bluuebunny/crossref_metadata_2025_split huggingface dataset:
1119. Assessment of Vancomycin Pharmacokinetic Parameters in Pediatric Patients After Liver Transplantation
Authors: Morales Ronaldo , Juodinis Vanessa D , de Souza Daniela Carla , Jorge Santos Silvia Regina C 
Published: December 2021

Abstract

Background
Vancomycin is largely prescribed to treat gram-positive bacterial infections in pediatric patients after liver transplantation with the same empirical doses prescribed in other critical conditions due to the absence of pharmacokinetic studies in this population. The objective of this investigation was to describe the vancomycin pharmacokinetic parameters and to assess the vancomycin percentage of target attainment with empirical regimen.

Methods
Prospective and longitudinal study with pediatric post-liver transplantation patients who received at least 48 hours of vancomycin between January 2020 and May 2021. Patients with acute or chronic renal failure or receiving renal replacement therapy were excluded. Vancomycin therapy started with 40-60mg/kg daily, one-hour infusion. The pharmacokinetic parameters were determined by one-compartment model with first-order kinetics using near steady-state postdistributional peak and trough within the same dosing interval. Therapeutic target was defined as vancomycin 24-hour area under the curve/minimum inhibitory concentration (AUCss0-24/MIC) ≥ 400 and &lt; 600. The study protocol was approved by the local ethics committee.

Results
We included 18 sets of peak/trough serum concentrations obtained from 12 patients. The patients had median age of 11 (interquartile range [IQ] 8-16) months. The found vancomycin clearance, volume of distribution and half-life values were, respectively, 2.1 (IQ 1.4-2.8) mL/kg/min, 0.6 (IQ 0.5-0.7) L/kg and 3.2 (IQ 2.3-4.0) hours. After the initial dose regimen, 5 (42%) patients reached the therapeutic target.

Conclusion
Using the one-compartment model, we evaluate the pharmacokinetic parameters of vancomycin in pediatric patients after liver transplantation. Most of patients did not reach the therapeutic target with empirical regimen, so it is prudent to monitor the exposure to vancomycin directly by AUC/MIC ratio to maximize antimicrobial efficacy.

Disclosures
All Authors: No reported disclosures
1120. Absorption, Metabolism, and Excretion of [14C]-Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) Following a Single Oral Dose in Healthy Male Subjects
Authors: Gupta Vipul K , Maier Gary , Gasink Leanne , Ek Amanda , Fudeman Mary , Srivastava Praveen , Talley Angela 
Published: December 2021

Abstract

Background
Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral prodrug that is converted to tebipenem (TBP), the active moiety, with activity against multidrug-resistant gram-negative pathogens, including extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales. TBP-PI-HBr is the first oral carbapenem intended for treating complicated urinary tract infections and acute pyelonephritis. This study evaluated the absorption, metabolism, and excretion (AME) of TBP-PI-HBr following a single oral dose of [14C]-TBP-PI-HBr to healthy males and characterized metabolites in plasma, urine, and feces.

Methods
This was a Phase 1, open-label, single-dose study in healthy subjects. Study drug was provided as radiolabeled and non-radiolabeled active pharmaceutical ingredient containing approximately 150 μCi of [14C]-TBP-PI-HBr. On Day 1, each subject received a 600 mg dose of TBP-PI-HBr. administered with 240 mL of water and fasted overnight for at least 10 hours. Blood samples were collected to determine TBP concentrations (whole blood), total radioactivity (whole blood and plasma), and metabolite profiling and identification were determined from plasma, urine, and feces. For mass balance, total radioactivity derived from urine and feces collections were determined. PK parameters were calculated using noncompartmental methods.

Results
Total radioactivity in plasma and whole blood decreased rapidly with geometric mean t½ values of 6.0 hours and 3.5 hours, respectively and Tmax of 1 hour. The cumulative mean recovery of radioactivity was 38.7% in urine and 44.6% in feces. Most of the administered radioactivity was recovered in the first 144 hours post dose in urine and feces (80.0%). Six of 8 subjects achieved a mass balance recovery ranging from 80.1% to 85.0%. The TBP plasma to total radioactivity ratio of 0.536 indicated that other metabolites contribute to the total radioactivity AUC in plasma. Metabolite profiling and identification results indicated that TBP was the major component in plasma and urine. The inactive ring open metabolite of TBP (LJC 11,562) was also found in plasma
( &gt;10%), urine (5.27%), and feces ( &gt;10%) as a secondary metabolite.

Conclusion
This study adequately characterized the AME of TBP-PI-HBr in humans.

Disclosures
Vipul K. Gupta, Ph.D., Spero Therapeutics (Employee, Shareholder) Gary Maier, PhD, Spero Therapeutics, Inc. (Consultant) Leanne Gasink, MD, Spero Therapeutics, Inc. (Consultant) Amanda Ek, MS, Spero Therapeutics, Inc. (Employee) Mary Fudeman, BA, MBA, Spero Therapeutics, Inc. (Employee) Praveen Srivastava, MS, BS, Spero Therapeutics, Inc. (Employee) Angela Talley, MD, Spero Therapeutics, Inc. (Employee)
1123. Appropriateness of Antibiotic Prescribing Through the COVID-19 Pandemic and Associated Telehealth Visits
Authors: Wattles Bethany A , Stahl James A , Jawad Kahir S , Feygin Yana , Kong Maiying , Vidwan Navjyot , Stevenson Michelle D , Smith Michael J 
Published: December 2021

Abstract

Background
The COVID-19 pandemic and resulting mitigation strategies have impacted rates of outpatient infections and delivery of care to pediatric patients. Virtual healthcare was rapidly implemented but much is unknown about the quality of care provided in telehealth visits. We sought to describe changes in visits throughout the pandemic and evaluate the appropriateness of antibiotic prescribing.

Methods
We utilized EHR data from a large health care system that provides primary care via pediatric, family medicine, and urgent care clinics. We included outpatient visits from 1/1/19 - 4/30/21 for children &lt; 20 years. The COVID-19 era was defined as after March 2020. Visits were labeled as virtual according to coded encounter or visit type variables. The appropriateness of antibiotic prescriptions was assigned using a previously published ICD-10 classification scheme that defines each prescription as appropriate, potentially appropriate, or inappropriate (Chua, et al. BMJ, 2019).

Results
There were 805,130 outpatient visits during the study period. The mean rate of antibiotic prescriptions in the pre-pandemic period was 23% (range 17-26% per month) and 11% (range 9-15%) in the COVID-19 era. Mean rates of inappropriate prescribing were 17% (range 14-20% per month) and 20% (range 19-22%), respectively (Figure 1). Coded virtual visits during the COVID-19 era were uncommon (1-2%) with the exception of April and May 2020 (11% and 5%, respectively). During the COVID-19 era, approximately 9% of telehealth visits resulted in antibiotics, compared to 11% of in-person visits (Table 1). Virtual visits had lower rates of inappropriate and appropriate prescribing, but higher rates of potentially appropriate prescribing (Table 1).
Visits and associated antibiotic prescribing in the pre-pandemic and COVID-19 era

Appropriateness of antibiotic prescribing in the COVID-19 era, by visit type

Conclusion
Rates and volume of antibiotic prescribing in outpatient pediatric visits have declined in the COVID-19 era, while rates of inappropriate prescribing have increased slightly. Our study suggests use of telehealth for pediatric visits was minimal and led to higher prescribing rates for “potentially appropriate” indications. This could be explained by a lack of clinical certainty in conditions such as otitis media and pharyngitis in virtual visits.

Disclosures
Bethany A. Wattles, PharmD, MHA, Merck (Grant/Research Support, Research Grant or Support) Yana Feygin, Master of Science, Merck (Grant/Research Support, Research Grant or Support) Michelle D. Stevenson, MD, MS, Merck (Grant/Research Support) Michael J. Smith, MD, M.S.C.E, Merck (Grant/Research Support)Pfizer (Grant/Research Support)
1124. Evaluation of the Use and Impact of the BioFire FilmArray® Respiratory Panel on Diagnosis and Treatment of Pedidatric Respiratory Infections: A Quality Improvement Project
Authors: McVinney Ian , Maples Holly 
Published: December 2021

Abstract

Background
The BioFire FilmArray® Respiratory Panel is a respiratory pathogen PCR that is used to detect the presence of 20 different infectious organisms that cause respiratory illness. Young children are prone to viral upper respiratory illness and represent an age group most likely to receive an antibiotic. As rapid diagnostics evolve, utilizing these tools within antimicrobial stewardship programs to improve utilization of antimicrobials is ideal. The purpose of this study was to assess how the BioFire FilmArray® Respiratory Panel is being used in practice and optimize its use in a large, free-standing, academic children’s hospital.

Methods
Retrospective chart review evaluating all patients (inpatient and outpatient) that received the BioFire FilmArray® Respiratory Panel from December 1, to December 10, 2019. Patients were evaluated based on where the panel was administered, results of the panel, results of other cultures, utilization of antibiotics, and overall hospital course. Data was collected from the electronic medical record and entered into a REDCap database and then analyzed descriptively.

Results
151 patients were included with an average age of 2.6 years with 78 (51.7%) being &lt; 1 year of age. 105 (70%) were administered in either the clinic or ED. In the &lt; 1 year group, 29 (37%) received antibiotic therapy, with 20 having positive viral panels and 11 had positive bacterial cultures. In the ≥ 1 year of age group, 38 (52%) received antibiotic therapy, with 28 having positive viral panels and 9 had positive bacterial cultures. In the outpatient group, 33/105 (31%) were given empiric antibiotics of which 66% had positive viral panels. In the inpatient group, 28/46 (61%) were given empiric antibiotics of which 68% had positive viral panels.

Conclusion
The BioFire FilmArray® Respiratory Panel was found to be primarily utilized in the young child and outpatient/ED setting. With approximately 67% of children who received empiric antibiotics having a positive viral panel, and the majority of these not having positive bacterial cultures, work can be done to decrease the initiation of empiric antibiotics or earlier discontinuation. Further studies are needed in order to determine the optimal strategy for using the viral panel to de-escalate and escalate antimicrobial therapy in practice.

Disclosures
All Authors: No reported disclosures
1126. Short-Course Therapy and Transition to Enteral Antibiotics for Uncomplicated Bacteremia Due to Enterobacterales Species
Authors: Wardell Hanna , Vaughan-Malloy Ana M , Gidengil Courtney , Velarde Jorge J , Khoury Zana , Yim Ramy , Jones Sarah , Nakamura Mari M , Lamb Gabriella S , Lamb Gabriella S 
Published: December 2021

Abstract

Background
Gram-negative bacteremia historically has been treated with 10-14 days of parenteral antibiotics. However, data supporting this practice are lacking, and recent evidence shows equivalent outcomes for short-course (SC) therapy (7 days) and early (by day 5) conversion to highly bioavailable enteral (PO) antibiotics for Enterobacterales bacteremia.

Methods
Under a QI framework, we used PDSA cycles to reduce treatment duration and increase use of PO levofloxacin or trimethoprim-sulfamethoxazole for uncomplicated Enterobacterales bacteremia among Infectious Diseases (ID) clinicians at a children’s hospital in Boston, MA. We conducted an education session on evidence to support these practices for ID faculty and fellows in October 2020. In December 2020, we implemented standardized recommendations for a 7-day duration and early PO transition for eligible patients (≥ 3-months-old, ≤ 2 days monomicrobial bacteremia, with source control and return to baseline clinical status) that could be inserted automatically into electronic consult notes. In February 2021, we reinforced this practice to ID providers. We collected data before and after these interventions on ID recommendations and on patients’ actual antibiotic management.

Results
From 11/01/20 to 05/31/21, mean recommended treatment decreased from 10.6 to 9.5 days; however, mean duration received was similar (11.2 vs 11.7 days) (Figure 1). The percentage of patients for whom ID recommended PO conversion and in whom transition to PO agents by day 5 occurred increased from 27% to 37.5%.

Figure 1. Change in average duration of antibiotics recommended and received, in days

Conclusion
Education and creation of automated standardized recommendations led to decreased recommended treatment durations and increased PO conversions for Enterobacterales bacteremia, but only modestly. This quality improvement initiative demonstrates the potential benefits of education and electronic documentation tools to facilitate evidence-based practice changes, but also highlights the difficulty in changing practice even amongst ID clinicians. Further PDSA cycles will be targeted at increasing more consistent awareness among a large ID division in addition to other stakeholders.

Disclosures
Gabriella S. Lamb, MD, MPH, Nothing to disclose
132. Evaluation Phage Cocktails in Combination with Ciprofloxacin Against Multidrug-Resistant Pseudomonas aeruginosa Overexpressing MexAB-OprM Efflux Systems
Authors: Holger Dana , Lev Katherine , Bhutani Natasha , Kebriaei Razieh , Morrisette Taylor , Lehman Susan , Alexander Jose , Rybak Michael J 
Published: December 2021

Abstract

Background
Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are increasing in prevalence and cause significant mortality. The MexAB-OprM efflux system confers resistance to a wide range of drugs, including β-lactams, fluoroquinolones, tetracyclines, and macrolides. Obligately lytic bacteriophages (phages) are viruses that infect and kill bacteria. Phage therapy has been suggested as an alternative treatment option in combination with traditional antibiotics. The objective of this study was to determine the ability of a phage cocktail in combination with ciprofloxacin (CIP) to improve bacterial killing and/or prevent the emergence of phage resistance in MDR P. aeruginosa.

Methods
Initial bacterial susceptibility to phage was evaluated with three newly isolated phages (phages EM, LL, and A6) against ten clinical MDR P. aeruginosa isolates. Theoretical multiplicity of infection (tMOI) optimization was performed with two phages with the broadest initial susceptibility (tMOI: 1.0 chosen for further analysis). A preliminary evaluation was performed with P. aeruginosa R9316 (carbapenem-resistant clinical strain with MexAB-OprM overexpression, as determined previously by quantitative real-time PCR). Synergy for phage cocktail combinations (≥ 2-log10 CFU/mL kill compared to most effective single agent at 24 h), bactericidal activity for all samples (≥ 3-log10 CFU/mL reduction at 24 h compared to starting inoculum), and phage resistance development were evaluated in time kill analyses (TKA).

Results
R9316 is a MDR P. aeruginosa isolate with a CIP MIC of 2 mg/L. Phage cocktails as monotherapy had little impact on bacterial eradication (reduction: 1.19 log10 CFU/mL). However, the addition of CIP to phage cocktails of EM and LL phages led to synergistic and bactericidal effects (reduction: 3.92 log10 CFU/mL). Furthermore, phage resistance was observed in the phage monotherapy regimens. Whereas the addition of CIP was shown to prevent the emergence of phage resistance in some regimens.

Conclusion
Our results show synergistic activity and prevention of phage resistance with phage cocktail-antibiotic combinations against MDR P. aeruginosa. Further research is needed to determine the impact of phage cocktail therapy on additional strains and clinical outcomes.

Disclosures
Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)
1128. Antibiotic Stewardship in Nonoperative Management of Perforated Appendicitis: Oral Antibiotics Are an Alternative
Authors: Bucayu Robert F , Galvis Alvaro , John Rebecca , Nieves Delma 
Published: December 2021

Abstract

Background
Standard of care of nonoperative appendicitis patients involves ongoing antibiotic therapy. Yet, there is variability regarding the decision to continue outpatient parenteral antibiotic treatment (OPAT) or transition to oral (PO) antibiotics. We review antibiotic susceptibility patterns aiming to help guide antibiotic choice and reduce the need for OPAT.

Methods
Single center retrospective study reviewing pediatric inpatients who underwent nonoperative management of perforated appendicitis with cultures obtained during drainage by Interventional Radiology (IR). We reviewed age, ethnicity, hospitalization length, antibiotic choice, route and duration, and culture data.

Results
Forty-six patients underwent nonoperative medical management for appendicitis (23[50%] 5-12 year olds (yo); 16[35%] 12-&lt; 18yo; 23[50%] Latino;13[28%] White, 11[24%] Other; 5[11%] Asian; 1[2%] Black). Thirty-eight [83%] patients went home on OPAT, 6[13%] on PO, and 2[4%] completed therapy while inpatient. Time from admission to IR drainage was 1.9 ± 2.8 days (34[75%] within 24 hours of admission, 3[8%] within 24-48, and 2[5%] within 48-72). Duration of hospital stay was 9.7 ± 4 days (PO) and 5.9 ± 2.7 days (OPAT). Duration on antibiotics was 20 ± 9.3 (PO) and 18.4 ± 4.9 days (OPAT). Labs on admission and discharge are compared in Table 1. Eight [17%] patients were readmitted due to complications, 38[83%] went home with a drain, and 20[43%] had a fecalith on CT scan. Based on culture susceptibilities of the 38 OPAT patients, 29[76%] had oral antibiotics as an option. The three most common organisms in those sent home on OPAT included Enterococcus faecalis (38[100%]), Bacteroides spp (33[87%]) and Escherichia coli (27[71%]) (Figure 1). All patients who grew Pseudomonas aeruginosa had a PO option; similarly with 93% of E. coli, 81% of α-hemolytic Streptococcus spp, and 76% of E. faecalis.

Conclusion
Nearly 80% of patients sent home on OPAT had PO antibiotic regimens options based on the culture results & susceptibility profiles. This data indicates that using cultures and susceptibility data can help guide antibiotic management, significantly reducing PICC line placement and likely reduce healthcare costs and complications associated with central lines.

Disclosures
All Authors: No reported disclosures
1129. Outpatient Prescribing During the COVID-19 Pandemic
Authors: Moorthy Ganga , Zhao Congwen , Smith Michael J 
Published: December 2021

Abstract

Background
The Joint Commission requires ambulatory healthcare systems to collect, analyze and report antimicrobial prescribing data. Duke University Health System (DUHS) piloted a dashboard to capture outpatient prescribing for pediatric patients with URI. Implementation in 2020 allowed for an assessment of antibiotic prescribing during the pandemic.

Methods
We included patients 0 - &lt; 19 years seen at DUHS for URI and pharyngitis from 1/1/2019 -2/21/2021. Patient characteristics included: age, sex, race, ethnicity, Pediatric Medical Complexity Algorithm (PMCA) score and insurance status (public versus private). Provider characteristics included: type (physician, NP, PA) and specialty (pediatrics, family medicine, internal medicine, other). We compared pre- and post-COVID ( March 1, 2020) prescribing and prescribing during telehealth versus in-person visits. A logistic regression model was used to identify factors independently associated with antibiotic prescribing.

Results
62,447 children were seen during the study period, 29% of whom received an antibiotic. Amoxicillin was the most commonly prescribed antibiotic (64.4%), followed by cefdinir (11%) amoxicillin-clavulanic acid (10%) and azithromycin (8%). Factors associated with antibiotic prescribing are shown in Table 1. White race, private insurance, visits with nurse practitioners and visits with non-pediatric providers were associated with high prescribing. Higher PMCA scores, indicating greater medical complexity, were associated with decreased likelihood of prescribing. Although the total number of outpatient visits plummeted during the COVID period, rates of prescribing only decreased mildly from 31% to 25% (Figure 1).
Table 1. Factors Associated with Antibiotic Prescribing in Logistic Regression Model

Conclusion
Outpatient prescribing was associated with multiple patient and provider characteristics. Similar to other studies, white race, private insurance, and visits with non-physician, non-pediatric providers were associated with antibiotic prescription. Despite a large decrease in the number of outpatient visits during the pandemic, rates of prescribing for URI decreased minimally. A better understanding of factors associated with antibiotic prescribing during the pandemic may identify priority targets for outpatient stewardship as mitigation strategies are relaxed.

Disclosures
Michael J. Smith, MD, M.S.C.E, Merck (Grant/Research Support)Pfizer (Grant/Research Support)