bluuebunny/crossref_metadata_2025_split huggingface dataset:
621. Identifying Quality-Improvement Interventions to Improve Inpatient Intravenous Vancomycin Safety at an Academic Medical Center
Authors: Christensen Sean , Benefield Russell J 
Published: December 2021

Abstract

Background
The reported incidence of intravenous (IV) vancomycin-associated acute kidney injury (AKI) is highly variable. The primary purpose of this study was to determine the baseline rate of IV vancomycin-associated AKI at the University of Utah Hospital (UUH) and Huntsman Cancer Institute (HCI) with the goal of identifying areas of focus for future quality improvement (QI) initiatives.

Methods
This was a retrospective descriptive study of patients ≥ 18 years old, hospitalized at UUH or HCI, who received at least daily scheduled doses of IV vancomycin for ≥ 72 hours between November 1, 2018 and October 31, 2019. AKI was defined using the serum creatinine (SCr) aspect of the AKIN criteria. Variables assessed for association with AKI included demographic characteristics, hospital and unit where vancomycin was initiated, duration of therapy, administration method, and concomitant nephrotoxic medications. Multivariable logistic regression was used to identify variables independently associated with AKI as potential QI interventions.

Results
One thousand eighty-six patients were included. Baseline patient characteristics are listed in Table 1. Throughout our system, 19.7% of patients experienced an AKI while receiving vancomycin. Univariate comparisons are listed in Table 1. Variables independently associated with AKI on multivariable analysis included total body weight (HR 1.02, 95% CI [1.01-1.03]), concomitant administration of calcineurin inhibitors or vasopressors (HR 1.97, 95% CI [1.18-3.29] and HR 1.68, 85% CI [1.07-2.64] respectively), duration of vancomycin therapy (HR, 1.04, 95% CI [1.02-1.06]), and administration in specific units (see Table 1). Administration of vancomycin by continuous infusion showed a protective effect (HR 0.13, 95% CI [0.02-1.12]) as did baseline SCr and total daily dose of vancomycin (HR 0.76, 95% CI [0.61-0.94] and HR 0.63, 95% CI [0.51-0.78] respectively); the latter two are likely a reflection of the study design. The median hospital length of stay in days was longer in individuals experiencing an AKI (19 vs 10, p &lt; 0.0001).
Table 1. Univariate and Multivariate Associations with Vancomycin-Associated Acute Kidney Injury

aFor continuous variables, the HR reported is for each unit increase
Table 1. (Continued) Univariate and Multivariate Associations with Vancomycin-Associated Acute Kidney Injury

aFor continuous variables, the HR reported is for each unit increase

Conclusion
Several variables associated with vancomycin-associated AKI within our health system were identified. Future QI interventions to improve vancomycin safety will be pursued.

Disclosures
Russell J. Benefield, PharmD, Paratek Pharmaceuticals (Grant/Research Support)
622. Evaluation of Vascular Access Device Selection in Patients Discharged on Outpatient Parenteral Antimicrobial Therapy
Authors: Hu Jessica , Dutcher Lauren , Athans Vasilios , Binkley Shawn , Harris Justin , Patel Sonal , Saw Stephen , Lee Tiffany 
Published: December 2021

Abstract

Background
Selection of a vascular access device (VAD) is an important consideration for patients receiving outpatient parenteral antimicrobial therapy (OPAT). Midline catheters (MC) and peripherally inserted central catheters (PICC) are the most commonly placed VADs, with the former recommended by national guidelines to be used for durations no longer than two weeks. These recommendations, however, are based on limited data from heterogeneous populations. As such, we aim to further characterize VAD-associated complications specifically in patients receiving antimicrobials.

Methods
We conducted a retrospective cohort study that included adult patients discharged on OPAT with a newly inserted MC or PICC between January 2020 and August 2020. Patients with non-OPAT VAD indications were excluded. The primary outcome was the incidence of VAD-associated complications, which was further assessed by type and severity. The secondary outcome was time to complication. Multivariable Poisson regression was used to assess the association between VAD type and incidence of VAD-associated complications.

Results
A total of 190 encounters from 181 patients were included for analysis. Baseline demographics are detailed in Table 1. Despite a higher number of complications in the PICC group, rates per 1000 VAD days were not significantly different between VAD types (Table 2). Median time to first complication was 17 days in the overall cohort. Multivariable regression analysis showed those with a dermatologic history had a four-fold increased risk for VAD-associated complications (Table 3). VAD type was not independently associated with the risk of developing a complication.

Conclusion
Our results suggest that the development of VAD-associated complications was strongly associated with patients’ dermatologic history. To our knowledge, dermatologic history has not been previously identified as a risk factor for VAD-associated complications. Thorough assessment of patient-specific risk factors can inform optimal VAD selection for patients discharged on OPAT. Further studies are needed to assess the safety of MC for extended OPAT use.

Disclosures
All Authors: No reported disclosures
624. Perceptions of Telemedicine among Infectious Disease Outpatient Providers during the COVID-19 Pandemic
Authors: Pillai Prishanya , Carvajal Karen , Winbush Angelina , Palli Rohith , Louie Ted 
Published: December 2021

Abstract

Background
Access to infectious disease (ID) providers has been heavily impacted by COVID-19. Telemedicine (TM) has been viewed as a promising solution to the challenges in care delivery posed by this pandemic. However, perceptions of TM among ID providers remain unclear. This study investigated the impact of TM on outpatient ID during the COVID-19 pandemic, efficacy of TM in ID clinics, which clinical conditions within ID that TM may be best suited for, and influences on provider attitudes toward TM.

Methods
We conducted online surveys of outpatient ID providers via the IDSA Idea Exchange and by reaching out to large ID private practices via email. Data was collected October 2020 - April 2021 and recorded through REDCap (Research and Electronic Data Capture). Associations were calculated using Hmisc in R and p-values adjusted using B-H. Missing values were imputed by median.

Results
108 respondents completed the survey. 70.4% were attendings, 63% were under age 50, and 65.7% practiced in academic centers. 55.7% somewhat or strongly agreed there was a decline in outpatient visits. A median of 40% of outpatient visits during COVID were reported to be conducted via TM, divided equally between telephone and televideo (TV). 71.9% of providers somewhat or strongly agreed that TV visits were more effective than telephone visits. Reasons cited for TM as less effective than in person visits included lessened ability to examine the patient, diminished rapport, and inability to perform labwork. 85.2% somewhat or strongly agreed that patients responded favorably to TM. 89.8% of providers somewhat or strongly agreed they will continue to conduct TM visits when appropriate after COVID-19. Plans to continue TM after COVID were significantly associated with perceptions of patient response to TM. Respondents mentioned specific problems less suited to TM: new HIV patients, skin, soft tissue, and joint infections, fever, abdominal pain, transplant evaluations, rash, and wounds.

Conclusion
The majority of providers felt their patients responded favorably to TM. Most providers plan to conduct TM visits after COVID-19. These plans are associated with views of patient response and comparability to other visit types. Specific diagnoses were cited as better suited for TM.

Disclosures
All Authors: No reported disclosures
625. The Hidden Cost of Dalbavancin: OPAT-RN Time Spent on Coordination for Patients with Substance Use Disorder
Authors: Douglass Alyse , Mayer Heather , Young Kathleen , Streifel Amber C , Makadia Jina , Lewis James , Sikka Monica K 
Published: December 2021

Abstract

Background
The use of dalbavancin (DAL) enhances the management of serious gram-positive infections in people with substance use disorder (SUD) by eliminating the need for central lines, weekly lab monitoring, and may decrease length of hospitalizations. Though administered weekly, care coordination for DAL is often complex, due to variable access to resources, insurance variation and treatment settings. Our institution uses OPTIONS-DC, a multi-disciplinary discharge planning conference facilitated by an outpatient parenteral antimicrobial therapy (OPAT) registered nurse (RN) to determine safe treatment plans while emphasizing patient preference for hospitalized patients with SUD and serious infections. When DAL is selected for treatment, patients are enrolled in the RN-led OPAT program for coordination and monitoring. DAL has been shown to result in monetary savings but these estimates have yet to incorporate the true cost of coordination.

Methods
We conducted a retrospective chart review of OPAT staff interventions required to coordinate DAL doses for patients with SUD (identified via ICD-10 code or chart notes). Additionally, we recorded in real time, the amount of time spent per intervention over a one month period for 7 additional patients.

Results
53 courses of DAL in patients with SUD were included with a variety of dosing regimens and treatment settings (Table 1). 41 (77%) patients endorsed IV substance use. 68% of patients received DAL for osteomyelitis or endocarditis. The majority were insured by Oregon Medicaid (70%). The number of RN interventions per course averaged 3.35 with the most common being coordinating with patients and vendors (Table 2). The average time spent per patient course during a one-month sample was 39.4 minutes (range 15 – 58 minutes). The most time-consuming interventions were conducting the OPTIONS-DC conferences and attempting to reach patients after hospital discharge. Readmission for adverse effects or infection occurred for 4 (8%) patients.

Conclusion
The OPAT-RN time required to coordinate outpatient DAL for patients with SUD is substantial. This enhanced coordination allows for potential cost savings to health systems.

Disclosures
Amber C. Streifel, PharmD, BCPS, Melinta (Advisor or Review Panel member) Monica K. Sikka, MD, FG2 (Scientific Research Study Investigator)
626. The Efficacy and Safety of Maintenance with Doravirine Plus Two NRTIs after Initial Suppression in Adults with HIV-1 in the DRIVE-FORWARD Clinical Trial: Results from the Study Extension through 192 Weeks
Authors: Cahn Pedro , Molina Jean-michel , Lombaard Johan , Squires Kathleen , Kumar Sushma , Wan Hong , Teal Valerie , Asante-Appiah Ernest , Sklar Peter , Martin Elizabeth A , Lahoulou Rima 
Published: December 2021

Abstract

Background
DRIVE-FORWARD is a phase 3 trial with a completed double-blind period comparing doravirine (DOR) 100 mg with ritonavir-boosted darunavir (DRV/r) 800/100 mg, both administered with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs; tenofovir and emtricitabine, or abacavir and lamivudine), and an ongoing open-label extension. At Week (W) 48, DOR demonstrated non-inferior efficacy to DRV/r, with a superior lipid profile. Those results were sustained at W96. Here we present efficacy and safety results through W192.

Methods
Participants who completed the 96-week double-blind phase and met inclusion criteria were eligible to receive open-label DOR plus two NRTIs in a 96-week extension. Efficacy and safety at W192 were assessed in two groups: participants initially randomized to DOR and maintained on DOR (n=259) and those who switched from DRV/r to DOR at W96 (n=233).

Results
HIV-1 RNA &lt; 50 copies/mL were maintained through W192 in 81.1% of participants who continued DOR and 80.7% of those who switched from DRV/r to DOR. The mean increase in CD4 T-cell counts from W96 to W192 was similar for participants maintained on DOR (47 cells/mm3) and those switched from DRV/r (53 cells/mm3). Protocol-defined virologic failure occurred in 3.1% and 5.6% of participants maintained on DOR and switched from DRV/r, respectively, and development of genotypic resistance was low in both groups (Table 1). Discontinuation due to adverse events was also low (Table 1). Fasting LDL-cholesterol, non-HDL-cholesterol, and triglycerides showed minimal increase in participants maintained on DOR and were reduced in those switched from DRV/r to DOR (Table 1). Participants maintained on DOR had minimal weight gain after W96 (median 1 kg), and a small increase overall (median 1.9 kg, Day 1 through W192); participants who switched to DOR had a small increase after W96 (median 1.5 kg), similar to the median weight gain in the base study (DOR 1.8 kg; DRV/r 0.7 kg).

Conclusion
Among participants who continued DOR in the DRIVE-FORWARD open-label extension, virologic suppression and favorable safety were maintained for an additional 96 weeks. Participants who switched from DRV/r to DOR maintained virologic suppression and demonstrated favorable safety for 96 weeks.

Disclosures
Pedro Cahn, MD, PHD, Merck (Advisor or Review Panel member)ViiV Healthcare (Grant/Research Support, Advisor or Review Panel member) Kathleen Squires, MD, Merck (Employee) Sushma Kumar, PhD, Merck (Employee) Hong Wan, PhD, Merck (Employee) Valerie Teal, MS, Merck (Employee) Ernest Asante-Appiah, PhD, Merck (Employee) Peter Sklar, MD, Merck (Employee) Elizabeth A. Martin, DO, MPH, MBA, Merck (Employee) Rima Lahoulou, n/a, Merck (Employee)
628. Pharmacokinetics, Safety and Tolerability of Co-administration of Nacubactam and β-lactams after Multiple Doses in Japanese Healthy Subjects
Authors: Sato Hiroki , Morita Jun , Miura Tatsuo , Sumiya Masayo , Takaya Risako , Kondo Kenichiro 
Published: December 2021

Abstract

Background
Increase of carbapenem-resistant Enterobacterales (CRE) is a serious problem in the clinical setting and drugs which can treat patients with CRE are still limited. Nacubactam (OP0595) is a novel diazabicyclooctane-type β-lactamase inhibitor and being developed as a standalone drug to be co-administered with cefepime or aztreonam.

Methods
A randomized, double-blind multiple dose study of nacubactam in co-administration with cefepime (Cohort 1) or aztreonam (Cohort 2) in Japanese healthy subjects was performed to assess pharmacokinetics, safety, and tolerability of co-administrations of nacubactam and cefepime or aztreonam. In each cohort, 6 subjects received 2 g of nacubactam and 2 g of concomitant drug (cefepime or aztreonam) and 2 subjects received placebo (saline) intravenously over 60 minutes, three times daily every 8 hours for 7 days. Plasma samples were collected and concentrations of each drug were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and the evaluation of changes from baseline in safety laboratory test results, 12-lead electrocardiograms (ECGs), vital signs, and physical examinations.

Results
Profiles of Cmax, tmax, AUC0-8, AUC0-∞ and t1/2 for nacubactam, cefepime and aztreonam are summarized in Table 1. Summary of Ctrough for nacubactam, cefepime and aztreonam are summarized in Table 2. Plasma concentrations of nacubactam, cefepime and aztreonam reached the steady-state by Day 4, and the mean accumulation ratios of Cmax and AUC0-8 on Day 7 to those of Day 1 were in the range of 0.91 to 1.10. As for the safety, no serious adverse event was observed in this study. There was 1 TEAE (seborrhoeic dermatitis) leading to the discontinuation in 1 subject in nacubactam/cefepime group, but it was judged as “Not related to study drug”.
Table 1. PK profiles of nacubactam and concomitant drugs on Day 1 and Day 7

Table 2. Summary of Ctrough of nacubactam and concomitant drugs

Conclusion
In conclusion, no remarkable change in pharmacokinetics was observed in each drug with multiple concomitant administration for 7 days and safety and tolerability of co-administrations of nacubactam and cefepime or aztreonam were confirmed. Based on these results, nacubactam is currently under further development.

Disclosures
All Authors: No reported disclosures
637. Treatment Outcomes in Secondary Analysis Populations of Adult Patients the ALLIUM Phase 3 study Comparing Cefepime-Enmetazobactam to Piperacillin-Tazobactam for Complicated Urinary Tract Infections (cUTI) or Acute Pyelonephritis (AP)
Authors: Kaye Keith S , Belley Adam , Barth Philip , Lahlou Omar , Velicitat Patrick 
Published: December 2021

Abstract

Background
Superior treatment outcomes were observed with the β-lactam/β-lactamase inhibitor combination of cefepime-enmetazobactam (FPE) compared to piperacillin-tazobactam (PTZ) in the primary efficacy population (m-MITT) of the ALLIUM phase 3 study of adult patients with cUTI/AP. We present here the outcomes in the microbiologically evaluable (ME) and ME+Resistant (ME+R) populations.

Methods
1034 cUTI/AP patients randomized 1:1 in a double-blind, multicenter trial received either 2 g cefepime/0.5 g enmetazobactam or 4 g piperacillin/0.5 g tazobactam q8h by 2h infusion for 7 to 14 days. Patients in m-MITT had a Gram-negative urinary baseline pathogen (BP) at &gt;105 CFU/ml with FPE MIC ≤8 µg/ml and PTZ MIC ≤64 µg/ml. ME included patients in m-MITT who received ≥15 consecutive doses of study drug or were classified as clinical failures after receiving ≥9 doses; had a clinical assessment at test-of-cure (TOC) unless clinical failure occurred earlier; did not receive concomitant antibiotics with a non-study agent; and did not have any other protocol violation. ME+R included patients in ME along with those who had BP resistant to either FPE (MIC &gt;8 µg/ml) or PTZ (MIC &gt;64 µg/ml), or a missing MIC value. Overall success was the composite of clinical cure and microbiological eradication (&lt; 103 CFU/ml in urine). Two-sided 95% confidence interval (CI) were computed using the stratified Newcombe method.

Results
In the ME population, superiority in overall success of FPE (87.0%; 268/308) compared to PTZ (65.4%; 195/298) was demonstrated as the lower bound of the CI (16.6%) of the treatment difference (TD; 23.3%) was greater than 0 (Table). Higher rates of microbiological eradication with FPE contributed to the superior treatment outcomes. In the ME+R population in which BP susceptibility was not an exclusion criterion, favorable outcomes with FPE in overall success (TD 21.6%; 95% CI [15.3, 27.8]) and microbiological eradication (TD 21.0%; 95% CI [14.8, 27.0]) were also observed.

Conclusion
The confirmation of superior treatment outcomes with FPE in the ME and ME+R populations supports the robustness of the corresponding superiority observed in adult cUTI/AP patients in m-MITT.

Disclosures
Adam Belley, PhD, Allecra Therapeutics SAS (Consultant) Philip Barth, MD, Allecra Therapeutics SAS (Consultant) Omar Lahlou, PhD, Allecra Therapeutics SAS (Employee) Patrick Velicitat, MD, Allecra Therapeutics SAS (Employee)
641. Clinical Predictors of Hospital-Acquired Bloodstream Infections
Authors: Sheth Radhika , Bhatia Mehakmeet , Kak Vivek 
Published: December 2021

Abstract

Background
Hospital-acquired bloodstream infections (HABSI) are associated with increased mortality and decreased hospital quality metrics. This has led to an increased focus on blood culture stewardship. Little data exists regarding predictive factors of bacteremia in hospitalized patients. We aim to determine what clinical characteristics in patients were predictive of HABSI.

Methods
This is a retrospective case-control study of 540 patients with positive blood cultures admitted to our health system between September 1, 2017, to April 1, 2020. Electronic medical records of patients with positive blood cultures were independently reviewed to determine contamination versus true bacteremia. We looked at different clinical parameters and laboratory investigations within 24 hours of drawing blood cultures. Clinical variables were age ≥ 60 years, heart rate ≥ 90/minute, systolic blood pressure ≤ 90 mmHg or use of a vasopressor, oral temperature &gt; 38°Celsius (100.4°Fahrenheit), white blood cells (WBC) count ≥12,000/µL, lymphocytes ≤ 1000/mm3, platelets &lt; 150,000 /µL, and creatinine &gt;2.0 mg/dL. Stepwise logistic regression analysis was used for predictive statistical model development.

Results
In a cohort of 481 patients with hospital-acquired bacteremia, 350 cases had true bacteremia and 131 cases were contaminated blood cultures. Stepwise regression analysis showed that white blood cell (WBC) count ≥ 12,000 cells/µL, lymphocyte count ≤ 1000/mm3, creatinine &gt; 2.0 mg/dL, and oral temperature &gt; 38°C (100.4°F) were associated with HABSI (R-square= 0.06, p value= 0.002).

Conclusion
Our findings suggest that WBC count, lymphocyte count, creatinine, and oral temperature together can be used to develop appropriate blood culture stewardship models in the inpatient setting. This may help minimize unnecessary blood cultures.

Disclosures
All Authors: No reported disclosures
642. Facility Reported vs. CLSI MIC Breakpoint Comparison of Carbapenem Non-susceptible (Carb-NS) Enterobacteriaceae (ENT) from 2016-2019: A Multicenter Evaluation
Authors: Gupta Vikas , Yu Kalvin , Pogue Jason M , Weeks Janet , Clancy Cornelius J 
Published: December 2021

Abstract

Background
Carbapenem (Carb) minimum inhibitory concentration (MIC) breakpoints were lowered by CLSI in 2010 and recognized by FDA in 2012. Adoption of revised breakpoints is often slow, which may lead to under-reporting of Carb non-susceptibility (NS) by facilities. We compare facility-reported rates of Carb-NS ENT to the CLSI MIC breakpoints for a large nationwide collection of isolates in the United States (US) from 2016-2019.

Methods
All adults with a positive non-contaminant ENT culture (first isolate of a species per 30-day period from blood, respiratory, urine, skin/wound, intra-abdominal, or other) in ambulatory/inpatient settings from up to 300 US hospitals from 2016-2019 were evaluated (BD Insights Research Database). Facility-reported Carb-NS was defined as: susceptible (S), intermediate (I) or R to ertapenem (ETP), imipenem (IPM), meropenem (MEM) and/or doripenem (DOR) per commercial panels. Where available, MICs were interpreted using CLSI 2010 MIC breakpoints (µg/ml): ≤ 0.5 (S), 1 (I), ≥ 2 (R) for ETP and ≤1 (S), 2 (I), and ≥ 4 (R) for IPM/MEM/DOR. For evaluable ENT isolates we compared susceptibility results as reported by the facility to CLSI MIC breakpoints.

Results
Overall, 77.4% (937,926/1,211,845) and 90.6% (2,157,785/2,381,824) non-duplicate ENT isolates with facility-reported susceptibility results also had interpretable MIC results for ETP and IPM/MEM/DOR, respectively (Tables). ETP S rates were 99.3% and 99.1% as reported by facilities and using CLSI criteria, respectively. S rates of other Carbs were 98.9% and 98.4% by facility reporting and CLSI criteria, respectively. Systematic application of CLSI breakpoints under-reported EPT-I and –R isolates by 24.2% and 16.4%, respectively, and identification of IPM/MEM/DOR-I and –R isolates by 31.3% and 22.7%, respectively.

Conclusion
Systematic application of CLSI breakpoints in 2016-19 would have had minimal impact on ENT S rates in the US. However, facility reporting failed to identify 18.8% of ETP I or R and 26.5% of IPM/MEM/DOR I or R isolates. The clinical implications of this observation are unknown. Facilities should know their local epidemiology, decide if under-reporting might be an issue, and assess if there is any impact on their patients.

Disclosures
Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder) Kalvin Yu, MD, BD (Employee) Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Janet Weeks, PhD, Becton, Dickinson and Company (Employee) Cornelius J. Clancy, MD, Merck (Grant/Research Support)