bluuebunny/crossref_metadata_2025_split huggingface dataset:
219. Outcomes with Low- vs. High-bioavailability Oral Antibiotics in Treatment of Uncomplicated Gram-Negative Bacteremia
Authors: Cubillos Ashley L , Chandler Elisabeth , Murphy Ian P , Castro Robert 
Published: December 2021

Abstract

Background
High-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.

Methods
This 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.

Results
Of 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).

Conclusion
No 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
220. The Treatment of Enterococcus Blood Stream Infections in Patients Receiving Extracorporeal Membrane Oxygenation
Authors: Marcus Joseph E , Sobieszcyk Michal , Barsoumian Alice E 
Published: December 2021

Abstract

Background
Background: Extracorporeal membrane oxygenation (ECMO) is a growing modality of life support that is subject to a high rate of nosocomial infections. There is a paucity of data to guide treatment for infections on ECMO, which can lead to vastly different practice patterns at different centers. This case series describes the outcomes of patients with Enterococcus bacteremia at a single center.

Methods
A retrospective chart review was performed on all patients who received ECMO support at a tertiary academic medical center with ECMO capabilities between October 2012 and May 2020 with positive blood cultures for Enterococcus species.

Results
A total of 10 patients had Enterococcus bacteremia during the study period with E. faecalis (n=7, 70%) more commonly than E. faecium (n=3, 30%). Infections occurred more often in men (n=6, 60%) than women (n=4, 40%) with median age 36 (IQR: 31-42). Infections occured late in the hospitalization (median: 33 days (IQR: 26-59)) and after several weeks on the ECMO circuit (median: 24 days (22-52)). Infections were often polymicrobial (n=5, 50%). There were no cases of infective endocarditis. Infections were treated with 7-14 days of therapy with ampicillin being the most common antibiotic prescribed (n=5, 50%). Four (40%) patients were decannulated before completion of therapy. No patients had cannulas removed due to bacteremia. There were no cases of recurrence. Mortality was 20% in this cohort.
Clinical Characteristics of Patients with Enterococcus Bacteremia

Conclusion
Enterococcus is a common cause of blood stream infections in patients with prolonged courses on ECMO circuit. In this cohort of patients, Enterococcus did not cause any metastatic infections and was generally treated with 7-14 days of antibiotics without recurrence, despite many patients remaining on ECMO for extended periods after clearance. As ECMO use continues to expand, there will need to be more data on treatment outcomes of infections to establish best practices.

Disclosures
All Authors: No reported disclosures
221. Evaluation of Rates of Culture Positive Blood Stream Pathogens Prior to and During the SARS-CoV-2 Pandemic: A Multicenter Evaluation
Authors: Puzniak Laura A , Bauer Karri A , Yu Kalvin , Moise Pamela , Gupta Vikas 
Published: December 2021

Abstract

Background
Bacterial co-infections or super-infections are well-characterized complications of viral infections, further increasing morbidity and mortality of global viral pandemics. We evaluated trends in the incidence of culture positive gram-negative (GN), gram-positive (GP), and fungal/yeast pathogens from a blood source in hospitalized patients at US hospitals before and during the SARS-CoV-2 pandemic.
Table: Incidence and rate of blood pathogens in the pre and post SARS-CoV-2 period.

Gray indicates significantly lower rate compared to pre-pandemic time period, black indicates significantly higher rates compared to pre-pandemic.
Methods: This was a multi-center, retrospective cohort analysis of all hospitalized patients from 267 US acute care facilities with &gt;1-day inpatient admission between 7/1/19-5/19/21 (BD Insights Research Database [Becton, Dickinson and Company, Franklin Lakes, NJ]). SARS-CoV-2 infection was identified by a positive PCR during or ≤7 days prior to hospitalization. All admissions with a non-contaminant culture positive GN, GP, and fungal/yeast pathogen from a blood source were evaluated prior to and during the SARS-CoV-2 pandemic as rates per 1,000 admissions (p&lt; .05 for significance).

Results
There were 2,001,793 admissions in the pre-SARS-CoV-2 period (7/2019-2/2020) and 2,875,219 admissions during the SARS-CoV-2 pandemic. Incidence of GN/GP blood stream pathogens was significantly higher prior to the SARS-CoV-2 pandemic than during the pandemic. Higher rates of blood stream pathogens occurred in those who were tested for SARS-CoV-2, but all non-tested patients had significantly lower rates than pre-pandemic. Rates of Candida spp., Enterococcus spp., Serratia marcescens, and Enterobacter cloacae were higher in SARS-CoV-2 positive patients compared to pre-pandemic patients. Compared to the prior pandemic period, the incidence of B. fragilis, Streptococcus, Enterococcus and Candida were higher among those tested for SARS-CoV-2 but were negative.

Conclusion
In general, rates of positive blood cultures for bacterial pathogens were either lower or similar during the SARS-CoV-2 period compared to the pre-SARS-CoV-2 pandemic period. The patients that were tested for SARS-CoV-2 but were positive who had higher rates of infection than prior may indicate the similarity in viral and bacterial clinical presentation. Further evaluation of higher rates of Enterococcus and Candida in the pandemic period are warranted.

Disclosures
Laura A. Puzniak, PhD, Merck & Co., Inc. (Employee) Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kalvin Yu, MD, BD (Employee) Pamela Moise, PharmD, Merck (Employee) Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)
223. The Value of Neutrophil to Lymphocyte Count Ratio for Predicting the Clinical Outcomes of Patients with Carbapenem-resistant Klebsiella pneumonia Blood Stream Infection
Authors: Wu Heng 
Published: December 2021

Abstract

Background
The neutrophil to lymphocyte count ratio (NLR) has been recognized as a useful marker of inflammation. But, the prognostic function of NLR in patients with Carbapenem-resistant Klebsiella pneumonia (CRKP) blood stream infection is still largely unknown. The aim of this study was to explore the relationship between postoperative NLR and mortality in those patients.

Methods
We performed a retrospective study based on the database from Computerized Patient Record System in Sir Run Run Shaw Hospital from 1/1/2017 to 31/10/2020. Logistic analysis was performed to assess the associations between NLR and 28-day mortality. Multivariate analyses were used to control for confounders.

Results
A total of 134 CRKP blood stream infection inpatients were included in this study, including 54 fatal cases and 80 survival cases on the 28-day after the onset of CRKP BSI, the overall 28-day mortality rate of patients with a CRKP BSI episode was 40.3% (54/134). We conducted a multivariate analysis on these 134 patients and found that APACHE II score on the 4th day (OR 1.379 95% CI 1.065- 1.785, p = 0.015), NLR on the 4th day (OR 1.134 95% CI 1.054- 1.221, p = 0.001) were significant risk factors for the 28-day mortality of CRKP BSI patients

Conclusion
Elevated NLR was significantly associated with increased 28-day mortality as well as APACHE II score on the 4th day after first positive culture.NLR is promising to be a readily available and independent prognostic biomarker for patients with CRKP blood stream infection.

Disclosures
All Authors: No reported disclosures
224. Evaluating the Epidemiology of Bloodstream Infections: A Population-Based Study
Authors: Niazi Elaha , Mponponsuo Kwadwo , Somayaji Ranjani , Rennert-May Elissa , Conly John , Gregson Dan , Leal Jenine 
Published: December 2021

Abstract

Background
Bloodstream infections (BSI) are a major cause of morbidity, mortality, and health care costs worldwide. Population-based studies are key to assess BSI epidemiology over time while minimizing selection bias but remain limited. Therefore, we aimed to assess the incidence of BSI in a large Canadian health region in a contemporary period. We hypothesized that there would be significant age and sex-based differences including over time.

Methods
We conducted a retrospective cohort study from 2011 through 2018 using a population-based microbiology database to determine the annual age- and sex-specific BSI testing and case rates with the census as the population reference. BSI was defined as a positive blood culture for a pathogen. Episodes &gt; 30 days apart were included for analysis. Incidence rate ratios (IRR) for testing and case rates including by sex were calculated to assess changes over time. All analyses were run at a two-sided α of 0.05 and were conducted with R 4.0.4.

Results
A total of 154,147 distinct individuals (49.9% male) were analyzed and 22,869 (14.8%) had a BSI at the first encounter in the study period. Overall BSI testing incidence ranged from 1529 to 1707 per 100,000 person-years and case incidence ranged from 180 to 292 per 100,000 person-years. Testing and case incidence for BSI was greatest in the 0-4 and 75+ years age groups (p &lt; 0.01). Males compared to females had greater testing and case incidence rates in young and old age groups, but females had greater rates in the 15-44 years groups (p &lt; 0.01). Overall IRR for cases comparing 2018 to 2011 was 0.62 (95% CI 0.59-0.65) reflecting a significant decrease over time. Testing also decreased over the study period with an IRR of 0.90 (95% CI 0.88-0.91). Testing and case IRRs were not significantly different stratified by sex.
Incidence rates (per 100,000 person-years) of BSI testing and cases by sex from 2011 through 2018 in a Canadian health region

Conclusion
In our large population-based study of BSI, we identified that BSI remain frequent and the youngest and oldest age groups as well as males in these age groups have the greatest BSI incidence rates which may reflect both biological sex and gender-based differences. Encouragingly, BSI incidence rates have decreased over time at a greater increment relative to testing rates. Future studies of BSI should focus on pathogen and outcome-based evaluations.

Disclosures
All Authors: No reported disclosures
225. Risk Factors for Mortality in Stenotrophomonas Bacteremia: A Retrospective Study
Authors: Huang Glen , Davis Matthew R , Allyn Paul R 
Published: December 2021

Abstract

Background
Stenotrophomonas is a gram-negative organism typically associated with nosocomial infections. It is an emerging multi-drug resistant pathogen associated with significant morbidity and mortality in hospitalized patients. Optimal therapy is unknown. In this study, we evaluated the impact of treatment agent, dosing regimen, and patient characteristics on 30-day mortality for Stenotrophomonas bacteremia in our hospital system.

Methods
Retrospective chart review from April 2013 to September 2019 at Ronald Reagan and Santa Monica UCLA Medical Centers in Los Angeles, California. Adult patients who were hospitalized and received active therapy for Stenotrophomonas bacteremia were included in the study. Chi-square or Fischer test was used for categorical variables, Student’s t-test or Mann-Whitney U test was used for continuous variables.

Results
Sixty-nine patients were included in the study. The median age was 53 and 31 patients (44.9%) were female. Central line associated infections were the most common source of infection (79.7%, n = 55). Two patients (3%) had a relapse of infection. The overall 30-day mortality was 30.4% (n=21). The patients who did not survive to 30 days tended to have a higher Pitt bacteremia score, a longer length of stay, and were more likely to have used other antibiotics in the 30 days prior to culture collection. Trimethoprim-sulfamethoxazole (TMP-SMX) was the most common antibiotic used for treatment (n = 45, 65.2%). Of the patients who were treated with TMP-SMX, 19 were treated with high-dose (defined as 15 mg/kg or equivalent) and 26 had an alternative dosage after adjusting for renal function. There was no difference in 30-day mortality in the TMP-SMX high dose vs alternative dose (42.1% vs 30.8%, p = 0.53).

Conclusion
Stenotrophomonas bacteremia was associated with high mortality. High-dose TMP-SMX did not impact survival in our study; however, this may be due to small sample size. More research is needed to determine optimal therapy.

Disclosures
All Authors: No reported disclosures
226. Multidrug Resistant Polymicrobial Gram-negative Bacteremia in Hematologic Cancer Patients with Febrile Neutropenia at the Uganda Cancer Institute
Authors: Lubwama Margaret , Bwanga Freddie , Kateete David , Adams Scott , Namubiru Betty , Nabiryo Barbara , Orem Jackson , Phipps Warren 
Published: December 2021

Abstract

Background
Bloodstream infections (BSI) are associated with significant mortality in hematologic cancer patients with febrile neutropenia. Poor clinical outcomes are associated with presence of multidrug resistant (MDR) organisms and polymicrobial infections. We sought to determine antimicrobial resistance and outcomes of polymicrobial bloodstream infections in hematologic cancer patients with febrile neutropenic episodes (FNEs) at the Uganda Cancer Institute.

Methods
Blood drawn from participants during an FNE (fever ≥ 37.5°C and neutrophil count ≤ 1000 cells/µL) was cultured in the BACTEC 9120 blood culture system. Bacteria from positive cultures were identified biochemically. Antimicrobial susceptibility testing was performed with the disc diffusion method. Participants were followed for 30 days from first FNE onset for death from any cause. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%).

Results
Six hundred and twenty-nine participants were followed for FNE. Two hundred and twenty-eight FNEs in 159 participants were observed. Of 181 FNEs with blood cultures completed, 65 (36%) had pathogenic organism isolated. A total of 74 Gram negative and 18 Gram positive bacteria were isolated. Forty-eight (74%) FNEs had monomicrobial (MBSI) and 17 (26%) had polymicrobial (PBSI) bloodstream infections. Gram negative - Gram negative (10 out of 17, 59%) was the most frequent PBSI combination (Fig 1). Up to 75% (12 out of 16) of Gram-negative PBSI were MDR. The most common organism isolated was E. coli (38% of isolates). Participants with PBSI had higher early mortality rates at 7 days compared to MBSI and negative cultures (44%, 22%, and 16% for PBSI, MBSI, and negative respectively; HR (95% CI): 3.63 (1.49, 8.86) for PBSI v. negative/MBSI cultures). Similarly, PBSI was associated with higher mortality within 30 days of FNE onset (63%, 52%, and 38% for PBSI, MBSI, and negative respectively; HR (95% CI): 2.17 (1.09, 4.32) for PBSI v. negative/MBSI) (Fig 2).
Figure 1. Bar graph showing combinations for polymicrobial bloodstream infections (PBSI). GNGN: Gram-negative – Gram-negative; GNGP: Gram-negative – Gram-positive; GNO: Gram-negative – Other (fungi); GPGP: Gram-positive – Gram-positive

Figure 2. Kaplan-Meier failure curves of participants with negative cultures, monomicrobial infections and polymicrobial infections

Conclusion
PBSI episodes were more likely to be multidrug resistant and are associated with higher mortality. Empirical therapy for patients with PBSI should consider multidrug resistant Gram-negative bacteria

Disclosures
All Authors: No reported disclosures
231. Retrospective Comparison of Intravenous Therapy, Oral Therapy, and Lipoglycopeptides for the Treatment of Osteomyelitis
Authors: Stumphauzer Alex , Moenster Ryan P , Linneman Travis W 
Published: December 2021

Abstract

Background
The use of oral (PO) antibiotics and lipoglycopeptides are challenging the previous standard of osteomyelitis (OM) treatment, but there is currently a paucity of comparative data between these approaches.

Methods
This retrospective study included patients diagnosed with OM treated with intravenous (IV) antibiotics, PO antibiotics, or lipoglycopeptides between January 1, 2010 and June 1, 2020. Patients in the PO group could receive no more than 14 days of IV antibiotics prior to the PO course, and inclusion into the lipoglycopeptide group required at least 2 doses of drug to be administered. The primary outcome was occurrence of clinical failure within six months of completion of therapy, which was defined as new antibiotics or unplanned surgical intervention for an infection at the same site. Secondary outcomes included in-hospital length of stay (LOS), amputation within 6 months of therapy completion, and incidence of drug and line-related adverse effects. Previous osteomyelitis at index site, surgical intervention as a part of initial management, presence of Staphylococcus aureus on culture, utilization of outpatient parenteral antibiotic therapy (OPAT) services (IV group only), and concomitant PO therapy (lipoglycopeptide group only) were included in a bivariate analysis and variables with a p-value &lt; 0.2 were included in a multivariate regression model.

Results
The IV group included 257 patients, while the PO and lipoglycopeptide groups included 20 and 15 patients respectively. In the IV group, 89 (35%) of the patients experienced clinical treatment failure compared to 5 (25%) in the PO group and 5 (33%) in the lipoglycopeptide group (p=0.71). Median LOS was significantly shorter in the PO group compared to the IV and LGP groups [1 day (IQR 0-2.5) vs. 7 days (IQR 4-10) and 4 days (IQR 4-9), p=0.003]. No difference between groups was observed for amputation within 6 months or incidence of adverse effects. The only variable included in the multivariate regression model was previous osteomyelitis at index site [OR 1.75, 95% CI (1.07 – 2.87)].

Conclusion
PO and lipoglycopeptide therapy resulted in similar outcomes compared to IV antibiotics. Only previous OM at the same site was identified as an independent risk factor for failure.

Disclosures
Ryan P. Moenster, Pharm.D., FIDSA, AbbVie (Speaker’s Bureau)Melinta (Consultant, Speaker’s Bureau)
232. Safety and Effectiveness of Intravenous to Oral De-escalation Compared to Continued Vancomycin Therapy in Orthopedic Infections
Authors: Gallagher Chanah , Benefield Russell J , Certain Laura 
Published: December 2021

Abstract

Background
The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial determined oral antibiotics administered during the first six weeks of therapy were non-inferior to parenteral antibiotics. There was no difference in the incidence of serious adverse effects. The objective of this study was to evaluate the safety and effectiveness of de-escalating to oral therapy compared to continuing parenteral vancomycin therapy in patients with orthopedic infections in a real-world setting.

Methods
We conducted a single-center, retrospective cohort study of patients discharged between April 1, 2018 and April 1, 2020 with an orthopedic infection, a prescription for at least four weeks of parenteral vancomycin, and documented follow-up. The primary outcome was incidence of adverse events defined as provider documentation of the event and changes to therapy. The secondary outcome was incidence of 6-month treatment failure defined as repeat surgical intervention or therapy escalation.

Results
One hundred fifty-seven patients were included. Twenty-nine (18.5%) patients were de-escalated to oral therapy. Three (10%) patients in the oral therapy group had an adverse event compared to 35 (27%) in the vancomycin group (p=0.058). Of the 35 patients with an adverse event in the vancomycin group, eight were due to parenteral access-related complications. Treatment failure occurred in three (10%) patients in the oral therapy group compared to 27 (21%) patients in the vancomycin group (p=0.29). Three (10%) patients in the oral therapy group had an unplanned readmission compared to 25 (20%) patients in the vancomycin group (p=0.24).
Baseline Characteristics, Unplanned Readmission Rates, and Incidence of Adverse Events and 6-Month Treatment Failure

Conclusion
Patients de-escalated to oral therapy had fewer adverse events and similar incidences of treatment failure compared to patients maintained on parenteral vancomycin. Switching to oral therapy avoids some adverse events related to parenteral access. Our results in an uncontrolled, real-world setting are consistent with the OVIVA trial. Though limited by sample size, our data indicate switching to oral therapy in patients with an orthopedic infection improves safety outcomes without compromising effectiveness compared to continued parenteral vancomycin therapy.

Disclosures
Russell J. Benefield, PharmD, Paratek Pharmaceuticals (Grant/Research Support)