bluuebunny/crossref_metadata_2025_split huggingface dataset:
245. The impact of patient safety report and sentinel events on the prescribing and practice habits of infectious disease physicians
Authors: Kollu Vidya S , Zaidi Zareen , Cho Jonathan J , Abbott Andrew , Archibald Lennox , Kalyatanda Gautam 
Published: January 2021

Abstract

Background
Adverse events associated with antimicrobials range from mild to severe and may cause distress or harm to patients, and anxiety for prescribers. The basic tenets of prescribing antimicrobials are based on knowledge of the disease, pharmacokinetics, and pharmacodynamics of the prescribed agent, and effectiveness of the therapy. Inappropriate prescribing can increase costs and may cause reactions or the emergence of resistance. There is a paucity of published data on the prescribing habits of physicians after a sentinel event or patient safety report. Thus, we carried out this study to ascertain whether patient safety reports and sentinel events influence physician antimicrobial prescribing practices

Methods
We invited Infectious Disease physicians at the University of Florida to participate in a survey of their perception of risks and prescribing habits after a sentinel event. Participants were interviewed using a standardized questionnaire. Data were analyzed using Epi Info statistical software. Thematic analyses were performed on the open-ended interview questions.

Results
Of 17 faculty and fellows who participated in the survey, 5 (29.4%) had been practicing infectious disease for 1–3 years, 3 (17.6%) for 4–6 years, 2 (11.7%) for 7–9 years, and 7 (41.1 %) for &gt;nine years. Two (11.7%) had a patient safety report filed against them. All participants had experienced at least one sentinel event involving an antimicrobial agent. Sixteen (94%) changed their practice after sentinel events; 8 (47%) increased the frequency of ordering laboratory tests, and 7 (41%) indicated they might change to more expensive antimicrobials with better safety profiles. Eight (47%) participants endorsed hypervigilance when using antibiotics

Conclusion
We found that sentinel events affect physicians’ prescribing practices and monitoring of antimicrobial therapy. The most frequent changes included closer follow-up and obtaining more laboratory tests. However, some participants avoided certain antimicrobial agents or used more expensive therapies with better safety profiles. Although physicians use evidence-based medicine to alter their prescribing habits, serious adverse events can have an impact on the way we practice

Disclosures
Jonathan J. Cho, MD, Novartis (Shareholder)
255. Ticagrelor Aids Platelet-Mediated Clearance in a Refractory Staphylococcus aureus Endovascular Infection with Septic Emboli
Authors: Ulloa Erlinda , Uchiyama Satoshi , Nizet Victor , Sakoulas George 
Published: January 2021

Abstract

Background
The pore-forming alpha-toxin produced by Staphylococcus aureus (SA) decreases the viability and increases the clearance of platelets, a critical element of innate immune defense in endovascular infection. Our group recently identified that ticagrelor (TICA) blocks alpha-toxin-induced platelet clearance, protecting mice in a lethal systemic SA infection model. Here, we describe a case report in which TICA, added to antimicrobial therapy of a persistent methicillin-susceptible SA (MSSA) bacteremia associated with a septic aortic thrombus, resulted in immediate bacteremia clearance. We further explore TICA synergy with antibiotics and human platelets in vitro.

Methods
Antibiotic susceptibility of an MSSA strain from a patient treated with TICA for refractory bacteremia was tested by MIC and checkerboard assays in MHB or RPMI at standard (105 CFU/mL) or high (107 CFU/mL) inocula using TICA, ertapenem (ETP), cefazolin (CZ), or nafcillin (NAF) alone vs. ETP+CZ ± TICA. Killing assays with human platelets ± TICA against SA were also performed.

Results
SA bacteremia secondary to a septic aortic thrombus (&gt;4 mm) with multiple secondary pyogenic foci refractory to standard CZ and subsequent salvage CZ+ETP for 5 days rapidly cleared within 24 h after the addition of TICA. Thrombocytopenia resolved concurrently. Discontinuation of TICA on day 12 led to rebound thrombocytopenia, and TICA was restarted, once again resulting in resolution of thrombocytopenia. TICA alone lacked in vitro activity against SA, nor was TICA synergistic with ETP+CZ. In contrast, addition of a physiological achievable concentration of TICA dramatically sensitized SA to human platelet killing (p&lt; 0.001) in vitro.
Figure 1

Figure 2

Figure 3

Conclusion
In a complex case of aortic plaque rupture with septic thrombus, multiple septic emboli, and refractory MSSA bacteremia, addition of TICA to antimicrobial therapy yielded unanticipated immediate clinical and microbiological success. The profound therapeutic effect of TICA in vivo was corroborated by the enhanced staphylocidal activity of human platelets in vitro in the presence of physiological concentrations of the antiplatelet agent. TICA warrants further study as adjunctive treatment of refractory SA bacteremia due to a primary endovascular focus when thrombocytopenia is present.

Disclosures
Victor Nizet, MD, Centauri Therapeutics (Advisor or Review Panel member)Cidara Therapeutics (Advisor or Review Panel member)InhibRx (Advisor or Review Panel member)Roche Pharmaceutical (Advisor or Review Panel member)
258. A Comparison of Cefprozil and Fluoroquinolones for Gram-Negative Bacteremia
Authors: Nolen Rebecca C , Shor Emily M , Lucido Anthony , Hodges Georgeanne , Metzger Alex , Wu Julia , Unverferth James , Busch Lauren 
Published: January 2021

Abstract

Background
Beta lactams and fluoroquinolones (FQ) have been evaluated as step-down therapy options for Gram-negative bacteremia (GNB), but the preferred oral step-down antibiotic remains unclear.

Methods
This retrospective, non-inferiority, cohort study included adult patients who received oral step-down therapy with cefprozil or FQ (ciprofloxacin, levofloxacin) for GNB caused by Proteus spp, Klebsiella spp, or E. coli at SSM Health St. Louis between 1/1/2016 and 2/28/2020. The primary outcome was treatment failure, defined as all-cause mortality or recurrent infection within 30 days of initial bacteremia episode. Assuming an 85% success rate, to achieve 80% power with a noninferiority margin of 15%, 71 patients were required in each arm. Multivariate logistic regression was used to evaluate factors for treatment failure. Factors evaluated for inclusion in the multivariate model were oral antibiotic, age &gt;65 years, urinary source, Pitt bacteremia score &gt;2, ICU admission, and IV antibiotics for &gt;5 days prior to step-down.

Results
A total of 174 patients were included— 103 received cefprozil and 71 received FQ. Most baseline characteristics were similar between groups. Patients in the cefprozil group had more ICU admissions (21.3% vs. 7%; p=0.01), had a higher mean Pitt bacteremia score (1.6 vs 0.7; p&lt; 0.001), and received a longer duration (days) of IV antibiotics prior to step-down therapy (5.2 vs 4.1; p&lt; 0.001). Mean total treatment duration (days) was similar between groups (13.1 vs 13.2; p=0.75). Cefprozil 500 mg PO BID was administered in 84.5% of cefprozil patients. Treatment failure occurred in 3.88% (4/103) of cefprozil patients compared to 1.41% (1/71) of FQ patients (mean difference -2.47%; 95% CI -7.52% to 2.58%). The rate of adverse drug reactions was significantly higher in the FQ arm (2.9% vs 12.6%; p=0.016). In the univariate model, E. coli bacteremia, Pitt bacteremia score &gt;2, and IV antibiotic duration &gt;5 days met pre-defined criteria (p&lt; 0.2) for inclusion in the multivariate model. In the multivariate analysis, these factors were not found to be significant.

Conclusion
Cefprozil was non-inferior to FQ in regard to treatment failure. Cefprozil is an efficacious alternative to FQ for oral step-down treatment of GNB and was associated with significantly fewer adverse effects.

Disclosures
All Authors: No reported disclosures
259. A Prospective, Stewardship-Driven IV to PO Conversion in Uncomplicated Bacteremia
Authors: Quan Asia , Marks Gregory , Tran Hai P , Shane Rita , Ben-Aderet Michael , Sutterwala Fayyaz S , Grein Jonathan , Smith Ethan , Rapp Jeffrey 
Published: January 2021

Abstract

Background
Recent 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.

Methods
This 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.

Results
A 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.

Conclusion
Similar 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
260. A Rare Case of Severe Group B Streptococcal Infection with Toxic Shock-like Syndrome and Diffuse Metastatic Infection
Authors: Ayyash Ali M , Tran Ly , Ervin Charlie , Sampath Rahul , Campanile Teresa 
Published: January 2021

Abstract

Background
The incidence of invasive Group B streptococcal (GBS) infection has been increasing in the past decade and is currently at 10.9 cases per 100,000 population. GBS toxic shock-like syndrome is rare, with few cases reported over the past decade. The presumed etiology is the production of an uncharacterized pyrogenic toxin by certain strains.

Methods
We present a unique case of invasive GBS infection complicated by severe GBS-mediated toxic shock-like syndrome (TSLS) and diffuse metastatic infection.

Results
A 62-year-old obese male with diabetes mellitus presented with pain, swelling, and redness of the right shoulder and ankle for one week after a fall. Vitals were remarkable for tachycardia to 106 BPM and fever of 101°F with labs showing a leukocytosis to 23,500 u/L. The patient was started on ceftriaxone IV but continued to develop worsening fever, leukocytosis, encephalopathy, diffuse extremity pain, and whole-body macular erythema at 48 hours. Blood cultures grew GBS and TSLS was suspected. Adjunct clindamycin was started. MRI of the extremities demonstrated abscesses of the right levator scapulae, posterior scalene, brachioradialis, and right ankle. MRI of the spine showed epidural abscesses at L3-L5 and septic arthritis of the spinal facets at L4-L5. Operative abscess removal with joint washouts were performed by neurosurgery and orthopedics, and the patient symptomatically improved within 2 weeks on IV ceftriaxone. He was subsequently continued on cefazolin for 10 weeks and did well at follow-up.
Right elbow showing a characteristic flat, macular erythema of toxic shock-like syndrome.

Left arm with macular erythema.

MRI showing spinal epidural abscesses at L3-L5 spinal levels (arrows).

Conclusion
Invasive metastatic Group B Streptococcus infection in non-pregnant adults presenting with TSLS is rare. To our knowledge, there has never been a case of GBS infection causing TSLS with rapidly developing florid metastatic infection including epidural abscess development, septic arthritis, and musculoskeletal abscesses. This case highlights the wide range of infectious possibilities associated with severe GBS infection.

Disclosures
All Authors: No reported disclosures
261. A Single-Center Case Series of Methicillin-Resistant S. aureus Bacteremia with Elevated Minimal Inhibitory Concentrations to Vancomycin
Authors: Mills Alexandra , Dupper Amy , Chacko Kieran , Nadkarni Devika , Caban Ana Berbel , Fox Lindsey , Obla Ajay , Van Bakel Harm , Altman Deena 
Published: January 2021

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) is a serious nosocomial pathogen, and is listed as a “High Priority Pathogen” by the WHO due to concerns of antimicrobial resistance and lack of novel therapeutics. Even in vancomycin-susceptible MRSA, increased rates of treatment failure occur in the setting of an increased minimum inhibitory concentration (MIC) to vancomycin, which is considered the gold-standard of therapy. We performed a case series of 25 patients infected with MRSA with an elevated MIC to vancomycin. Additionally, we describe the use of combination therapy with beta-lactams for the management of these highly complex cases.

Methods
We conducted a retrospective case series of 25 patients hospitalized at MSH between 8/2014–5/2019 who were treated for MRSA bacteremia where the isolate had an MIC ≥ 2. Data was centralized into the REDCap program. Clonal typing of bacteria and analysis of clinical features were performed in SAS and R.

Results
In total, 25 patients developed MRSA bacteremia with a vancomycin MIC ≥ 2. The majority of cases involved infection from vascular access, arteriovenous fistula/graft, and septic joint/osteomyelitis. All 25 patients were initially treated with vancomycin, with modification of therapy varying widely depending on clinician. The most common vancomycin-alternative was daptomycin (14/25 patients, alone and in combination). Combination therapy with vancomycin or daptomycin and a beta-lactam was used in 9 cases (36% of cases). Average number of days to clearance was 18.3 (range 1–69 days). Univariate and multivariate analyses revealed significant correlation MRSA bacteremia with vancomycin MIC ≥ 2 and admission from a nursing home or skilled nursing facility (p=0.02), history of MRSA colonization (p=0.006), and persistent bacteremia (bacteremia &gt;7 days)(p&lt; .0.001).

Conclusion
With few novel therapeutics under development, management of MRSA bacteremia with a rising MIC to vancomycin is a clinical challenge for practitioners. In our case series we found that treatment is largely patient and practitioner-dependent, and far from standardized. Further definition of the clinical risk factors for development and novel therapeutic strategies will enable understanding of how to best manage these challenging infections.

Disclosures
All Authors: No reported disclosures
263. An Evaluation of Quality Indicators for the Management of Staphylococcus aureus Bacteremia: A Nested Case-Control Study
Authors: Simms Andrew , Schweizer Marin L , Ohl Michael , Perencevich Eli N , Goto Michihiko 
Published: January 2021

Abstract

Background
Community-acquired Staphylococcus aureus bacteremia (CA SAB) is a common infection with high mortality. Ten Oever et al. recently used expert consensus methods to develop a set of 25 quality indicators for SAB care in five domains (i.e., follow up blood cultures, echocardiography, non-antibiotic interventions including source control, antibiotic treatment, and other management aspects). Associations between these quality indicators and patient outcomes have not been evaluated. We assessed associations between proposed quality indicators and all-cause 30-day mortality among patients with CA SAB.

Methods
We conducted a nested case-control study within a described national multicenter cohort of patients with SAB in the Veterans Health Administration (VHA). The cohort included 2,093 patients who were: 1) admitted to acute care hospitals between 1/2012 and 12/2014 for CA SAB (the first positive blood culture before or within 48 hours of admission with no recent healthcare exposure); 2) survived at least 96 hours after the SAB onset. We identified paired cases (who died within 30 days) and controls (who survived an equal time), matched 1:1 for age (+/- 5 years), gender, admission year and month, and methicillin susceptibility of isolates. We reviewed charts to extract information for quality indicators. We estimated associations between quality indicators and mortality using logistic regression, adjusting for patient demographics and comorbidity.

Results
164 patients (82 cases and 82 controls) were included. The median patient age was 68.5 (IQR: 62–80) years, and 74 (45.1%) had methicillin-resistant isolates. All patients received at least one domain of quality indicator (median: 3 [IQR: 2–4]). When analyzed individually, only two domains (follow-up blood cultures: OR 0.27 [95% CI: 0.11–0.68]; source control: OR: 0.13 [0.05–0.31]) were associated with mortality. There was a dose-response relationship in which more domains received was associated with decreased mortality (Figure).
Association Between the Number of Satisfied Quality Indicator Domains and All-Cause 30-day Mortality

Conclusion
Among patients with CA-SAB, the number of satisfied quality indicator domains was associated with 30-day mortality with a dose-response relationship. This finding supports the relevance of these quality indicators for SAB management.

Disclosures
All Authors: No reported disclosures
264. Anti-platelet Therapy Significantly Reduces Inpatient Mortality in Patients with Staphylococcus aureus Bacteremia
Authors: Caffrey Aisling , O’Neill Emily T , Lopes Vrishali , Ulloa Erlinda R , Sakoulas George , Nizet Victor , LaPlante Kerry 
Published: January 2021

Abstract

Background
There is a growing body of evidence which suggests that P2Y12 inhibitors may have antibacterial properties in vivo. To our knowledge, this has not been previously examined using real world clinical data from patients with specific infections.

Methods
Our retrospective cohort study included patients admitted to Veterans Affairs hospitals between 2010–2018 with blood cultures positive for S. aureus and treated with appropriate antibiotics within 48 hours of culture collection. We included patients treated with P2Y12 inhibitors for at least the 30 days prior to admission and continued use for at least 5 days after admission. Non-users included patients without P2Y12 inhibitor use in the year prior to admission through discharge. We compared clinical outcomes during the S. aureus bacteremia admission among P2Y12 users and non-users using propensity score matched Cox proportional hazards regression models.

Results
We identified 371 P2Y12 inhibitor users (clopidogrel, prasugrel, ticagrelor, cangrelor) and 13,298 non-users. Mean age was 70 years and 69 years, respectively. Over 98% were male in both the groups, and the overall inpatient mortality rate was 8.7%. We were able to match 199 users and non-users, which were well matched in terms of baseline covariates. Inpatient mortality was significantly lower among P2Y12 inhibitor users (hazard ratio [HR] 0.08, 95% confidence interval [CI] 0.01–0.64), and 30-day mortality was non-significantly lower (HR 0.57, 95% CI 0.31–1.03). There was no difference between the groups in readmission or re-infection within 30 days of discharge.

Conclusion
Among patients with S. aureus bacteremia, those treated with P2Y12 inhibitors in the days leading up to admission and continuing through the initial period of antibiotic treatment, had a 92% lower risk of inpatient mortality. Identifying adjunctive therapies which improve clinical outcomes among patients with S. aureus bacteremia is highly important in order to improve patient outcomes and to increase the understanding of the pathophysiology of the disease. Prospective clinical studies are needed to further define the potential benefits of P2Y12 inhibitors in S. aureus bacteremia and possibly other infection types.

Disclosures
Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Erlinda R. Ulloa, MD, MSc, Cidara Therapeutics (Consultant) Victor Nizet, MD, Centauri Therapeutics (Advisor or Review Panel member)Cidara Therapeutics (Advisor or Review Panel member)InhibRx (Advisor or Review Panel member)Roche Pharmaceutical (Advisor or Review Panel member) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)
267. Characteristics and Trends of Serratia Blood Stream Infections
Authors: Elabd Hatem , Eagleston Anjuli , Brandt Dominique , Blatt Stephen 
Published: January 2021

Abstract

Background
Serratia is an opportunistic pathogen known to cause an array of infectious presentations including UTIs, pneumonia, wound infections, skin and soft tissue infections, surgical site infections and although rare, endocarditis and bacteremia. The aim of the proposed study is to identify the characteristics of patients with community-acquired Serratia blood stream infection over a five-year period within the TriHealth inpatient population within the Cincinnati, Ohio Region. The study will also examine antibiotic resistance patterns among patients with Serratia bloodstream infections.

Methods
This is a retrospective cohort study of 107 adult patients admitted to two community hospitals from January 2014 to December 2018 with a positive blood culture for Serratia species. A complete data set of 100 patients was analyzed for complications, antibiotic resistance, in-hospital mortality, 90-day mortality, readmission within 90 days and length of Hospital Stay (LOS). Descriptive statistics was performed using frequencies for discrete variables and median (IQR) for continuous variables.

Results
Patients admitted with a positive Serratia blood culture were 38% female with a median (IQR) age of 54.5 years (40.25–71.75) and predominantly white (85%). Forty percent had hepatitis C (HCV) infection and 42% had a history of IV drug use. Most patients were living at home (77%), 18% in long term care and 91% were infected with Serratia marcescens. The most common complications were endocarditis (12%) and osteomyelitis (10%). Extended spectrum beta-lactamase (ESBL) production was confirmed in 13%. In-hospital mortality was 2%, 90-day mortality 2%, readmission 23% and median (IQR) LOS 7(3.25–14.75).
PATIENT CHARACTERISTICS AND OUTCOMES (part 1)

PATIENT CHARACTERISTICS AND OUTCOMES (part 2)

PATIENT CHARACTERISTICS AND OUTCOMES (part 3)

Conclusion
This study demonstrates that a high proportion of patients admitted with Serratia bacteremia are IV drugs users and that they have a high prevalence of coexistent HCV infection. Endocarditis and metastatic foci of infection are relatively common. Appropriate empiric antibiotic management should take into account the significant incidence of ESBL production resulting in a prolonged LOS and a high readmission rate.

Disclosures
All Authors: No reported disclosures