bluuebunny/crossref_metadata_2025 huggingface dataset:
273. Comparative Effectiveness of Ampicillin in the Treatment of Enterococcus faecalis Bloodstream Infections in Patients With Cancer
Authors: Sanchez J P , Contreras German , Tran Truc T , Simar Shelby , Hanson Blake , Marx Kayleigh , Zervos Marcus , Reyes Katherine , Munita Jose M , Shelburne Samuel A , Arias Cesar A , Aitken Samuel L , Aitken Samuel L
Published: January 2021

Background

E. faecalis (Efc) isolates are usually susceptible to ampicillin (AMP). AMP-based regimens are the standard of care for enterococcal infections, although other antibiotics are often used as definitive treatment. We thus compared outcomes of patients with cancer and Efc bacteremia treated with AMP-containing (ACR) and non-AMP-containing antibiotic regimens (NACR).

Methods

A multicenter, prospective, observational cohort study conducted at MD Anderson Cancer Center, Henry Ford Hospital, and Memorial Hermann Health System. Eligible patients were ≥ 18 years old, diagnosed with cancer, and had at least one Efc bloodstream isolate collected from 12/2015 to 12/2018. Patients with polymicrobial infections were excluded. Patients were divided into two groups: i) ACR and ii) NACR. ACR included patients who received AMP at any time during treatment; other antimicrobials were permitted. NACR patients did not receive AMP at any time. The primary outcome compared desirability of outcome ranking (DOOR) between ACR and NACR at day 14. The DOOR consisted of six hierarchical levels: 1 - death; 2 - inpatient without microbiological cure (MC) and with acute kidney injury (AKI); 3 - inpatient without MC and without AKI; 4 - inpatient admitted with MC and with AKI; 5 - inpatient with MC and without AKI; 6 - alive and discharged. Comparison of DOORs between ACR and NACR was performed using inverse probability of treatment weighted (IPTW) ordered logistic regression.

Results

Seventy-one patients were included (ACR, n = 35; NACR, n = 36). No difference was seen in DOORs at day 14 between ACR and NACR (odds ratio [OR] 1.14, 95% Confidence Interval [CI] 0.45 – 2.92, p=0.78). No difference was observed for all-cause mortality at day 14 (OR 0.6, 95% CI 0.09 – 3.77, p=0.58) or day 30 (OR 0.42, 95% CI 0.09 – 1.94, p=0.27). Patients treated with ACR received a lower median duration of other antibiotics at any point during treatment compared to NACR: daptomycin (2 v 4 days) vancomycin (2 v 4 days), and linezolid (1 v 2 days).

Conclusion

Patients with cancer and Efc bloodstream infections had similar outcomes when treated with ACR and NACR. ACR were associated with less use of broad-spectrum antimicrobials. Future research should focus on the ecologic impact of use of NACR.

Disclosures

Marcus Zervos, MD, Melinta Therapeutics (Grant/Research Support) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)
275. Comparison of Cefazolin versus Nafcillin for Methicillin-Susceptible Staphylococcus aureus Bacteremia with a Deep-Seated Source
Authors: Mersinger Katherine E , Athans Vasilios , Binkley Amanda , Binkley Shawn , Hamilton Keith W , Redline Gretchen , Saw Stephen , Dutcher Lauren
Published: January 2021

Background

Historically, anti-staphylococcal penicillins have been the treatment of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, cefazolin may have advantages over these agents including convenience and tolerability. Despite several studies finding similar rates of clinical efﬁcacy using cefazolin with fewer adverse drug events, some prescribers remain hesitant to use this agent due to concern for an inoculum effect in deep-seated infections. The purpose of this study was to compare cefazolin and nafcillin for the treatment of MSSA bacteremia with exclusively deep-seated sources.

Methods

Adult patients who were admitted with MSSA bloodstream infections (BSI) treated with cefazolin or nafcillin between March 2017 and October 2019 were identified. Patients were included if their BSI had a deep-seated source, defined as endocarditis, osteomyelitis, septic arthritis, pneumonia, prosthetic material, mediastinitis, or abscess. Patients were excluded if they had polymicrobial BSI, central nervous system infection, or received less than 7 days of therapy. The primary efﬁcacy outcome (PEO) was a composite of treatment failure, 60-day mortality, and 60-day infection relapse, and was assessed using multivariate logistic regression. The primary safety outcome (PSO) was discontinuation of therapy due to adverse drug events, which was assessed with a chi-square test.

Results

A total of 164 patients were included in this analysis (141 treated with cefazolin and 23 with nafcillin). There were no significant differences in the baseline characteristics collected (Table 1), and the most common deep-seated sources were prosthetic material and endocarditis. Treatment with nafcillin was not found to be protective against the PEO in multivariate analysis (aOR, 1.19; 95% CI, 0.42 to 3.39; P = 0.75), and the PSO was reached significantly more often among nafcillin recipients compared to those treated with cefazolin (7/23 [30.4%] versus 8/141 [5.7%], P < 0.0001).

Conclusion

Though the sample size was smaller than desired, cefazolin and nafcillin appeared to have similar efficacy for the treatment of MSSA BSIs with deep-seated sources. Nafcillin was associated with significantly more adverse drug events leading to discontinuation of therapy.

Disclosures

All Authors: No reported disclosures
278. Comparison of Oral Cephalexin Versus Oral Levofloxacin for Treatment of Uncomplicated Enterobacterales Bacteremia
Authors: Leung Thomas H , Tang Carolyn G , Ereshefsky Benjamin
Published: January 2021

Background

Aerobic gram-negative rods (GNR) are a common cause of bloodstream infections. While the use of oral antibiotics as step-down therapy for GNR bacteremia is generally accepted, there is debate as to which agents are best. Fluoroquinolones have high oral bioavailability but also have concerns for toxicity, while oral beta-lactams have lower achievable blood concentrations and require more frequent dosing. At Kaweah Delta Medical Center, patients are transitioned from IV antibiotics to oral levofloxacin or cephalexin. The purpose of this study is to determine if these two oral agents are comparable when used as step-down therapy for uncomplicated GNR bacteremia.

Methods

This was a single-center, retrospective study of adult patients who were admitted from May 2018 - May 2019 with a positive GNR blood culture. The primary objective was to assess treatment failure defined as a composite outcome of readmission due to recurrent bacteremia or mortality within 60-days. Secondary outcomes included subsequent Clostridioides difficile infection, emergence of resistant GNR bacteria, and hospital length of stay.

Results

A total of 82 patients met inclusion criteria. The combined median age of both treatment groups was 58.2 years (interquartile range [IQR], 46.7–73.5) and greater than 60% of patients were female. Most patients were Hispanic (45.1%) or non-Hispanic white (43.9%). The most common documented source of GNR bacteremia was the urinary tract (74.4%), and the most frequently recovered organism was Escherichia coli (78.0%). Patients were treated with IV antibiotics for a median treatment duration of 4 days (IQR, 4–5) and oral antibiotics for a median treatment duration of 10 days (IQR, 7.3–11) and 9 days (IQR, 7–11) for cephalexin and levofloxacin, respectively. The composite outcome occurred in 2 patients (4.3%) from the cephalexin group and 0 patients from the levofloxacin group (p=0.50). Positive cultures for resistant GNR were found for 3 patients in the cephalexin group. No patients developed subsequent C. difficile infections.

Conclusion

Patients who received cephalexin or levofloxacin did not have a significant difference in the composite primary outcome. These findings suggest that oral cephalexin is an effective step-down option to treat uncomplicated GNR bacteremia.

Disclosures

All Authors: No reported disclosures
280. Description of Transesophageal Echocardiography Prescribing Practices in non-Staphylococcus aureus Bacteremia with Application of Scoring Systems
Authors: Luttmann Kelly F , Headington Tre J , Hochanadel Alicia M , Deering Caytlin A , Harpenau Tara L
Published: January 2021

Background

In non-S. aureus gram-positive bacteremia (non-SAB), practices of obtaining transesophageal echocardiography (TEE) are mixed despite the availability of scoring systems in certain organisms (DENOVA for E. faecalis, HANDOC for non-beta hemolytic streptococci) that provide recommendations for TEE with scores 3 or higher. This study aimed to analyze the application of DENOVA and HANDOC scoring systems to coagulase-negative Staphylococci (CoNS), Enterococcus spp. and Streptococcus spp. in relation to TEE prescribing practices.

Methods

A retrospective, observational study was conducted at two tertiary care hospitals including patients with ≥1 positive blood culture for Enterococcus spp. or Streptococcus spp., or ≥2 positive blood cultures for CoNS with matching susceptibilities between November 2017 and November 2019. The primary outcome compared DENOVA and HANDOC scores in patients who received TEE vs. those who did not. Secondary outcomes included DENOVA and HANDOC scores in subgroup populations, adherence to DENOVA/HANDOC scoring systems, treatment characteristics, and patient outcomes.

Results

Of the 310 patients included, 96 (31%) underwent TEE and 214 (69%) did not. Fewer patients in the TEE group underwent transthoracic echocardiography: 29.2% vs. 69.9%, p< 0.01. Infectious Diseases providers were involved in all patients that underwent TEE. Median scores were significantly higher in all patients who underwent TEE; DENOVA: 2 (1–3) vs. 1 (1–2), p< 0.01; HANDOC: 3 (3–4) vs. 3 (2–3), p< 0.01. DENOVA and HANDOC scores were significantly higher in the TEE group in Enterococcus spp. and Streptococcus spp., respectively; overall adherence to scoring system recommendations in these groups was less than 60%. HANDOC score was higher in the TEE group for patients with CoNS and 87.5% of these patients with score ≥3 had endocarditis (versus 50% with DENOVA score). More patients in the TEE group had endocarditis 46.9% vs. 6.5%, p< 0.01.

Conclusion

DENOVA and HANDOC scores were significantly higher among TEE patients, but areas of improvement exist in relation to overutilization of TEE and development of scoring system for CoNS. Efforts to improve TEE utilization should be coordinated with Infectious Disease providers.

Disclosures

All Authors: No reported disclosures
282. Epidemiological Evaluation of Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Susceptible Staphylococcus aureus (MSSA) Bacteremia: A Comprehensive Cancer Center’s 10-Year Experience
Authors: Ford Charles R , Katzman Ju Hee , Greene John
Published: January 2021

Background

Coagulase-positive Staphylococcus aureus bacteremia among cancer patients carries significant morbidity and mortality. This study aims to compare the risk factors and clinical outcomes among cancer patients diagnosed with bloodstream infection (BSI) with methicillin-sensitive S. aureus (MSSA) or methicillin-resistant S. aureus (MRSA).

Methods

We performed a retrospective cohort study on all patients diagnosed with an active solid tumor or hematologic cancer with positive blood culture for S. aureus from January 2009 to May 2019. We collected data on demographics, comorbidities, malignancy type, venous access, neutropenia status, echocardiogram results, treatment (tx) duration, antibiotics usage pre/post culture, hospital LOS, infection severity, and 7-day and 30-day mortality. We used the Chi-square test to analyze categorical variables, t-test to analyze continuous variables, and the Kaplan-Meier survival curve and multivariate regression to analyze mortality.

Results

Two hundred eighty-three cases with malignancies and S. aureus BSIs were reviewed, and 168 were identified with BSIs for MRSA or MSSA during the ten years. The mean age for MRSA cases was 73.1 (±13.7) and 70.1 (± 14.6) for MSSA; male patients were most of the sex (P < 0.01). MRSA and MSSA bacteremia presented equally in hematologic malignancies, while MSSA was observed more in skin cancer than MRSA. Cancers that obstruct GU tracts may be associated with MRSA and MSSA from urine source as both were overrepresented in patients with bladder and rectal cancer. In most patients, the CVC was promptly removed and appropriate antibiotics were given promptly within 1 hour of the positive blood culture. For patients who underwent echocardiogram, most had a negative result in both groups. There was no significant difference for seven and 30-day mortality between the two groups. The mean hospital LOS was longer for MRSA cases (10.5 ± 13.5) versus MSSA cases (4.88 ± 9.1), (P < 0.01).

Figures 1 & 2. Kaplan-Meier Survival Curve Comparing 7 and 30-day Mortality of Cancer Patients with MRSA vs MSSA BSI

Figure 3 & 4. Distribution of Cancer Types for MRSA (n=84) and MSSA (n=84) BSI

Conclusion

Endocarditis with either MRSA or MSSA BSI is not a prominent finding among cancer patients at our institution. Given the extensive usage of CVCs and devices in patients with malignancies, prompt removal and antibiotic administration are essential to reduce morbidity; even then, the LOS for MRSA BSI remains longer than MSSA BSI.

Disclosures

All Authors: No reported disclosures
283. Epidemiology and Clinical Significance of Persistent Bacteremia in Severely Burned Patients
Authors: Townsend Lisa , Rizzo Julie , Markelz Ana E , Blyth Dana M
Published: January 2021

Background

Recent literature questions the utility of follow-up blood cultures (FUBC), especially for gram-negative bloodstream infections (BSIs). This has yet to be evaluated in the burn intensive care unit (BICU), where many BSIs are gram-negative. We evaluated the FUBC frequency, positivity rate, and clinical significance of persistent BSI (p-BSI) in BICU patients.

Methods

Patients ≥ 18 years old admitted to the US Army Institute of Surgical Research for combat-related thermal burns from 1/2003–6/2014 were included. P-BSI was defined as the same organism isolated from initial and FUBC (within 1–5 days). Non-p-BSI (np-BSI) included patients without subsequent isolation of the same organism between 1–5 days post-positive blood culture. Exclusion criteria were initial blood culture with usual skin flora, polymicrobial BSI, fungemia, and death within 24 hours of notification of initial positive blood culture. Those factors significantly associated with mortality on univariate analysis were evaluated with binomial logistic regression (BLR).

Results

Of 126 patients meeting inclusion criteria with BSI, 53 (42.1%) had p-BSI and 73 (57.9%) had np-BSI (table 1). 50 (67.6%) np-BSI patients had FUBC. P-BSI and np-BSI patients did not differ in age, gender, or race, but p-BSI and np-BSI patients had median total body surface area (TBSA) burns of 47 (IQR 34–63) and 35.3 (IQR 23.3–56.6), respectively (p=0.021). P-BSI patients had longer hospitalizations, ICU stays, and intubations (p< 0.01; table 1). Microbiology did not differ between p-BSI and np-BSI (p=0.517). Notably, 20 (37.7%) p-BSI patients died compared to 8 (10.8%) np-BSI patients (p< 0.001; table 2). BLR revealed that p-BSI (p=0.031), TBSA (p< 0.001), ISS (p=0.008), and length of ICU stay (p=0.002) and intubation (p< 0.001) were independently significantly associated with mortality.

Table 1: Clinical characteristics of burn patients with and without persistent bacteremia

Table 2: Univariate analysis evaluating associations with mortality in burn patients with bacteremia

Conclusion

P-BSI was common in this burn population. Severe burns and longer duration of hospitalization, ICU stays, and intubation, but not microbiology were associated with p-BSI. However, p-BSI (in addition to more traditionally identified risk factors like TBSA and duration of hospitalization, ICU, and ventilator days), was independently associated with increased mortality. FUBC may serve as an additional prognostic factor in burn patients with BSI.

Disclosures

All Authors: No reported disclosures
284. Evaluation of Oral Step-Down Therapy for Enterobacteriaceae Bloodstream Infection
Authors: Utley Sara , Bouknight Dawn , Patel Radha , Stock Kent
Published: January 2021

Background

Oral antibiotic stepdown therapy for Gram-negative (GN) bloodstream infection (BSI) appears to be a safe option, though high bioavailability drugs like fluoroquinolones (FQ) and trimethoprim-sulfamethoxazole are often recommended without clear evidence demonstrating superiority. Due to increasing concerns of FQ resistance and collateral damage with an increasing community C. difficile rate, our organization sought to reduce overall FQ use and a shift toward oral beta-lactams (BL) was observed. A review was conducted to assess the outcomes of this shift.

Methods

This retrospective cohort included all patients within our 3-hospital system who had a positive GN blood culture and were transitioned to oral therapy to complete treatment outpatient for bacteremia between Jan 2017-Sept 2019. The primary outcome was recurrent BSI within 30 days of completing initial treatment. Secondary outcomes included 30-day mortality, 30-day recurrence of organism at an alternate source, 30-day readmission, and 90-day BSI relapse.

Results

Of 191 GN BSIs, 77 patients were transitioned to oral therapy. The mean age was 68 years, 60% were female. The most common source of infection was described as urine (39/77), intra-abdominal (16/77), unknown (13/77). Mean total antibiotic duration (IV plus PO) was 14 days (range 7–33). Patients received an average of 5 days IV prior to transitioning to PO therapy. The most common PO class was a 1st gen cephalosporin (29/77), followed by BL/BL inhibitor (16/77), and a FQ (13/77). There were no 30-day relapse BSIs observed in this cohort. There was 1 patient discharged to inpatient hospice, and no other 30-day mortality observed. There were 4 recurrent UTIs observed within 30 days, none of which required readmission. Of the twelve 30-day readmissions, 1 was considered by the investigators to be related to the initial infection.

Conclusion

An opportunity for education regarding duration of therapy was identified. Oral beta lactam use in our limited population appears to be a reasonable option to facilitate discharge. Results should be confirmed in additional, larger studies.

Disclosures

All Authors: No reported disclosures
292. Impact of the BACT/ALERT VIRTUO blood culture system in the management of Staphylococcus aureus bacteremia
Authors: Chavez Miguel A , Munigala Satish , Burnham Carey-Ann , Warren David K
Published: January 2021

Background

Staphylococcus aureus bacteremia (SAB) is a major cause of mortality. Recovery of SA may be enhanced with new blood culture systems resulting in a longer observed duration of bacteremia.

Methods

We performed a 24-month retrospective study of adults hospitalized with SAB at a 1250-bed academic hospital. Between 1/2018-12/2018 the VersaTREK system was used and 1/2019-12/2019 the BACT/ALERT VIRTUO (VIRTUO) system was used. We excluded patients without an Infectious Diseases (ID) consult. We defined SAB duration as short (1–2 days), intermediate (3–6 days), or prolonged (>7 days). We compared SAB detection and management pre- and post-implementation of VIRTUO.

Results

456 patients had SAB during study period; 420 (92%) had ID consultation: 178 (42%) pre- and 242 (58%) post-implementation. Similar proportion of methicillin-resistant SAB was seen (44.9% pre- vs. 36.8% post-implementation, p=0.09). Post-implementation, patients were more likely to have intermediate (22.4% pre- vs. 40.1% post-implementation; p< 0.001) and prolonged SAB duration (3.9% pre- vs. 13.6% post-implementation; p< 0.001). Median time to positivity for the index blood culture was shorter (19.9 pre- vs. 15.0 hours post-implementation, p< 0.001). Dual anti-staphylococcal therapy was used more frequently in the post-implementation period (6.2% pre- vs. 15.7% post-implementation, p=0.003). No difference was noted in frequency of diagnostic studies (transesophageal echocardiography, magnetic resonance imaging, and computed tomography). Source control was similar (46.1% pre- vs. 45.0% post-implementation; p=0.84) but the median time to source-control was shorter post-implementation (4 pre- vs. 2 days post-implementation; p=0.02). Median planned duration of intravenous antibiotics did not vary between pre- and post-implementation periods (6 vs. 6 weeks, p=0.31). There was no difference in 90-day readmissions (38.2% pre- vs. 34.3% post-implementation; p=0.41).

Conclusion

VIRTUO blood culture system decreased time to positivity and increased frequency of prolonged SAB compared to the VersaTREK system. This resulted in increased use of dual anti-staphylococcal therapy and shorter time to source-control, but no difference in interventions, planned duration of antibiotics, or readmissions.

Disclosures

All Authors: No reported disclosures
299. Paediatric Collaborative Network on Infections in Canada (PICNIC) Study of the Current Landscape of Gram Negative Bacteremias
Authors: Lu Alice X , Tsang Kara , Barton Michelle , Frankel Craig , McDonald Jane , Bowes Jennifer , Gunawan John , Fanella Sergio , Alghounaim Mohammad , Coumeau Jeannette , Leifso Kirk , Slinger Robert , Robinson Joan , Khan Sarah
Published: January 2021

Background

Antimicrobial resistance is a public health threat, invasive infection from multi-drug resistant gram-negative (MDRGN) pathogens is associated with significant morbidity and mortality. The incidence of MDRGN bacteremia in Canada is rising, and pediatric data is limited.

Methods

This retrospective chart review of paediatric patients with gram negative bacteremia in a multicenter PICNIC database (n=7 centers) from 2013 to 2017. MDRGN was defined as enterobacteriaceae that were resistant to third generation cephalosporins (including ESBL, CPE). Ethics approval was obtained at all sites, and data was entered into a secure REDCAP database, descriptive statistics are described herein.

Results

Of the 676 bacteremia patients in the database, 214 (31.7%) were gram negative pathogens. E. coli was the most frequent pathogen (59.8%, of which 22 of 128 were MDR), followed by Klebsiella (31.8%, of which 9 of 68 were MDR). Of the 31 MDRGNs, 19 were ESBL, 1 was a CPE, and 11 were nonspecific mechanisms of resistance. There were no multidrug resistant Pseudomonas, Stenotrophomonas, or Acinetobacter. The majority of patient were less than 3 months of age (59.3%) and were male (58.8%). The majority had an underlying comorbid condition; hematoncologic diagnosis accounting for 14.5%. Length of stay varied from 1 to 742 days (mean 72, standard deviation 88). 11% required admission to ICU, 10% required removal of a intravascular catheter, 7% required a change in ventilation status, 2% requiring procedural source control, and there was an 8% mortality rate. Treatment duration greater than 14 days occurred in 123 patients (61% of patients).

Conclusion

This preliminary analysis of a multicenter review of pediatric gram negative bacteremias demonstrates a higher risk in neonates with comorbid conditions. A surprisingly prolonged treatment duration of greater than 14 days occurred in the majority of patients. Further analysis to assess factors associated with prolonged treatment durations, MDR infection, and complications is required. Gram negative bacteremia remains a significant cause of morbidity and mortality in pediatric patients.

Disclosures

All Authors: No reported disclosures
300. Pediatric Center Evaluation of the BioFire® Blood Culture Identification 2 Panel Versus the Original BioFire®FilmArray® Blood Culture Identification Panel for the Detection of Microorganisms and Resistance Markers in Positive Blood Cultures
Authors: Pierce Kristina B , Barr Rebecca , Hopper Aubrie , Bowerbank Charlotte , Shaw Anne , Pearson J , Aldave Matt , Tate Abby , Dickey Mandy , Holmberg Kristen , Lu Daisy , Koch Karen , Daly Judy
Published: January 2021

Background

Studies show a rising annual incidence of severe sepsis, with bloodstream infections continuing to impact children. Rapid identification of causative agents and timely administration of targeted therapy can positively impact patient outcomes and improve antibiotic stewardship.

The BioFire® Blood Culture Identification 2 (BCID2) Panel (BioFire Diagnostics, LLC), an updated version of the FDA-cleared BioFire® FilmArray® Blood Culture Identification (BCID) Panel, designed for use on positive blood cultures (PBCs), assesses 43 analytes, including 17 novel analytes (8 bacterial, 2 fungal, and 7 antimicrobial resistance genes), with a similar turnaround time.

Methods

De-identified residual PBCs for which clinician-ordered testing per standard of care (SoC) had been performed were enrolled and tested with an Investigation-Use-Only version of the BCID2 Panel. Only one positive bottle per patient was enrolled. Results of BCID2 and BCID were compared.

Results

116 PBCs (48 aerobic and 68 anaerobic) were evaluated using the BioFire BCID2 Panel and results were compared to the BioFire BCID Panel. Of the 116 cases, 103 were positive on both the BioFire BCID2 Panel and the BioFire BCID Panel. Ten cases were negative on both tests. While the two panels showed 97% agreement, three cases were discrepant. Using culture (SoC) as the tiebreaker, two cases were false positive and one case was false negative on the BioFire BCID Panel. In all three cases, results from culture and the BioFire BCID2 Panel were in agreement. As expected, no organisms were detected on the BioFire BCID2 Panel in PBCs from 10% (12/116) of PBC bottles where culture identified only organisms that are not part of the panel menu. With the BioFire BCID2 Panel’s expanded platform, two cases identified as Enterobacteriaceae on the BioFire BCID Panel were identified to the genus level on the BioFire BCID2 Panel; 31 cases detected to the genus level on the BioFire BCID Panel were identified to the species level on the BioFire BCID2 Panel.

Conclusion

Overall, the BioFire BCID2 Panel performed well against the BioFire BCID Panel for identification of bloodstream pathogens and provided additional discrimination of some pathogens to the genus or species level.

Data presented are from assays that have not been cleared or approved for diagnostic use.

Disclosures

All Authors: No reported disclosures
313. Using a Clinical Decision Prediction Tool to Improve Empirical Antimicrobial Therapy in Ceftriaxone-Resistant Enterobacterales Bloodstream Infections
Authors: McDougal Elizabeth , Justo Julie Ann , Kohn Joseph , Bookstaver P B , Winders Hana R , Al-hasan Majdi
Published: January 2021

Background

There are several clinical tools for prediction of antimicrobial resistance. However, their utility in management of bloodstream infections (BSI) due to resistant bacteria remains unclear. This quasi-experimental cohort examined the impact of utilization of the extended-spectrum beta-lactamase (ESBL) prediction score on time to initiation of appropriate antimicrobial therapy (AAT) in BSI due to ceftriaxone-resistant (CRO-R) Enterobacterales.

Methods

Adults with first episodes of monomicrobial BSI due to CRO-R Enterobacterales at Prisma Health-Midlands Hospitals in South Carolina from January 2010 to December 2017 were included. Antimicrobial stewardship intervention was implemented in January 2014 consisting of real-time alerts for positive blood cultures and rapid diagnostics for identification of bloodstream isolates. The ESBL prediction score was used to stratify risk of resistance prior to conventional antimicrobial susceptibility results. Student’s t-test was used to compare mean time to AAT before and after intervention.

Results

Among 92 patients with BSI due to CRO-R Enterobacterales, median age was 66 years, 52 (57%) were men, 68 (74%) had community-onset BSI, and 52 (57%) had urinary source of infection. Escherichia coli 52 (57%) and Klebsiella species 27 (29%) were the most common bloodstream isolates and the majority 63 (68%) produced ESBLs. There were no significant differences in demographics or clinical characteristics of patients before (n=45) and after (n=47) antimicrobial stewardship intervention. Mean time to AAT was 3.2 days prior and 1.7 days after utilization of ESBL prediction score (p=0.021). Results were consistent among ESBL-producing Enterobacterales (time to AAT 2.8 before and 1.8 days after intervention, p=0.025).

Conclusion

Utilization of the ESBL prediction score as part of a real-time antimicrobial stewardship intervention significantly reduced time to AAT in BSI due to CRO-R and ESBL-producing Enterobacterales. The ESBL prediction score represents a viable tool to improve antimicrobial management in clinical settings that lack access to multiplex PCRs for detection of antimicrobial resistance genes and novel methods for rapid phenotypic antimicrobial susceptibility testing.

Disclosures

Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)TRC Healthcare (Speaker’s Bureau)
49. Clinical Characteristics of the 2019 Eastern Equine Encephalitis Virus Outbreak in Michigan
Authors: Ladzinski Adam T , Rumschlag Matthew T , Mehta Aditya , Edewaard Eric , Boapimp Pimpawan , Morgan Larry , Hollstein Rolf Dieter , Jagger Brett W
Published: January 2021

Background

Eastern Equine Encephalitis Virus (EEEV) is a mosquito-borne alphavirus responsible for unpredictable outbreaks of severe neurologic disease in humans. While the vast majority of human EEEV infections are either asymptomatic or clinically nonspecific, a minority of patients develops neuroinvasive disease (EEE), which is a devastating illness with a mortality of at least 30%. No treatments are known to be effective. EEEV infection is relatively rare in the United States, with an annual average nationwide incidence of 7 cases between 2009 and 2018. However, 2019 was an exceptionally active year for human EEEV disease, yielding 38 nationwide confirmed cases, including 10 in Michigan, comprising the state’s largest outbreak to date.

Methods

EEE cases were identified by a regional network of physicians. Cases were defined by presentation with clinical symptoms of encephalitis, and by identification of EEEV IgM antibodies or RNA in cerebrospinal fluid (CSF), or EEEV-specific IgM in serum as confirmed by plaque reduction neutralization test. Radiographic images were evaluated and clinical data abstracted through chart review and clinical follow-up where possible.

Results

Records from 7 patients were identified and reviewed. The median age was 64, with a male predominance, and all presented in August. Notably, commercial arboviral CSF serology was uniformly negative on the initial CSF sample, and diagnosis was not made until a mean of 23 days (range: 12–38 days) after presentation. Testing in public health laboratories yielded the diagnosis in 5 out of 7 cases. Imaging findings were heterogeneous, but most patients exhibited abnormal findings in the thalamus and/or basal ganglia, and one patient displayed prominent pons and midbrain abnormalities. 4 patients died, while 2 patients survived with severe neurologic sequelae, and 1 patient recovered without sequelae. One patient underwent a limited postmortem examination, which revealed diffuse meningoencephalitis and focal vascular necrosis.

Conclusion

EEE is a frequently fatal condition whose diagnosis is often delayed, and for which no effective treatments are known. Improved diagnostics are needed to facilitate further clinical studies of EEE and encourage the development of potential therapies.

Disclosures

All Authors: No reported disclosures
51. A Review of Human Herpesvirus 6 and Central Nervous System Disease in Oncology Patients
Authors: Handley Guy H , Hasbun Rodrigo , Okhuysen Pablo C
Published: January 2021

Background

Human herpesvirus 6 (HHV-6) infects most of the human population. With immunosuppression it can reactivate and cause clinical syndromes of central nervous system (CNS) dysfunction. Much of the literature describes cases after hematopoietic stem cell transplantation (HSCT), ranging from encephalitis to a defined post-transplant acute limbic encephalitis syndrome (PALE). Outside of HSCT, studies of HHV-6 encephalitis in cancer patients are limited to case reports.

Methods

In this retrospective review, we present data from all patients admitted to MD Anderson Cancer Center between March 2016 and December 2018 that met established definitions for encephalitis, aseptic meningitis or HHV-6 PALE with detectable HHV-6 DNA in the cerebrospinal fluid (CSF) detected using either the Viracor or Biofire® Meningitis Encephalitis (ME) Panel testing platforms and no other identified etiology. We extracted demographic features, known risk factors, imaging findings, CSF analysis, treatments and patient outcomes from medical records.

Results

725 patients underwent HHV-6 testing during the study timeframe, with 19 (2.6%) cases of HHV-6 mediated CNS disease identified. Most patients, 13/19 (68%), had undergone HSCT. Median time to presentation was 31 days post-transplant. Survival at 240 days after transplant was 62% often with long-term neurologic sequelae. CSF tended to have lymphocyte predominance and nearly all patients had peripheral lymphopenia. Other at risk populations identified included 2/19 (11%) patients who received chimeric antigen receptor (CAR) T-cell therapy, 2/19 (11%) who received biologic immunotherapy, and 2/19 (11%) who had non-HSCT hematologic malignancy. Notable discordance among testing platforms was found in 5/9 (55%) of patients receiving both testing platforms.

CSF and Laboratory Analytes

Findings and Outcomes in HSCT Patients

Findings and Outcomes in Non-HSCT Patients

Conclusion

In addition to HSCT patients, HHV-6 reactivation leading to CNS disease also occurs in settings such as following adoptive T cell therapy or biologic immunotherapy. Significant diagnostic discordance exists between testing platforms.

Disclosures

Rodrigo Hasbun, MD, MPH, Biofire (Consultant)
52. A Nationwide Analysis of the Trends and Outcomes of Cryptococcal Meningitis in the United States
Authors: Mansoor Armaghan-e-Rehman , Sarwari Arif R
Published: January 2021

Background

Cryptococcal Meningitis (CM) is the most common presentation of invasive cryptococcosis. Seen in patients with and without HIV, CM is associated with significant morbidity and mortality. We present findings from a nationwide analysis of patients admitted with CM in the United States between 2007 and 2016.

Methods

The national inpatient sample (NIS) database was queried for all inpatient visits for Cryptococcal Meningitis between January 2007 and December 2016. Logistic regression models were used to determine risk factors for mortality, prolonged admissions, and delays in obtaining an initial lumbar puncture.

Results

The number of admissions for CM decreased during the study interval, from 3590 in 2007 to 2830 in 2016. Mortality did not change over this period (9.9%), however length of stay and inpatient cost significantly increased (P = 0.003 and P < 0.001 respectively). The proportion of patients with HIV declined from 70.7% to 54.0% (P < 0.001). HIV patients had a lower risk of mortality (OR = 0.77, CI 0.68–0.86, P < 0.001), whereas Africa-American, Hispanic and Native American ethnicities had a significantly increased association with mortality. Delay in lumbar puncture beyond the first 24 hours was independently associated with mortality, with an OR of 1.55 (CI 1.31–1.82, P < 0.001). . Patients admitted on a weekend, those of African-American ethnicity, and those without a known history of HIV were more likely to have delays in obtaining an early LP.

Conclusion

Inpatient mortality for patients with CM continues to remain high, with an increasing proportion of patients without underlying HIV infection. We found significant deviations in management of CM from IDSA guidelines, and an independent association of delay in early lumbar puncture with worsened patient outcomes.

Disclosures

All Authors: No reported disclosures
53. Incidence of Bloodstream Infections and Outcomes in Patients with Severe COVID-19 Pneumonia
Authors: Papamanoli Aikaterini , Yoo Jeanwoo , Mojahedi Azad , Jacob Robin , Grewal Prabhjot , Dhaliwal Simrat , Coritsidis Alexandra , Nakamura Jacquelyn , Fung Jenny , Hotelling Jessica , Rawal Sahil , Karkala Nikitha , Tsui Stella T , Abata Joshua , Psevdos George , Kalogeropoulos Andreas , Marcos Luis
Published: January 2021

Background

Coronavirus disease 19 (COVID-19) leading to acute respiratory distress syndrome is associated with need for intensive care (IC), mechanical ventilation (MV), and prolonged recovery. These patients are thus predisposed to blood stream infections which can worsen outcomes. This risk may be aggravated by adjunctive therapies.

Methods

We reviewed the medical records of all adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (requiring high-ﬂow O2). Patients who received MV or died within 24h were excluded. Patients were followed until death or hospital discharge. We reviewed positive blood cultures (PBC) for pathogenic microorganisms, and calculated the incidence of bacteremia, rates of infective endocarditis (IE), and impact on mortality. Microbes isolated only once and belonging to groups defined as commensal skin microbiota were labelled as contaminants. We also examined the impact of adjunctive therapies with immunosuppressive potential (steroids and tocilizumab), on bacteremia.

Results

A total of 469 patients with severe COVID-19 pneumonia were included (Table 1). Of these, 199 (42.4%) required IC and 172 (36.7%) MV. Median length of stay was 13 days (8–22) and 94 (20.0%) had PBC. Of these, 43 were considered true pathogens (bacteremia), with predominance of E. faecalis and S. epidermidis, and 51 were considered contaminants (Table 2). The incidence of bacteremia (43/469, 9.2%) was 5.1 per 1000 patient-days (95%CI 3.8–6.4). An echocardiogram was performed in 21 patients, 1 had an aortic valve vegetation (IE) by methicillin sensitive S. aureus. Bacteremia rates were nonsignificantly higher with steroids (5.9 vs 3.7 per 1000 patient-days; P=0.057). Use of tocilizumab was not associated with bacteremia (5.8 vs 4.8 per 1000 patient-days; P=0.28). Mortality was nonsignificantly higher in patients with (15/43, 34.9%) vs. without (108/426, 25.4%) bacteremia (P=0.20). Length of stay was the strongest predictor of bacteremia, with risk increasing by 7% (95%CI 6%-9%, P< 0.001) per additional day.

Cohort Characteristics of Patients with Severe COVID-19 Pneumonia on High-Flow O2 (N= 469)

All Microorganisms Isolated from Blood Cultures

Conclusion

The incidence of bacteremia was relatively low and IE was uncommon in this study of severe COVID-19 patients. Risk of bacteremia increased with longer hospital stay and with steroids use, but not with tocilizumab.

Disclosures

All Authors: No reported disclosures
57. clinical Characteristics and Outcomes of Patients Hospitalized with COVID-19 in New Orleans, LA: A Cohort Study
Authors: Silver Victoria , Chapple Andrew , Feibus Allison H , Beckford Jeremy , Halapin Natalie , Barua Delphi , Gordon Angellica , Baumgartner William , Vignes Seth , Clark Cullen , Kamboj Sanjay , Lim Stephen , Mackey Scott , Seal Paula , Kanter Joseph , Clement Meredith E
Published: January 2021

Background

In Louisiana, deaths related to COVID-19 have disproportionately occurred in Black persons. Granular data are needed to better understand inequities and develop prevention strategies to mitigate further impact on Black communities.

Methods

We conducted a retrospective cohort study of patients admitted to an urban safety net hospital in New Orleans, LA with reactive SARS-CoV-2 testing from March 9–31, 2020. Clinical characteristics and outcomes of Black and other racial/ethnic group patients were compared using Wilcoxon rank-sum test and Fisher’s exact tests. We examined Day-14 status using an ordinal scale to assess race and outcome.

Table 1. Demographics and Comorbidities by Race for Patients Hospitalized with COVID-19

Table 2. Clinical Characteristics at Presentation by Race for Patients Hospitalized with COVID-19, March 2020

Results

This study included 249 patients. Median age was 59, 44% were male, 86% were age ≥65 years or had ≥1 comorbidity. Overall, 87% were Black, relative to 55% Black patients typically hospitalized at our center. Black patients had longer symptom duration at presentation (6.41 versus 5.88 days, p=0.05), and were more likely to have asthma (p=0.008), but less likely to have dementia (p=0.002). There were no racial differences in initial respiratory status or laboratory values other than higher initial LDH in Black patients. Patient age and initial oxygen requirement, but not race (adjusted proportional odds ratio = 0.92, 95%CI: 0.70–1.20), were associated with worse Day-14 outcomes.

Figure 1: Admissions over time by Race

Figure 2a: Hospital outcomes by Race over the Follow-up period

Figure 2b: Day-14 Outcomes by Race

Conclusion

Our results demonstrate minor racial differences in comorbidities or disease severity at presentation, and Day-14 outcomes were not different between groups. However, Black patients were disproportionately represented in hospitalizations, suggesting that prevention efforts should include strategies to limit SARS-CoV-2 exposures in Black communities as one step towards reducing racial inequities related to COVID-19.

Figure 3a: Logistic Regression for Initial Oxygen Requirement

Figure 3b: Cumulative Logistic Regression for Ordinal Day-14 Outcomes

Disclosures

Meredith E. Clement, MD, FHI360 (Consultant)Gilead (Research Grant or Support)Janssen (Scientific Research Study Investigator)
58. Clinical Characteristics of SARS-CoV-2 Among Confirmed and Suspected Cases in Tennessee
Authors: Talj Rana , Rankin Danielle A , Nicotera Janet , Howard Leigh , Halasa Natasha B
Published: January 2021

Background

On March 11, 2020, a pandemic due to SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), was declared. The disease spectrum varies from asymptomatic detection to severe disease. Data on community versus hospitalized cases are limited. We aim to evaluate and compare the epidemiological and clinical characteristics associated with SARS-CoV-2 infection among suspected and confirmed COVID-19 cases primarily diagnosed in the ambulatory setting and compare their illness presentation.

Methods

We are prospectively enrolling a longitudinal cohort of laboratory-confirmed or suspected COVID-19 subjects and their close contacts. Suspect cases are defined as anyone who developed fever and/or Covid-19 like-symptoms in the post-Covid-19 era without proven SARS-CoV-2 detection. We consented and interviewed subjects over the phone to capture detailed sociodemographic data, medical and social histories, and clinical characteristics of the illness.

Results

From March 20 to June 16, 2020, 463 subjects were enrolled (Figure 1). Of those, 178 were SARS-CoV-2 positive [164 adults and 13 pediatric (< 18 years) cases] and 192 were COVID-19 suspected (111 adults and 78 pediatric cases). Adult confirmed cases were more likely to be Hispanic and have an underlying medical condition but less likely to be white compared to suspected cases (Table 1). Pediatric confirmed cases were more likely to be Hispanic and have smoke exposure, but less likely to have a travel history compared to suspected cases (Table 1). Both adult and pediatric confirmed subjects had fatigue, headache and cough as the most common symptoms reported. Cough, muscle aches and chest tightness were more likely to be reported in pediatric confirmed than suspected cases; whereas loss of taste, smell and appetite, diarrhea and fever ≥ 100.4 were documented more often in adult confirmed than suspected cases (Figure 2).

Figure 1. Cumulative enrollment of subjects by day

Table 1. Sociodemographic characteristics among confirmed and suspected COVID-19 cases

Figure 2. Adults and pediatrics, confirmed and suspected cases, by clinical presentation

Conclusion

We observed differences of clinical presentation between confirmed and suspected cases among both pediatric and adult participants. Further research is needed to determine whether these differences are due to disease severity or absence of proven COVID-19. We are collecting serial nasal swabs, blood and stool specimens, on which future testing will confirm SARS-CoV-2 infection in suspected subjects.

Disclosures

Danielle A. Rankin, MPH, CIC, Sanofi Pasteur (Grant/Research Support, Research Grant or Support) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)
59. Persistence of Respiratory and Non-respiratory Symptoms Among COVID-19 Patients Seeking Care at an Ambulatory COVID-19 Center
Authors: Ramakrishnan Aditi , Zreloff Jennifer , Moore Miranda , Bergquist Sharon H , Cellai Michele , Higdon Jason , O’Keefe James B , Roberts David L , Wu Henry M
Published: January 2021

Background

While hospitalized COVID-19 patients are well described in the literature, studies of the natural history and ambulatory cases are limited. We aim to describe the symptoms and clinical course of COVID-19 among ambulatory patients seen at the Emory University multidisciplinary Acute Respiratory Clinic (ARC) developed to care for patients with confirmed or suspected COVID-19.

Methods

PCR-confirmed COVID-19 cases seen at ARC from 4/3–5/16/2020 were included in a retrospective chart review. Encounters were classified as acute, subacute, or convalescent depending on the duration since illness onset (< 1, 1–4, or >4 weeks, respectively). Demographic, clinical, physical exam, diagnostic test, and disposition data were abstracted and analyzed with standard descriptive statistics.

Results

Among 404 visits at ARC, 127 (31.4%) were for confirmed COVID-19 illness (107 unique patients with 1–4 visits). The majority (75.7%) of patients were female, and the median age was 55 years (range 24–89). Patients presented during acute, subacute, and convalescent phases of illness (15.7%, 58.3%, and 26.0%, respectively; Table). Prevalent co-morbidities included hypertension (39.3%), obesity (27.1%), diabetes (20.6%), and asthma (21.5%). While measured or subjective fever was reported in the majority of acute visits (60.0%), it was less common in subacute and convalescent encounters (27.0% and 30.3%). Cough was commonly reported in acute, subacute, and convalescent visits (70.0%, 79.7%, 66.7%), as were dyspnea on exertion (45.0%, 70.3%, 66.7%) and chest tightness (40.0%, 40.5%, 60.6%). Although smell or taste alteration was present in almost half of acute and subacute patients, it was only reported in a quarter of convalescent patients. Among the three stages of illness, transfers from ARC to the ED or direct hospitalizations occurred in 15.0%, 23.0%, and 12.1% of acute, subacute and convalescent visits, respectively.

Table Timecourse of Symptoms among COVID-19 Patients in the Ambulatory Context

Conclusion

Following acute illness, COVID-19 patients can experience persistent symptoms, primarily respiratory symptoms, which can be severe enough to warrant hospitalization. Clinics evaluating recovering patients should prepare to manage these symptoms. Further study of the pathophysiology and treatment of persistent pulmonary symptoms in COVID-19 is needed.

Disclosures

All Authors: No reported disclosures