bluuebunny/crossref_metadata_2025 huggingface dataset:
1118. Population Pharmacokinetics of Contezolid Acefosamil and Contezolid – Rationale for a Safe and Effective Loading Dose Regimen
Authors: Bulitta Jürgen B , Hafkin Barry , Fang Edward
Published: December 2021

Background

Contezolid (CZD) is a novel oral oxazolidnone with comparable activity and potentially improved safety compared to current oxazolidinones. The intravenous (IV) double prodrug contezolid acefosamil (CZDa) is converted via MRX-1352 to active CZD. CZDa paired with CZD holds promise as a safe and effective treatment for serious Gram-positive infections such as those caused by methicillin-resistant Staphylococcus aureus. Sequential therapy with CZDa IV followed by CZD oral (PO) offers flexible treatment options in hospital and outpatient settings for conditions such as diabetic foot infections. We aimed to design a CZDa/CZD dosage regimen leveraging population pharmacokinetic modeling (PopPK).

Methods

PopPK simultaneously fit data from 184 adult subjects. These were 1) plasma concentrations (by LC-MS/MS) of MRX-1352, CZD, and its metabolite MRX-1320 from 66 healthy subjects receiving CZDa (150-2400 mg IV) for up to 10 days, 2) CZD and MRX-1320 concentrations from 44 healthy subjects receiving single CZD PO doses of 400, 800, or 1200 mg with and without food or multiple doses Q12h for up to 28 days, and 3) CZD concentrations from 74 Phase 2 patients receiving CZD 800 mg PO Q12h. PopPK and Monte Carlo simulations were used to optimize CZD exposures.

Results

CZDa was rapidly converted to MRX-1352, which was converted less rapidly to CZD. CZD was well absorbed and food enhanced its bioavailability. For CZD 800 mg PO with food, apparent total clearance of CZD was 13.1 L/h (22% coefficient of variation) in healthy subjects and 14.5 L/h (53% CV) in patients. The apparent volume of distribution at steady-state was 20.5 L. A loading dose of CZDa 2000 mg IV, then CZDa 1000 mg IV Q12h, and followed by CZD 800 mg PO Q12h achieved areas under the curve (AUC) between 75 and 100 mg*h/L (medians; Figure) on all study days. Compared to CZD AUCs, the MRX-1352 AUCs during IV dosing were higher. While the median MRX-1320 AUCs were lower (18 to 48 mg*h/L), some accumulation was predicted in ~5% of subjects.

Conclusion

A loading dose of CZDa 2000 mg IV followed by either CZDa 1000 mg IV or CZD 800 mg PO Q12h was predicted to reliably achieve efficacious CZD exposures on day 1 and maintain those exposures throughout therapy. This regimen will be evaluated in Phase 3 studies in complicated skin infections and diabetic foot infections.

Disclosures

Jürgen B. Bulitta, PhD, MicuRx Pharmaceuticals, Inc. (Consultant) Barry HAFKIN, MD, MicuRx Pharmaceuticals Inc. (Consultant)
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

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 < 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

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

( >10%), urine (5.27%), and feces ( >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

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 < 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

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 < 1 year of age. 105 (70%) were administered in either the clinic or ED. In the < 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

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

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

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-< 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

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 - < 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)
1130. Impact of a New Pediatric Antibiotic Stewardship Program on Ceftriaxone Use at an Academic Medical Center
Authors: Evans Derek , Lanata Piazzon Mariana M , Schomburg Kaitlyn
Published: December 2021

Background

Hoop’s Family Children’s Hospital is a pediatric hospital with 72 beds, nested within Cabell Huntington Hospital. There is an established adult antibiotic stewardship program (ASP), however, since 2014 there has not been a pediatric infectious disease (ID) specialist and no pediatric ASP. With the recent hire of a pediatric ID specialist in Oct 2019 and the formation of a targeted pediatric ASP, we tracked the use of ceftriaxone (CRO) in our facility.

Methods

Starting January 2020, education was provided to pediatric providers in regards to appropriate CRO dosing and clinical indications via email communication. The main goals were to limit 100mg/kg/day dosing to severe infections and reduce CRO use in community-acquired pneumonia. This was sustained through intermittent prospective audits and feedback. A retrospective chart review was done from 2019-2021 for the months of January, April and December of each year. Patients ≤18 years of age who received CRO were included. Dosing, interval frequency, indication, and treatment duration were reviewed. Patients who received a single dose of CRO were excluded.

Results

From Jan 2019 – April 2021, 391 patient charts were reviewed (189 in the pre-intervention period and 202 in the post intervention period). There were no significant differences in age, race/ethnicity and gender in the two study groups. In the pre-intervention period, 86% of patients were prescribed CRO at severe infection dosing vs 33% in the post intervention period (p< 0.0001) (Figure 1). When dosing was paired with indication, only 20% of patients in the pre intervention period had the appropriate dosing per clinical indication compared to 83% in the post intervention period (p< 0.0001) (Figure 2). We also saw that in the pre-intervention period the most common indication for CRO was pneumonia (66%), which decreased to 57% in 2020 and to 35% in 2021 (p< 0.0001) (Figure 3).

Figure 1 describes the percentage of patients receiving ceftriaxone at severe infection dosing. This changed from an average of 86% in the pre-intervention period to 33% in the post-intervention period.

Figure 2 describes the percentage of patients receiving ceftriaxone at the appropriate dosing dependent on the clinical indication provided. This changed from 20% in the pre-intervention period to closer to 90% in the post-intervention period.

Conclusion

Pediatric specific ASP efforts and expertise proved to be crucial in appropriate CRO use in our institution. With a feasible education strategy and targeted prospective audit and feedback, there has been a sustained impact in inappropriate CRO use. This underscores the importance of targeted pediatric ASP efforts in pediatric hospitals within larger adult hospitals.

Disclosures

All Authors: No reported disclosures
1131. You’re Never Too Old for a Time-Out: Implementing Antibiotic Time-Outs on Pediatric Inpatient Teams
Authors: Hayes Catherine , Swartwood Michael J , Zwemer Eric , Doughman Danielle , Mavrogiorgos Nikolaos , Daniels Lindsay M , Wellborn Rebecca , Hill Daniel , Wilson William , Willis Zachary
Published: December 2021

Background

Antibiotic overuse leads to antimicrobial resistance, adverse events, and excess costs. Antibiotic time-outs (ABTOs) offer a structured approach to reevaluate antimicrobial regimens, but implementing and maintaining ABTOs can be challenging. In this project, we built on previous ABTO implementation in adult inpatient units to incorporate ABTOs in pediatrics using quality improvement (QI) methods.

Methods

We identified champions, including attending physicians, residents, nurses, team coordinators, and pharmacists. Following pilot testing, ABTOs began in November 2019 and January 2020 for two general pediatric teams, and in June 2020 in the pediatric ICU (PICU). Patients were eligible for an ABTO if they had been on antibiotics for 36-72 hours. ABTOs were documented in the electronic medical record (EMR) with a structured note template. These notes along with patient antimicrobial regimens were extracted and analyzed using an automated EMR query. Metrics included: (1) Proportion of ABTO-eligible patients with an ABTO; (2) Proportion of ABTOs conducted within goal time frame; (3) Documented plan changes in ABTO (e.g. change IV antibiotics to PO); and (4) Proportion of documented changes completed within 24 hours

Results

To date, there have been 342 pediatric ABTOs over 145 team weeks on the general pediatrics teams and 50 weeks in the PICU, representing 96.9% of eligible patients. 77.8% of ABTOs were completed within the recommended time frame. A majority of ABTOs (67%) resulted in no change to antibiotic regimen, and 18% of patients had already had de-escalation. In 10.5% of patients, the ABTO led to a de-escalation (antibiotics discontinued in 2%, converted from IV to PO in 8.5%). 86.8% of planned changes occurred within 24 hours of ABTO.

Figure 1. Compliance with antibiotic time-outs over time, by week. The green line represents the goal of 80%, and the orange line represents median performance.

Figure 2. Planned changes to antimicrobial regimen documented in antibiotic time-out.

Table 1. Antibiotic time-out performance on participating pediatric services.

Conclusion

This project demonstrates that ABTOs can be implemented across a variety of teams and showed successful spread of an adult-based QI project to pediatrics. ABTOs led to clear de-escalation in 10.5% of cases, with other changes made in 5% of cases. Future directions include continued spread to inpatient teams, development of EMR-based ABTO alerts, comparison of overall antibiotic use and adverse events before and after ABTO implementation, and characterization of antimicrobial optimization prior to ABTO.

Disclosures

All Authors: No reported disclosures
1134. The Effect of Telehealth Antimicrobial Stewardship Program on Antimicrobial Use in a Pediatric Intensive Care Unit
Authors: Alghounaim Mohammad , Abdelmoniem Ahmed , Elseadawy Mohamed , Surour Mohammad , Basuni Mohamed , Papenburg Jesse , Alfraij Abdulla
Published: December 2021

Background

Inappropriate antimicrobial use is common in pediatric intensive care units (PICU). We aimed to evaluate the effect of telehealth antimicrobial stewardship program (ASP) on the rate of PICU antimicrobial use in a center without a local infectious diseases consultation service.

Methods

Aretrospective cohort study was performed between October 1st, 2018 and October 31st, 2020 in Farwaniyah Hospital PICU, a 20-bed unit. All pediatric patients who were admitted to PICU and received systemic antimicrobials during the study period were included and followed until hospital discharge. Patients admitted to the PICU prior to the study period but still receiving intensive care during the study period were excluded. Weekly prospective audit and feedback on antimicrobial use was provided starting October 8th, 2019 (post-ASP period) by the ASP team. A pediatric infectious diseases specialist would join ASP rounds remotely. Descriptive analyses and a pre-post intervention comparison of days of therapy (DOT) were used to assess the effectiveness of the ASP intervention

Results

There were 272 and 152 PICU admissions before and after initiation of ASP, respectively. Bronchiolitis and pneumonia were the most common admission diagnoses, together compromising 60.7% and 61.2% pre- and post-ASP. Requirement for respiratory support was higher post-ASP (76.5% vs 91.5%, p< 0.001). Average monthly antimicrobial use decreased from 92.2 (95% CI 74.5 to 100) to 48.5 DOT/1,000 patient-days (95% CI 24.6 to 72.2, P < 0.05) (figure). A decline in DOT was observed across all antibiotic classes, except for ceftriaxone and clarithromycin. No effect on length of PICU stay, hospital length of stay, or mortality was observed. Most (89.7%) ASP recommendations were followed fully or partially changes in antimicrobial days of therapy (DOT)/1,000 patient-days over time. The dashed line represents the start of the antimicrobial stewardship program (ASP)

Conclusion

In settings where infectious diseases services are not available, telehealth stewardship can be effectively implemented and associated with a significant reduction of antimicrobial use.

Disclosures

Jesse Papenburg, MD, AbbVie (Grant/Research Support, Other Financial or Material Support, Personal fees)Medimmune (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)Seegene (Grant/Research Support, Other Financial or Material Support, Personal fees)
1135. The Effect of Penicillin Allergy Labels on Antibiotic Prescribing for Children Diagnosed with Upper Respiratory Tract Infections in Two Primary Care Networks
Authors: Joerger Torsten , Taylor Margaret , Palazzi Debra , Gerber Jeffrey
Published: December 2021

Background

In pediatric inpatient settings, unconfirmed penicillin allergy labels (PALs) are associated with increased broad-spectrum antibiotic use, costs, and adverse events. However, 90% of antibiotics are prescribed in the outpatient setting and 70% of these antibiotics are given for upper respiratory tract infections (URTI.) Little is known about the effect of PALs on antibiotic prescribing in the pediatric outpatient population.

Methods

A retrospective birth cohort was created of children born between January 1st 2010 and June 30th 2020 and seen at one of 91 Texas Children’s Pediatrics or Children’s Hospital of Philadelphia primary care clinics. Children with an ICD10 code for an URTI and an antibiotic prescription were stratified into those with or without a penicillin allergy label at the time of the infection. Rates of second-line and broad-spectrum antibiotic use were compared.

Results

The birth cohort included 334,465 children followed for 1.2 million person-years. An antibiotic was prescribed for 696,782 URTIs and the most common diagnosis was acute otitis media. Children with PALs were significantly more likely to receive second-line antibiotics (OR 35.0, 95% CI 33.9-36.1) and broad-spectrum antibiotics (OR 23.9, 95% CI 23.2-24.8.) Children with PALs received more third generation cephalosporins (60% vs. 15%) and more macrolide antibiotics (25% vs. 3%) than those without a PAL. Overall, 18,015 children (5.4%) acquired a PAL during the study period, which accounted for 23% of all second-line antibiotic prescriptions and 17% of all broad-spectrum antibiotic use for URTIs.

Multivariable logistic regression for receipt of second-line antibiotics for upper respiratory tract infections

Conclusion

PALs are common and account for a substantial proportion of second-line and broad-spectrum antibiotic use in pediatric outpatients treated for URTIs. Efforts to de-label children with PALs are likely to increase first-line antibiotic use and decrease broad-spectrum antibiotic use for URTIs, the most common indication for antibiotic prescribing to children.

Disclosures

Debra Palazzi, MD, MEd, AAP (Other Financial or Material Support, PREP ID Editorial Board, PREP ID Course)AHRQ (Research Grant or Support)Elsevier (Other Financial or Material Support, Royalties for writing and editing chapters)JAMA Pediatrics (Board Member)
1136. Effect of Weekly Antibiotic Rounds as a Core Strategy of the Antimicrobial Stewardship Program on Antibiotic Utilization in a Terciary-care Neonatal Intensive Care Unit, Medellin, Colombia
Authors: Diaz Alejandro Diaz , Mesa-Monsalve Juan Gonzalo , Echavarria-Gil Adriana M , Jimenez Carolina
Published: December 2021

Background

Antibiotics are among the most prescribed drugs in the neonatal intensive care unit (NICU), but frequently are used inappropriately exposing preterm neonates to additional harm. Antibiotic stewardship programs (ASP) have demonstrated impact on antibiotic use in the hospital setting, but implementation in neonatal units is challenging. We sought to determine the effects of weekly antibiotic rounds on overall antibiotic consumption in the NICU.

Methods

Single-center, retrospective observational study. In November 2014, we implemented weekly antibiotic rounds in a 60-bed tertiary-care NICU, led by a pediatric infectious disease physician. Antibiotic therapy decisions were made in collaboration with neonatologists. Data collected included the proportion of patients receiving antibiotics, irrespective of the indication. Multimodal ASP was implemented hospital-wide in 2015. Antibiotic consumption was measured with days of therapy (DOT). Data on costs and in-hospital mortality were obtained from pharmacy and hospital records.

Results

From November 2014 to December 2020, we evaluated 13609 neonates admitted to the NICU during rounds. Of those, 3607 (27%) were receiving at least one antibiotic. Overall, the proportion of patients with antibiotics decreased from 31% to 19% during the study period (p< 0.001). In 2017, an outbreak of neonatal necrotizing enterocolitis (NEC) occurred. Specific countermeasures as well as reinforcement of ASP were implemented. Despite Antibiotic usage by DOT increased in 2017 driven by empiric treatment with piperacillin tazobactam in patients with NEC, overall antibiotic consumption decreased from 254.4 DOT/1000 patient days (PD) to 162.4 DOT/1000 PD (Figure 1). Annual costs from antibiotic prescriptions were US&23,161 in 2015 and decreased to US&12.046 in 2020 saving over US&3,800/year (fig 2a). During the study period, we did not observe an increase in crude in-hospital mortality rate (Figure 2b).

Primary Y axis indicates the proportion of patients with at least one antibiotic prescription during rounds. Secondary Y axis indicates antibiotic consumption by days of therapy metrics.

Antibiotic prescription costs and NICU mortality rates during study period

A. Annual antibiotic prescription costs; B. NICU mortality rate

Conclusion

Weekly antibiotic rounds led to a significant decrease in antibiotic utilization in our NICU. This strategy is relatively simple and low-cost, saves hospital resources and has a large impact on antibiotic use. Hence, its implementation is encouraged as part of successful antimicrobial stewardship programs.

Disclosures

All Authors: No reported disclosures
1138. Utility of Methicillin-resistant Staphylococcus aureus Nares Screening in Hospitalized Children With Acute Infectious Disease Syndromes
Authors: Sands Ashley , Mulvey Nicole , Iacono Denise E , Hagmann Stefan
Published: December 2021

Background

Empirical antibiotic regimens frequently include treatment for methicillin-resistant Staphylococcus aureus (MRSA). Studies in adults with pneumonia support the use of a negative MRSA nares screening (MNS) to help de-escalate antibiotic therapy. Comparable pediatric data in the literature is scarce. We aimed to evaluate the use of MNS for antibiotic de-escalation in hospitalized children (< 18 years) at a tertiary children’s hospital.

Methods

A retrospective chart review was conducted of pediatric inpatients (January 01, 2015 to December 31, 2020) with a presumed infectious diagnosis who had a PCR-based MNS test and a clinical culture (i.e. site of infection or blood) performed as part of their diagnostic work up. Those who were screened >5 days since admission or > 48 hours since start of MRSA-active antimicrobials, and those who had antibiotic treatment withdrawn after 48 hours because of negative cultures were excluded.

Results

A total of 101 children were included with a median age (range) of 2 years (0-17) and about half (n=57, 56.4%) were male. Top three diagnosis groups were skin and soft tissue infections (n=33, 32.7%), toxin-mediated syndromes (n=21, 20.8%), and osteoarticular infections (n=13, 12.9%). Pneumonia accounted for only six (5.9%) patients. The prevalence of nasal MRSA colonization was 6.9% (n=7). The sensitivity of the MNS test to predict a MRSA infection was 42.9% with a specificity of 95.7%. The positive predictive value (PPV) and negative predictive values (NPV) were 42.9% and 95.7%, respectively. In about half (55/95, 57.9%) of patients initiated on anti-MRSA therapy, these agents were discontinued during the admission. A quarter (n=14, 25.5%) were de-escalated based on the negative MNS test alone, and another third (n=21, 38.2%) after negative MNS test and negative culture results became available.

Conclusion

Pediatric providers at this institution have started to use the MNS to help limit anti-MRSA therapy. We noted a high NPV which suggests that MNS may be useful for timely de-escalation of anti-MRSA therapy and thereby a useful antimicrobial stewardship tool for hospitalized children. Prospective studies to evaluate the utility of MNS for the various infectious syndromes are warranted.

Disclosures

All Authors: No reported disclosures
1139. Reducing Collection of Tracheal Aspirate Bacterial Cultures: A Diagnostic Test Stewardship Intervention
Authors: Chiotos Kathleen , Lee Giyoung , Sydney Guy , Wolfe Heather , Blumenthal Jennifer , Stinson Hannah , McGowan Nancy , Harab Julie , Traynor Danielle , Dudhia Aaditya , Piccione Joseph , Burke Jennalyn , Doll Ashley , Keim Garrett , Woods-Hill Charlotte , Jennings Megan , Harris Rebecca , Gerber Jeffrey
Published: December 2021

Background

Tracheal aspirate (TA) bacterial cultures are often collected in mechanically ventilated children to evaluate for ventilator-associated infections (VAI), including tracheitis and pneumonia. However, frequent bacterial colonization of tracheal tubes results in poor specificity of positive TA cultures for distinguishing bacterial infection from colonization, which contributes to antibiotic overuse for VAI. We performed a quality improvement project to reduce collection of TA cultures through implementation of a consensus guideline to standardize culture ordering, and measured its impact on antibiotic use in a tertiary PICU.

Methods

A multidisciplinary team including PICU, pulmonary, and ID clinicians developed the consensus guideline in November 2019-February 2020. The first Plan-Do-Study-Act (PDSA) cycle occurred in August 2020 and included provider education, providing a link to the guideline in the TA culture order, and signs and screensavers highlighting key guideline recommendations. The second PDSA cycle occurred in October-December 2020 and included weekly emails to on service PICU clinicians. Statistical process control charts were used to measure the number of TA cultures collected/100 ventilator days and broad-spectrum antibiotic DOT/100 ventilator days. The number of patients treated for VAI/100 ventilator days and guideline compliance were also measured.

Results

The baseline rate of TA culture collection was 4.58/100 ventilator days. A centerline shift to 3.33 cultures/100 ventilator days occurred in March 2020. Following PDSA 1 and 2 in October 2020, a second downward centerline shift to 2.22 cultures/100 ventilator days occurred (Figure 1). Broad-spectrum antibiotic days of therapy/100 ventilator days decreased in November 2019 coincident with the start of the project, but no further reductions occurred after PDSA 1 and 2 (Figure 2). The number of patients treated for VAI decreased from a baseline of 1.24/100 ventilator days to 0.66/100 ventilator days. Finally, the proportion of TA cultures ordered that were non-compliant with the guideline recommendations was unchanged throughout the study period (Table 1).

Conclusion

A consensus guideline reduced collection of TA cultures, with a modest reduction in the rate of antibiotic treatment for VAI.

Disclosures

All Authors: No reported disclosures
1140. Impact of a Rapid Molecular Bloodstream Diagnostic Test on Optimal Antibiotic Use in Infants
Authors: Norman Savanah , Burton Alexandra , Mumphrey Christy , Joslyn Peter , Cook Gregory
Published: December 2021

Background

Rapid molecular bloodstream diagnostics have been shown to decrease time-to-optimal antibiotic therapy in adult and pediatric patients. The purpose of the study was to compare the time-to-optimal antimicrobial therapy both pre-and post- implementation of rapid diagnostic testing in infants.

Methods

This was a single-center quasi-experimental study conducted from December 2018 to December 2020 at Children’s Hospital New Orleans. A rapid, multiplex polymerase chain reaction bloodstream diagnostic was implemented in January 2019. Antimicrobial Stewardship performed a daily review of all antimicrobials during both periods and made recommendations when necessary. The primary outcome was the difference in time-to-optimal therapy. Secondary outcomes included time-to-effective therapy, 30-day all-cause mortality rate, 30-day recurrent bacteremia rate, and time-to-microbiologic clearance. Patients were excluded if they had an unrelated concomitant infection, withdrawal of care before the result, bacteria not identified by the panel, or were over 6 months of age.

Results

Thirty-five and forty-three patients met inclusion criteria pre-and post-implementation. The median post-natal age was 2 months and median PRISM score was 12 in both groups. Median time-to-optimal therapy was 53.1 hours in the pre-intervention and 24.4 hours in the post-intervention group (-28.7 hours, P = 0.03). Median time-to-effective therapy was 0 and 1.4 hours, respectively (+1.4 hours, P = 0.02). There was no significant difference in 30-day all-cause mortality (3 vs. 4 patients, P = 0.62), 30-day recurrent bacteremia (0 vs. 2 patients, P = 0.2), or microbiologic clearance (37.3 vs. 26.2 hours, P = 0.09).

Conclusion

Implementation of a rapid, multiplex bloodstream diagnostic lead to a significant decrease in time-to-optimal antibiotic therapy in infants when compared to standard microbiological techniques.

Disclosures

All Authors: No reported disclosures
1144. Evaluation of Procalcitnonin Usage in Neonates Presenting with Fever or Suspected Sepsis
Authors: Bhagat Hita , Burns Beech , Lewis James , Yu Diana
Published: December 2021

Background

Clinical evaluation alone is not effective in identifying serious bacterial infections (SBI) in neonates presenting with suspected sepsis and fever. A clinical decision making tool to aide in evaluating neonates presenting to the pediatric emergency department (PED) uses urinalysis, absolute neutrophil count (ANC), and procalcitonin (PCT) and together has high negative predictive value (NPV) for SBI. Use may decrease invasive testing, antibiotic exposure, and rates of admission. The tool was incorporated into hospital guidelines in October 2020. The purpose is to assess implementation and prediction of SBIs.

Methods

This is a single-center quality improvement study at an academic medical center. Neonates less than 60 days presenting with fever or suspected sepsis were included in the baseline group from October 2019- March 2020 or the post-implementation group from October 2020- March 2021. Exclusion criteria were receiving antibiotics 48 hours before PED visit, pre-existing medical conditions, indwelling devices, soft-tissue infections, and ≤ 36 weeks gestation. Implementation and guideline compliance was assessed in neonates aged 29-60 days as the primary outcome. Secondary endpoints include initiation of empiric antibiotics, rates of admission, rates of re-presentation within 30 days, and rates of lumbar punctures in all included patients.

Results

The baseline group had 29 patients and the post-implementation group had 35 patients who met inclusion/exclusion criteria. Baseline characteristics were similar with higher SBI rates in the post-implementation group having 8 SBIs while the baseline group had 4. There were 16 patients aged 29-60 days in the baseline (55%) and 17 in the post-implementation groups (49%). Complete labs were available for 9 patients (53%) and guideline compliance was 89%. NPV in neonates aged 0-60 days with negative urinalysis, ANC, and PCT was 100%. Rates of secondary endpoints were slightly higher in the post-implementation group along with higher rates of infections.

Conclusion

High NPV in this small cohort is an indication for continued use of this tool in neonates presenting to the PED with suspected sepsis or fever. Further education to increase use and expansion to all neonates should be considered based on overall NPV and previous studies.

Disclosures

All Authors: No reported disclosures