bluuebunny/crossref_metadata_2025_split huggingface dataset:
301. Penicillin Versus Cefazolin or Anti-staphylococcal Penicillins for Penicillin-Susceptible Staphylococcus aureus Bacteremia
Authors: Aldhaeefi Mohammed , Pearson Jeffrey , Kanjilal Sanjat , Dionne Brandon 
Published: January 2021

Abstract

Background
Staphylococcus aureus bacteremia is a significant cause of mortality. Penicillin (PCN) may have a role in the treatment of penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia as it has a narrower spectrum of activity than cefazolin and is better tolerated than antistaphylococcal penicillins (ASPs). The aim of this study is to evaluate the safety and effectiveness of PCN versus cefazolin or ASPs in the treatment of PSSA bacteremia.

Methods
This is a single-center, retrospective study at a tertiary academic medical center. All patients with a PSSA blood culture from January 1, 2012 to September 1, 2019 were screened. Patients were excluded if they were treated with a definitive antibiotic (defined as antimicrobial therapy received 72 hours after positive blood culture) other than the study comparators, or if they received combination antibiotic therapy &gt;72 hours from the initial positive blood culture result. The primary outcome was 60-day clinical failure, which was a composite endpoint of change in antibiotic after 72 hours of definitive therapy, recurrence of PSSA bacteremia, infection-related readmission, or all-cause mortality.

Results
Of 277 patients with PSSA bacteremia, 101 patients were included in the study; 62 (61%) were male and 11 (11%) had a β-lactam allergy. At baseline, 40 patients (40%) had hardware, 25 (25%) had an intravenous line, 6 (6%) were on dialysis, and 4 (4%) had active IV drug use, with similar distribution across antibiotic groups. Penicillin was the most common antibiotic used (Table 1). There was a significant difference among groups with respect to the 60-day clinical failure (log-rank p=0.019). In terms of unadjusted 60-day clinical failure, penicillin had similar outcomes to cefazolin (95% CI -0.29 to 0.104, p=0.376), however, it had statistically significant better outcomes in comparison to the ASPs, nafcillin or oxacillin (95% CI 0.023 to 0.482, p=0.031) (Table 1).
Table 1. 60-day outcomes of PSSA bacteremia

Conclusion
Penicillin is effective and safe in the treatment of PSSA bacteremia and may be preferable to antistaphylococcal penicillins

Disclosures
All Authors: No reported disclosures
302. Peripheral IV catheters, a common source of healthcare-associated Staphylococcus aureus bacteremia
Authors: Young Heather , Aragon Deborah , Knepper Bryan C , Hussain Cory , Jenkins Timothy C 
Published: January 2021

Abstract

Background
Healthcare-associated S. aureus bacteremia (HA-SAB) has traditionally been attributed to surgical site infections (SSI) or central line-associated bloodstream infections. However, peripheral IV catheters (pIV) are increasingly recognized as cause of HA-SAB. This study evaluates risk factors for HA-SAB due to pIV.

Methods
This is a retrospective, case-control study of adult patients hospitalized at Denver Health Medical Center with HA-SAB (SAB presenting with hospital-onset [≥3 days after hospitalization] or community-onset attributed to recent hospitalization [discharge ≤7 days prior]). The time period ranged from Jan 1, 2016 to Nov 30, 2019. Cases were reviewed by an infectious diseases physician to determine the source of SAB. PIV-related SAB was defined as phlebitis, cellulitis, and/or drainage at the site of a previous pIV AND no other source or another less likely source based on progress notes and microbiology results. Three controls were matched to each pIV-related SAB case based on the age of the patient (±5 years) and the date the pIV was placed (±3 days). Patients who were admitted for elective procedures, to psychiatry, to obstetrics, and those who died within 2 days of pIV placement were excluded.

Results
There were 376 episodes of SAB during the study period; 313 were community-onset while 63 were HA-SAB (50 hospital-onset and 13 community-onset attributed to hospitalization). PIV was the most common cause of HA-SAB (n=20, 29.4%); other common causes were SSI (n=10, 15.9%), source present at admission (n=8, 12.7%), and pneumonia (n=7, 11.1%). The median age of patients with pIV-related SAB was 53 years (SD 15.6), and 85% were male. The median duration of pIV was 5 days (SD 2.8). Twenty percent was MRSA.
As compared to controls, pIV in immunocompromised individuals and those placed by emergency medical services (EMS) were more likely to develop SAB (OR 11.8, 95% CI 2.5–56.5 and OR 6.9, 95% CI 6.9–24.0, respectively). Age, gender, pIV location, and duration of pIV were not associated with development of SAB.

Conclusion
PIV placed by EMS are more likely to cause SAB than those placed in the hospital. Facilities should consider changing these pIV promptly upon admission to the hospital and work with EMS to improve pIV placement technique.

Disclosures
All Authors: No reported disclosures
303. Physiological Changes Due to Bloodstream Infection in Intensive Care Unit Patients Differ According to Transplant Status
Authors: Zimmet Alex , Lake Douglas , Zimmet Amanda M , Gadrey Shrirang M , Bell Taison , Moorman Randall , Moore Christopher 
Published: January 2021

Abstract

Background
Transplant recipients are at increased risk of bloodstream infection (BSI), which often leads to critical illness. Due to immunosuppression, BSI in these patients may manifest with different pathophysiology compared to non-transplant recipients. We aimed to identify different trends in the pathophysiology of critically ill patients with BSI based on transplant status.

Methods
We reviewed data from patients admitted to the medical and surgical/trauma intensive care units (ICUs) at the University of Virginia Medical Center from 2011 to 2015. We included both solid organ and hematopoietic stem cell transplant recipients. We performed univariate logistic regression modeling to evaluate trends in different physiological features in both transplant and non-transplant recipients in the 96 hours surrounding a positive blood culture. We then performed multivariate logistic regression modeling to identify features independently associated with a positive blood culture in the next 24 hours in transplant recipients.

Results
We analyzed 9,954 ICU patient-admissions (including 505 transplant recipients), with a total of 144 patient-years of physiological data, 1.3 million hourly measurements, and 15,577 blood culture instances. Of the 1,068 blood culture instances in transplant recipients, 125 (12%) were positive, compared to 1,051 of 14,509 (7%) blood culture instances in non-transplant recipients. Critically ill transplant recipients with BSI had greater abnormalities in vital signs, oxygen requirement, markers of organ damage, APACHE score, and Charlson Comorbidity Index (CCI) compared to non-transplant recipients (Figure 1). Trends in many of these features also differed based on transplant status. The multivariable logistic regression model of BSI in transplant recipients included, in decreasing strength of association: total bilirubin, systolic blood pressure, fraction of inspired oxygen, number of intravenous lines, and CCI. This model had an AUC of 0.75.
Figure 1. Trends in pathophysiological abnormalities in 9,954 critically ill patients with BSI based on transplant status, 2011–2015. Each graph demonstrates the average value of the physiological variable over time relative to the acquisition of a positive blood culture. Blue curves depict trends in transplant recipients, while red curves depict trends in non-transplant recipients. We assessed 108 physiological features and show the 24 features with the greatest change around the time of blood culture.

Conclusion
Critically ill transplant recipients have a higher prevalence of BSI and different pathophysiological manifestations of BSI compared to non-transplant recipients. This may have implications regarding early detection and treatment of BSI in these patients.

Disclosures
Randall Moorman, MD, Advanced Medical Predictive Devices, Diagnostics, and Displays (Board Member, Shareholder)
305. Prevalence of Ceftriaxone Susceptible, Piperacillin-tazobactam Non-susceptible Escherichia coli Bacteremia in Patients with Hematologic Malignancy
Authors: Spitznogle Sarah L , Rausch Caitlin R , Bhatti Micah M , Shelburne Samuel A , Aitken Samuel L 
Published: January 2021

Abstract

Background
Piperacillin-tazobactam (TZP) is common empiric and targeted therapy for gram-negative bacteremia in patients with hematologic malignancy. Resistance to TZP tends to occur concurrently with ceftriaxone (CRO) resistance; however, the prevalence of TZP nonsusceptibility in CRO susceptible Escherichia coli (E. coli) in patients with hematologic malignancy is unknown. Therefore, we sought to determine the prevalence of TZP nonsusceptible, CRO susceptible E. coli bacteremia at a cancer center.

Methods
This is a retrospective cohort study of adult (age &gt; 18) patients with E. coli bacteremia admitted to the Leukemia or Stem Cell Transplant (SCT) services at The University of Texas MD Anderson Cancer Center (MDACC) between 8/2016 and 7/2019. Isolates were categorized according to current CLSI resistance breakpoints. A first isolate was defined as the first positive blood culture and subsequent episodes of bacteremia were defined as any E. coli isolate obtained at least 24 hours after the first negative blood culture.

Results
The overall prevalence of TZP resistant CRO susceptible E. coli from 404 isolates was 7.7% and varied by service. There was a higher prevalence in the Leukemia service compared to SCT, 9.8% vs 2.5%, respectively (p &lt; 0.01). 46% of isolates were CRO nonsusceptible, of which 91% were extended-spectrum beta-lactamase (ESBL) producers, identified by Vitek 2 or Accelerate Pheno. The TZP MIC50 was 4ug/ml, MIC90 was 128ug/ml, with an MIC range of 3ug/ml to ≥ 256ug/ml. The TZP MIC distribution varied based upon CRO phenotype. In CRO susceptible isolates the MIC50 and MIC90 were 4ug/ml and 64ug/ml, respectively, compared to 8ug/ml and 128ug/ml in CRO nonsusceptible isolates (p &lt; 0.01). TZP resistance was more common in CRO nonsusceptible isolates (31.6% vs 12.0%, p &lt; 0.01) and was more frequent with subsequent episodes of bacteremia compared to the first (39.5% vs 20.1%, p &lt; 0.01).

Conclusion
In patients with hematologic malignancy and E. coli bacteremia, TZP resistance is common with significant variations by CRO phenotype. TZP resistance becomes more common with subsequent episodes of bacteremia compared to the first. The clinical implications and genetic cause of this phenotype is currently unknown and warrants further investigation.

Disclosures
All Authors: No reported disclosures
306. Rapid Detection Of Bloodstream Infections, Including Molecular Characterization, From Whole Blood
Authors: Kadoom Aram , Lockhart Daniel , Kadoom Yassar , Fauci Sonia La , Rodgers Andrew , Turner James , Bennett Helen , Jay Paul , Thaker Sumi , Mullen William 
Published: January 2021

Abstract

Background
Diagnosis of bloodstream infections (BSI) and treatment with appropriate antimicrobials is dependent upon fast and accurate information about the microorganism(s). The long time taken for a blood culture result, microbial identification and antimicrobial susceptibility testing (AST), can lead to poor antimicrobial stewardship. Many antimicrobial change decisions are based on the results of a Gram stain, with this being the first result available. Having results from a rapid test, direct from blood, which can confirm BSI and characterize the causative pathogen(s) would provide an improvement in antimicrobial stewardship and patient care.

Methods
SepsiSTAT® is a rapid molecular test, developed by Momentum Bioscience Ltd, for the detection of BSI, with a time-to-result of &lt; 4 hours. It uses whole blood to detect viable microorganisms whilst also providing molecular characterization. Microorganisms are extracted from the sample using a proprietary process involving capture on magnetic microbeads. This is followed by Enzymatic Template Generation and Amplification (ETGA®) for ultra-sensitive, universal detection of viable bacterial and fungal species, based on detecting microbial DNA polymerase activity. Simultaneously, molecular characterization also provides genus/species identification. The detection limits of SepsiSTAT® were evaluated for a broad panel of microorganisms, representing 80% of BSI reported to Public Health England (2018 report).

Results
These results show a median detection limit (n=5) of &lt; 10 cfu/mL in blood for microorganisms representing 77.4% of reported BSI, including key organisms such as E. coli, S. epidermidis and C. albicans. Notably, S. aureus, P. aeruginosa, E. faecalis, P. mirabilis and S. marcescens were all detected at &lt; 1 cfu/mL.

Conclusion
SepsiSTAT® can detect microbes in low numbers, with a turnaround time substantially faster than traditional blood culture. Future development will aim to shorten time-to-results to &lt; 3 hours, further benefiting patient outcomes and antimicrobial stewardship. Future studies in a clinical setting will seek to further demonstrate the efficacy and rapid turnaround time of the SepsiSTAT® test.

Disclosures
All Authors: No reported disclosures
307. Rapid Resistance Development to Three Antistaphylococcal Therapies in Daptomycin-tolerant Staphylococcus aureus Bacteremia
Authors: Miller Christopher R , Monk Jonathan , Berti Andrew David 
Published: January 2021

Abstract

Background
We report a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which over 30 days developed resistance to all three primary antistaphylococcal antibiotics. Index blood cultures displayed susceptibility to vancomycin (VAN, MIC=1), ceftaroline (CPT, MIC=0.5) and daptomycin (DAP, MIC=0.5). The patient was maintained on VAN/CPT with negative blood cultures by hospital day 7. The regimen was later modified to DAP/piperacillin-tazobactam. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to VAN (MIC=2) and CPT (MIC=2), and resistance to DAP (MIC=4).

Methods
Isolates were collected from the initial bacteremia episode (B325) and the recurrence (B326). In-vitro one-compartment pharmacokinetic/pharmacodynamic modeling was performed on each isolate to determine which antibiotics or combinations would effectively eradicate cultures. Regimens examined included DAP (10mg/kg), DAP/cefazolin (CFZ), VAN/CFZ and penicillin/clavulanate. Draft whole-genome sequences are pending for each clinical isolate using hybrid assembly (Unicycler v0.4.2) of MinION and Illumina (150bp PE) reads.

Results
DAP/CFZ combination reduced viability of both B325 and B326 below limit of detection by 12 hours and maintained efficacy for 72 h. DAP, initially effective in reducing B326 cell concentrations below limit of detection, allowed regrowth by 36 h. All other modeled therapies were less effective. Interestingly, DAP took significantly longer to kill B325 relative to S. aureus collected contemporaneously from other patients. For DAP-containing regimens, the time to 3-log viability reduction (MDK99.9) was five-fold longer in B325 compared to similar clinical isolates with the same DAP MIC. Comparative genomics of sequential isolates is pending, although single nucleotide polymorphisms in vraT and mprF were identified in B326 compared to B325.

Conclusion
Delayed kill kinetics of B325 when exposed to DAP may indicate antibiotic tolerance, which could partially account for B325’s rapid transition to a multi-drug resistant organism. DAP/CFZ therapy appears to be the most active combination against both antibiotic-tolerant and multidrug resistant S. aureus strains.

Disclosures
All Authors: No reported disclosures
308. Re-purposing Beta-lactam Antibiotics as Fluoroquinolone Sparing Stepdown Therapy for the Treatment of Enterobacteriales Bloodstream Infections
Authors: Davis Matthew , McManus Dayna , Ruggero Michael , Topal Jeffrey E 
Published: January 2021

Abstract

Background
Oral antimicrobial therapy for Enterobacteriales bloodstream infection (EB-BSI) is advantageous to reduce the risk of central line complications, cost of care, and length of stay. Fluoroquinolones (FQ) given their high bioavailability have been utilized as the standard for stepdown therapy (SDT) for EB-BSI. Given the recent increased warnings around FQ use including Clostridioides difficile infection (CDI) and the increasing FQ resistance alternative oral options for treatment are warranted. Recent literature has suggested beta-lactams (BLM) may be an option for EB-BSI. To enhance the antimicrobial stewardship goal of reducing FQ use, our team began recommending de-escalation to a BLM for EB-BSI and the objective of this study is to evaluate the outcomes of this approach.

Methods
This study was a retrospective chart review of patients with EB-BSI due to ceftriaxone sensitive monomicrobial E. coli, Klebsiella spp., or P. mirabilis who received a BLM or a FQ as SDT. Patients were excluded if &lt; 18 years of age; pregnant; ANC &lt; 1000 cells/µL; had endocarditis, a bone/joint, or a CNS infection; discharged to hospice or expired prior to discharge; anaphylactic BLM allergy; or prior kidney transplant. SDT was defined as a switch to a definitive oral antibiotic after empiric IV therapy. The primary outcome was clinical cure defined as completion of therapy without signs of infection (increase in WBC &gt; 2000 cells/mL if WBC was ≥ 12,000 cells/mL, fever (&gt;38°C), or change in antibiotic due to failure). Secondary outcomes included 30 day re-admission rates, reinfection rate defined as positive culture within 30 days of completion of therapy, antibiotic associated adverse events defined as side effects leading to discontinuation and/or CDI within 90 days from start of treatment.

Results
A total of 159 patients were included in the study (Figure 1). The BLM patients had a higher median age (78 vs 72, p=0.008), higher median PITT bacteremia score (2 vs 1, p=0.037), were less likely to be immunosuppressed (9% vs 25%, p=0.045), and had shorter median duration of therapy (13 vs 14, p=0.034). There was no difference in the primary or secondary outcomes (Table 2).

Conclusion
BLM may enhance stewardship efforts as a FQ sparing option for treatment of EB-BSI; however, prospective studies in this area are warranted.

Disclosures
All Authors: No reported disclosures
309. The Impact of Addiction Medicine Consultation on Discharges Against Medical Advice in Patients with Opioid Use Disorder and Staphylococcus Aureus Bacteremia
Authors: Spivack Stephanie , Mueller Daniel , Axelrod Peter , D’Orazio Joseph 
Published: January 2021

Abstract

Background
People who inject drugs (PWID) are at risk for infectious complications of their injection practices, including Staphylococcus aureus (SA) bacteremia. Prolonged hospitalization is sometimes required; however, rates of discharges against medical advice (AMA) are elevated in this patient population. Inadequate control of pain and opioid withdrawal are commonly cited. Our aim was to assess the effectiveness of addiction medicine consultation for preventing AMA discharges.

Methods
We performed a retrospective chart review of adult PWID admitted to an urban hospital with SA bacteremia between August 2016 and May 2018. Demographics, HIV and HCV status, and presence or absence of addiction medicine consultation were recorded. We assessed whether discharges were planned or AMA; the number of hospitalizations at 30 days, 90 days, and 1 year from index admission; and death within one year. EpiInfo6 was used for data analysis.

Results
A total of 360 patients with SA bacteremia were reviewed. Of these, 101 reported intravenous opioid use at admission. Average age was 37 years, and 64% were male. HIV and HCV were present in 13% and 82% of patients, respectively. Addiction medicine was consulted on 29 patients. Of these, 4/29 (13.8%) left AMA, compared to 27/72 (37.5%) of patients without an addiction consult (RR = 0.3678 [95% CI = 0.1412 - 0.9583], p = 0.02).
Patients receiving addiction medicine consultation averaged 0.17 readmissions within 30 days of their index admission, compared to 0.39 readmissions in the group without addiction medicine consult (p = 0.27). Readmissions at 90 days and 1 year were also lower but not statistically significant. At 1 year, 6 deaths were observed; 2 who had addiction medicine consultation and 4 who did not.

Conclusion
Consultation with an addiction medicine specialist significantly reduced the number of patients discharged AMA in a high-risk cohort of PWID presenting with SA bacteremia. Numerically fewer readmissions occurred after consultation, though this difference was not statistically significant. Mortality in both groups was low. There were high rates of HIV and HCV in this patient population, suggesting a particularly vulnerable patient population, which warrants further study.

Disclosures
All Authors: No reported disclosures
311. The Role of Transthoracic Echocardiography in Staphylococcus aureus Bacteremia; A Retrospective Chart Review
Authors: Aldred Bruce M , Drekonja Dimitri M 
Published: January 2021

Abstract

Background
Evaluation for endocarditis is an essential step in the management of patients with Staphylococcus aureus bacteremia (SAB). A common approach, consistent with preeminent national guidelines, is to perform transthoracic echocardiography (TTE) followed by transesophageal echocardiography (TEE) in the majority of patients with SAB. It is unclear how often patient management decisions are influenced by the results of TTE versus TEE.

Methods
This retrospective chart review of 180 subjects evaluated adult veterans at a single large Veterans Affairs medical center who had SAB and completed both TTE and TEE. Institution-specific guidelines at this medical center, which were in place throughout the study time period, recommended completion of both TTE and TEE for all patients diagnosed with SAB if able to tolerate both studies. The timing of key patient-management decisions was correlated to the timing of each patient’s TTE and TEE. It was then inferred whether each decision would have been informed by TTE alone versus TTE plus subsequent TEE. Management decisions included: initiation of synergistic antibiotics, documentation of antibiotic treatment duration, consultation of specialists such as Cardiology or Cardiac Surgery, and performance of valve surgery.

Results
Preliminary results show that management decisions were typically not performed until patients had undergone both echocardiography studies. In 18% of patients, management was deemed to be influenced in any capacity following TTE, compared to 91% following both TTE and TEE.

Conclusion
Our findings question the utility of performing a TTE in patients with SAB who are planned to also undergo a subsequent TEE.

Disclosures
All Authors: No reported disclosures