , Johnson J Kristie , Claeys Kimberly C 
Published: January 2021

Abstract

Background
The Clinical and Laboratory Standards Institute (CLSI) revised breakpoints for cefazolin (CFZ) may be difficult to implement with current automated susceptibility testing (AST) platforms and Enterobacterales may be falsely reported as susceptible to CFZ. The possibility remains that CFZ may then be inappropriately used as definitive therapy.

Methods
This was a retrospective observational cohort of adult patients with Enterobacterales bloodstream infections (BSI) reported CFZ susceptible per Vitek®2 (bioMerieux, Durham NC). The primary outcome was the percentage of CFZ susceptible Enterobacterales isolates using three different susceptibility testing methods: Vitek®2 automated testing, ETEST® (bioMerieux, Durham NC), and disk diffusion. Secondary outcomes included treatment failure defined as a composite outcome of 30-day all-cause inpatient mortality, 30-day recurrent BSI, 60-day recurrent infection, or infectious complications.

Results
In 195 isolates reported CFZ susceptible per Vitek®2, 84 (43.1%) were CFZ susceptible using E-test vs.119 (61%) using disk diffusion (Figure 1). Rates of treatment failure were similar in both CFZ and non-CFZ groups (33.3% vs. 38.5% respectively; p=0.57). Both groups had high rates of ID consult involvement (&gt;60%) and source control (&gt;80%) with urinary tract being the most reported source. No difference was noted in 30-day all-cause mortality, secondary infectious complications, 30-day readmissions, or 60-day recurrent infections. A subgroup analysis of patients receiving CFZ vs. ceftriaxone suggests treatment failure was significantly less likely to occur in the setting of source control (adjusted OR 0.06; 95% CI, 0.13–0.32) and ID consult
Figure 1: CFZ Susceptibilities by Testing Method

Conclusion
There was a large discrepancy among testing methods; additional confirmatory CFZ susceptibility testing beyond AST platforms should be considered prior to definitive use of CFZ for systemic Enterobacterales infections.

Disclosures
All Authors: No reported disclosures
276. Comparison of Ceftaroline in Combination with Either Vancomycin or Daptomycin for the Treatment of Methicillin-resistant Staphylococcus aureus Bacteremia
Authors: Welch Stephanie N , Meredith Jacqueline , Roshdy Danya , Medaris Leigh A , McCurdy Lewis 
Published: January 2021

Abstract

Background
Recent studies have suggested that combination therapy may be preferred to monotherapy for select patients with methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B); however, direct comparison between various combination regimens is lacking.

Methods
This was a multicenter, retrospective cohort study evaluating adult patients with MRSA-B who received vancomycin/ceftaroline (VAN+CPT) or daptomycin/ceftaroline (DAP+CPT) for at least 48 hours between April 1, 2017 and June 30, 2019. Patients with primary respiratory or central nervous system infections were excluded. The primary endpoint was rate of clinical success, defined as survival at 90 days, sterilization of blood cultures within 96 hours of combination therapy initiation, no perceived clinical failure requiring a change in MRSA-active therapy, and absence of recurrence. Secondary endpoints included time to culture clearance from combination therapy initiation, 30-day and in-hospital mortality, adverse events prompting antibiotic discontinuation, and hospital and intensive care unit length of stay.

Results
A total of 54 patients were included in the VAN+CPT group and 25 patients in the DAP+CPT group. Baseline characteristics were generally similar between groups, except patients in the VAN+CPT group were younger and more likely to have endocarditis. Bone/joint sources were more common in the DAP+CPT group. Initiation of combination therapy occurred 104.9 hours vs 140.0 hours from index culture collection in the VAN+CPT and DAP+CPT groups, respectively. Rates of clinical success were similar between groups (63.0% vs 64.0%, p=0.93). Time to culture clearance from combination therapy initiation was 50.9 hours in the VAN+CPT group compared to 48.6 hours in DAP+CPT (p=0.83). Rates of nephrotoxicity were higher in those who received VAN+CPT (16.7% vs 0%, p=0.04). Other secondary endpoints were similar between groups.

Conclusion
Rates of clinical success were similar between groups, though there was a significantly higher rate of nephrotoxicity noted in the VAN+CPT group. Our study supports that clinical outcomes may be similar between VAN+CPT and DAP+CPT, with greater safety concerns associated with VAN+CPT.

Disclosures
All Authors: No reported disclosures