bluuebunny/crossref_metadata_2025 huggingface dataset:
1302. Cefiderocol Population Pharmacokinetics and Probability of Target Attainment in Plasma and Epithelial Lining Fluid in Patients with Pneumonia, Bloodstream Infection/Sepsis, or Complicated Urinary Tract Infections
Authors: Katsube Takayuki , Kawaguchi Nao , Echols Roger , Wajima Toshihiro , Nicolau David P
Published: January 2021

Background

Cefiderocol (CFDC) is a novel siderophore cephalosporin with activity against a broad range of Gram-negative bacteria. The aim of this study was to perform population pharmacokinetic (PopPK) analysis and evaluate probability of target attainment (PTA) in plasma and epithelial lining fluid (ELF) based on a modeling and simulation approach.

Methods

PopPK analysis in plasma was conducted using 3427 concentration data from 425 patients with pneumonia, bloodstream infection/sepsis (BSI/sepsis), complicated urinary tract infection (cUTI), or acute uncomplicated pyelonephritis in 3 Phase 2 or 3 studies (NCT03032380, NCT02714595, and NCT02321800), and 91 subjects without any infection in Phase 1 studies. In addition, intrapulmonary modeling was conducted using ELF concentration data from 7 pneumonia patients (NCT03862040) and 20 healthy subjects. Monte-Carlo simulations were performed by generating 1000 virtual patients for each infection site (pneumonia, BSI/sepsis, or cUTI) to predict PTA for 75% of time for which free drug concentration in plasma or ELF (only pneumonia patients) exceeds the minimum inhibitory concentration (MIC; 0.25–16 µg/mL) over dosing interval following CFDC 2 g q8h infused over 3 hours with dose adjustment based on renal function, including augmented renal clearance.

Results

The developed PopPK model described the plasma and ELF CFDC concentrations. Creatinine clearance, body weight, infection site, and albumin concentration were statistically significant covariates on CFDC PK in plasma. There were no clinically significant differences in CFDC plasma exposure based on infection site or with/without ventilation. The penetration ratio of ELF to free plasma in pneumonia patients (0.340) was 1.3-fold higher than that in healthy subjects (0.263). As shown in the table below, plasma PTA was >90% against MICs ≤4 μg/mL, regardless of infection site and renal function. ELF PTA in pneumonia patients was >90% against MICs ≤2 μg/mL and >85% against MICs ≤4 μg/mL, regardless of renal function.

Table. Probability of Target Attainment for 75% fT>MIC or 75% fT>MIC,ELF

Conclusion

The recommended dosing regimen (2 g, q8h, 3-hr infusion) adjusted by renal function provided adequate exposure to CFDC in patients with infections caused by Gram-negative pathogens, irrespective of infection site and renal function.

Disclosures

Takayuki Katsube, PhD, Shionogi & Co., Ltd. (Employee) Nao Kawaguchi, BPharm, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Toshihiro Wajima, PhD, Shionogi & Co., Ltd. (Employee) David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support)
1310. Implementation of AUC:MIC Pharmacy to Dose in an Academic Medical Center: A Pilot Study
Authors: Idusuyi Ann-Marie , Campion Maureen , Belusko Kathleen
Published: January 2021

Background

The new ASHP/IDSA consensus guidelines recommend area under the curve (AUC) monitoring to optimize vancomycin therapy. Little is known about the ability to implement this recommendation in a real-world setting. At UMass Memorial Medical Center (UMMMC), an AUC pharmacy to dose protocol was created to manage infectious diseases (ID) consult patients on vancomycin. The service was piloted by the pharmacy residents and 2 clinical pharmacists. The purpose of this study was to determine if a pharmacy to dose AUC protocol can safely and effectively be implemented.

Methods

A first-order kinetics calculator was built into the electronic medical record and live education was provided to pharmacists. Pharmacists ordered levels, wrote progress notes, and communicated to teams regarding dose adjustments. Patients were included based upon ID consult and need for vancomycin. After a 3-month implementation period, a retrospective chart review was completed. Patients in the pre-implementation group were admitted 3 months prior to AUC pharmacy to dose, had an ID consult and were monitored by trough (TR) levels. The AUC group was monitored with a steady state peak and trough level to calculate AUC. The primary outcome evaluated time to goal AUC vs. time to goal TR. Secondary outcomes included number of dose adjustments made, total daily dose of vancomycin, and incidence of nephrotoxicity.

Results

A total of 64 patients met inclusion criteria, with 37 patients monitored by TR and 27 patients monitored by AUC. Baseline characteristics were similar except for weight in kilograms (TR 80.0 ±25.4 vs AUC 92.0 ±26.7; p=0.049). The average time to goal AUC was 4.13 (±2.08) days, and the average time to goal TR was 4.19 (±2.30) days (p=0.982). More dose adjustments occurred in the TR group compared to the AUC (1 vs 2; p=0.037). There was no difference between the two groups in dosing (TR 15.8 mg/kg vs AUC 16.4 mg/kg; p=0.788). Acute kidney injury occurred in 5 patients in the AUC group and 11 patients in the TR group (p=0.765).

Conclusion

Fewer dose adjustments and less nephrotoxicity was seen utilizing an AUC based protocol. Our small pilot has shown that AUC pharmacy to dose can be safely implemented. Larger studies are needed to evaluate reduction in time to therapeutic goals.

Disclosures

All Authors: No reported disclosures
1314. Neonatal Serum Gentamicin Concentrations following Maternal Once-daily Gentamicin Dosing
Authors: Wilson Genene A , Nelson Allison , Bhagat Palak , Bondi Deborah , Shah Pooja , Kumar Madan
Published: January 2021

Background

Gentamicin is commonly used for peripartum infections. Given literature supporting efficacy of once-daily dosing (ODD) of 5 mg/kg for chorioamnionitis, University of Chicago Medicine made the change from three times daily dosing (TIDD) to ODD. As gentamicin readily cross the placenta, it would be expected that maternal ODD would result in higher gentamicin neonatal serum concentrations following birth.

Methods

This was a single-center, retrospective chart review of all neonates born to mothers receiving peripartum ODD gentamicin within 12 hours of delivery between October 2019 and March 2020. A STAT random gentamicin serum concentration was obtained upon admission in neonates when initiation of antibiotics was desired. Specific dosing recommendations (Table 1) were developed utilizing neonatal population-based pharmacokinetics. The primary outcome was initial neonatal gentamicin serum concentration at birth. Other outcomes were also evaluated. Results were evaluated in two groups based on neonatal serum concentrations of less than 2 mcg/mL (Group 1) versus 2 mcg/mL or greater (Group 2).

Table 1: Neonatal gentamicin dosing algorithm

Results

Thirty-two mother-newborn dyads were included in this study. Baseline demographics are shown in Table 2. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.39 kilograms. The mean initial gentamicin concentration was supratherapeutic at 3.06 + 1.92 mcg/mL among all newborns (Table 3). The mean maternal dose in Group 1 (n=11) was 3.52 mg/kg (3.34, 4.77) based on actual body weight and 4.78 mg/kg (4.34, 5.18) in Group 2 (n=21) (p=0.025). The median time between maternal gentamicin administration and time of delivery varied between the groups at 0.5 hours versus 2.63 hours, respectively (p=0.005). All newborn gentamicin concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n=8) (Figure 1). Overall protocol compliance rate was 81.3%. There were no significant differences in nephrotoxicity or ototoxicity between groups.

Table 2. Baseline Demographics

Table 3. Outcomes

Figure 1. Comparison of maternal gentamicin time from administration to delivery and neonatal serum gentamicin concentrations

Conclusion

This study suggests peripartum ODD of gentamicin may lead to clinically significant serum concentrations in neonates if administered between 1 to 12 hours of birth. Further studies are warranted to evaluate the effects of maternal ODD of gentamicin on newborns.

Disclosures

All Authors: No reported disclosures
1318. Pharmacokinetics and Safety of Cefepime-Taniborbactam (formerly Cefepime/VNRX-5133) in Subjects with Renal Impairment
Authors: Geibel Brooke , Dowell James A , Marbury Thomas C , Smith William , McGovern Paul C , Richards Cynthia , Henkel Tim
Published: January 2021

Background

Taniborbactam is a novel, non-ß-lactam, ß-lactamase inhibitor with activity against serine (Class A, C, D) and metallo (Class B) ß-lactamases including epidemiologically important carbapenemases. Both cefepime and taniborbactam are predominantly renally excreted and are likely to require dose adjustment in patients with renal impairment and end-stage renal disease (ESRD). The current study was designed to evaluate the pharmacokinetics and safety in patients with renal impairment and ESRD.

Methods

This was a Phase 1, open-label study in subjects with normal renal function (eCLCR ≥ 90 mL/min) matched to subjects with mild, moderate, and severe renal impairment (eGFR 60-89, 30-59, and < 30 mL/min/1.73m2, respectively), and patients with ESRD on hemodialysis. Subjects received a single dose of cefepime 2 g and taniborbactam 500 mg; subjects with ESRD received a single dose before HD and after a 9 day washout period, following HD. PK parameters including AUC0-inf and total body clearance (CL) were evaluated. Safety assessments included adverse events (AEs), vital signs, clinical laboratory evaluations, electrocardiograms, and physical examinations.

Results

Thirty-three subjects were enrolled; 67% male, 58% white and 39% black/African Americans. Median age and BMI were 55.0 years and 29.5 kg/m2, respectively. For both cefepime and taniborbactam, exposures increased, and CL decreased with increasing renal impairment (see Table). The hemodialysis extraction ratio was 49.7% and 47.4% for taniborbactam and cefepime respectively. No safety signals were observed and there were no serious adverse events.

Table

Conclusion

Cefepime and taniborbactam CL is similarly reduced with varying degrees of renal impairment. Dialysis removes a high fraction of both drugs. Dose adjustments recommended for cefepime are appropriate for taniborbactam.

Disclosures

Brooke Geibel, BS, Venatorx Pharmaceuticals (Employee, Shareholder) James A. Dowell, PhD, Venatorx Pharmaceuticals (Independent Contractor) Thomas C. Marbury, MD, Venatorx Pharmaceuticals (Independent Contractor) William Smith, MD, Venatorx Pharmaceuticals (Independent Contractor) Paul C. McGovern, MD, Venatorx Pharmaceuticals (Employee) Cynthia Richards, MD, Venatorx Pharmaceuticals (Independent Contractor) Tim Henkel, MD, PhD, Venatorx Pharmaceuticals (Employee, Shareholder)
1321. Population Pharmacokinetic (PK) and Pharmacokinetic/Pharmacodynamic (PK/PD) Target Attainment Analyses for Dalbavancin in Pediatric Patients
Authors: Carrothers Timothy J , Lagraauw H Maxime , Lindbom Lars , Riccobene Todd
Published: January 2021

Background

Dalbavancin is a lipoglycopeptide approved for treating adults with acute bacterial skin and skin structure infections (ABSSSI). It has a terminal half-life of >14 days, which allows for administration as a single-dose regimen. Pediatric studies for dalbavancin include three phase 1 studies and a phase 3 study in patients from birth to 17 years with ABSSSI or neonatal sepsis.

Methods

A population PK model was developed using 1124 concentrations from 211 pediatric patients. Allometric scaling of clearance, and volume parameters was included with exponents fixed at 0.75 and 1, respectively. Based on exploratory analysis and prior knowledge, serum albumin was included as a covariate on all PK parameters, and creatinine clearance or estimated glomerular filtration rate (eGFR) was included as a covariate on clearance. eGFR for patients < 2 years accounted for renal maturation. Additional covariates were assessed by stepwise covariate modeling (SCM). The final model was qualified by visual predictive checks (VPCs) and bootstrapping and was used to simulate 1000 PK profiles for various pediatric age groups, ranging from preterm neonates to adolescents. PK/PD target attainment (PTA) was calculated for targets associated with stasis, 1-log kill, and 2-log kill of Staphylococcus aureus in the murine thigh infection model.

Results

Dalbavancin PK was well-characterized by a 3-compartment model. SCM did not find any significant covariates besides albumin, weight, and renal function. VPCs demonstrated that the final model has good predictive performance across the full age range. Simulations showed that single-dose regimens of 22.5 mg/kg for patients < 6 years and 18 mg/kg for patients 6 to < 18 years resulted in PTA ≥94% for MICs up to 2 mg/L for the stasis target and up to 0.5 mg/L for the 2-log kill target. PTA for pediatric patients was similar to adults, and exposures (AUCs) were contained within the range for adults administered 1500 mg.

Conclusion

Dalbavancin PK in pediatric patients was well-characterized by a 3-compartment model with allometric scaling of clearance and volume and with albumin and renal function included as covariates. Simulations with the final model demonstrate adequate PTA across the entire age range for the regimens used in the phase 3 pediatric study.

Disclosures

Timothy J. Carrothers, ScD, AbbVie (Employee) H. Maxime Lagraauw, PhD, qPharmetra (Employee) Lars Lindbom, PhD, qPharmetra (Employee) Todd Riccobene, PhD, AbbVie (Employee)
1325. Things that go Bump in the Night: Combating Klebsiella pneumoniae co-producing New Delhi metallo-beta-lactamase (NDM) and Mobile Colistin Resistance (MCR)
Authors: Smith Nicholas M , Chen Liang , Boissonneault Katie Rose , Lodise Thomas , Holden Patricia N , Bulitta Juergen B , Bonomo Robert A , Kreiswirth Barry N , Tsuji Brian T
Published: January 2021

Background

The scourge of MBLs among Gram negatives, such New Delhi Metallo-beta-lactamase-producing Klebsiella pneumoniae, has resulted in an overwhelming need for new treatmens. Worryingly, additional acquisition of plasmid-mediated polymyxin resistance through the mcr gene can produce strains resistant to all last line agents. The novel combination of aztreonam (ATM, which is not an MBL substrate) with avibactam (AVI, to inhibit extended spectrum beta-lactamases that inactivate ATM) has been proposed to restore ATM activity.

Methods

K. pneumoniae SZ04 harboring blaNDM-5, blaCTX-M-55, and mcr-1 (MICATM = 128 mg/L, MICPolymyxin B = 4 mg/L, MICAmikacin = 1 mg/L, MICceftazidime/avibactam > 16/4 mg/L) was studied at two initial inoculum (106 and 108 cfu/mL) over 24h in static time kills (SCTK). Concentration arrays of 2-, 3-, and 4-drug combinations of low- and package insert-dose polymyxin B (PMB) ± low- and package insert-dose amikacin (AMI) ± package insert dosing of ATM/AVI were simulated in > 200 individual arms of SCTK. Data were summarized using the Log Ratio Area (LRA) which is calculated by integrating the area under the bacterial killing curve, normalizing to the growth control, then log-transforming. A Hill-type function was fit to the data in order to determine the maximum effect (Emax) and drug concentration for 50% effect (EC50).

Results

When simulating the maximum free concentration of amikacin 15 mg/kg (52 mg/L) in combination with package insert concentrations of ATM/AVI, there was a marked reduction of 3.22 in the LRA compared to the growth control for the 108 cfu/mL starting inocula. Combining ATM with low amikacin (0.813 mg/L) and polymyxin B (0.125 mg/L) resulted in a reduction in LRA of 4.32 at 106 cfu/mL. Model fitting results showed a statistically significant difference in EC50 to amikacin between low and high inocula at 1.24 and 18.1 mg/L, respectively. Combination of AMI with low-concentration PMB (0.125 mg/L) resulted in an increase in the Emax of amikacin to -5.68.

Conclusion

The use of ATM/AVI combinations is a promising option against MBL and MCR co-producing K. pneumoniae. Low-dose strategies of polymyxin or amikacin dosing in combination with ATM/AVI is merits further testing for future translation to the clinical setting to improve efficacy and optimize treatment.

Disclosures

Thomas Lodise, PharmD, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)
1326. Vancomycin Area Under the Concentration-Time Curve (AUC) Estimation Using a Bayesian Approach Versus First-Order Pharmacokinetic Equations: A Pilot Study
Authors: Pearson Jeffrey , Alsowaida Yazed S , Pharm B S , Kubiak David W , Kovacevic Mary P , Dionne Brandon
Published: January 2021

Background

Current guidelines endorse area under the concentration-time curve (AUC)-based monitoring over trough-only monitoring for systemic vancomycin. Vancomycin AUC can be estimated using either Bayesian modeling software or first-order pharmacokinetic (PK) calculations. The objective of this pilot study was to evaluate and compare the efficiency and feasibility of these two approaches for calculating the estimated vancomycin AUC.

Methods

A single-center crossover study was conducted in four medical/surgical units at Brigham and Women’s Hospital over a 3-month time period. All adult patients who received vancomycin were included. Patients were excluded if they were receiving vancomycin for surgical prophylaxis, were on hemodialysis, if vancomycin was being dosed by level, or if vancomycin levels were never drawn. The primary endpoint was the amount of time study team members spent calculating the estimated AUC and determining regimen adjustments with Bayesian modeling compared to first-order PK calculations. Secondary endpoints included the number of vancomycin levels drawn and the percent of those drawn that were usable for AUC calculations.

Results

One hundred twenty-four patients received vancomycin during the study, of whom 47 met inclusion criteria. The most likely reasons for exclusion were receiving vancomycin for surgical prophylaxis (n=40) or never having vancomycin levels drawn (n=32). The median time taken to assess levels in the Bayesian arm was 9.3 minutes [interquartile range (IQR) 7.8-12.4] versus 6.8 minutes (IQR 4.8-8.0) in the 2-level PK arm (p=0.004). However, if Bayesian software is integrated into the electronic health record (EHR), the median time to assess levels was 3.8 minutes (IQR 2.3-6.8, p=0.019). In the Bayesian arm, 30 of 34 vancomycin levels (88.2%) were usable for AUC calculations, compared to 28 of 58 (48.3%) in the 2-level PK arm.

Conclusion

With EHR integration, the use of Bayesian software to calculate the AUC was more efficient than first-order PK calculations. Additionally, vancomycin levels were more likely to be usable in the Bayesian arm, thereby avoiding delays in estimating the vancomycin AUC.

Disclosures

All Authors: No reported disclosures
1327. Vancomycin Dosing by AUC24/MIC in Comparison to Traditional Trough Dosing in Office Infusion Centers (OICs)
Authors: Luu Quyen , Adams John S , Metzger Brian S , Hengel Richard L , Bhattacharyya Rishi , Rhoads David N , Couch Kimberly A , Schroeder Claudia P , Van Anglen Lucinda J
Published: January 2021

Background

New vancomycin (VAN) guidelines have been published, with recommendations that dosing in patients (pts) with methicillin-resistant S. aureus (MRSA) infections be guided by VAN area under the concentration-time curve from 0 to 24 h to MIC ratio (AUC24). The guidelines emphasize daily AUC24 values should be between 400-600 mg*h/L to maximize efficacy and minimize likelihood of acute kidney injury (AKI). Our physicians and clinical pharmacists currently use trough levels to manage outpatient VAN dosing with a general target of 15-20 mg/L. The current pharmacokinetic (PK) model provides an option for dosing using trough or calculated AUC24.

Methods

We identified pts receiving VAN for S. aureus infections (default MIC of 1 mg/mL) from 2018-2020. We conducted a PK evaluation of pts with ≥1 trough level and compared it to model predicted AUC24. Data collected included pt characteristics, VAN regimen, trough concentrations, PK evaluation, and AKI, defined as a 50% decrease in CrCL from baseline. A Bayesian PK model was used to calculate predicted dosing based upon trough concentrations (DoseMeRx®, Moorestown, NJ).

Results

100 pts (mean age: 61±15 yrs, 62% male) from 6 OICs were included, with 82% treated for MRSA and 18% for methicillin-sensitive S. aureus infection. Mean initial dose of VAN in the OIC was 2.6±1 g/d in divided doses, most frequently every 12 hrs (68%). Median duration of outpatient therapy was 28 days [IQR, 16-36]. 69% received VAN in the hospital prior to the OIC. 100 pts had 239 trough levels with a corresponding PK analysis. Mean trough levels were 17.1±6.4 mg/L. Mean corresponding AUC24 was 498±98 mg*h/L. The relationship between trough and AUC24 is shown in Fig 1. 25 evaluations indicated an AUC24 < 400, with 8 (32%) resulting in a dose increase. 13 evaluations indicated AUC24 > 600, with 6 (46%) resulting in a subsequent dose decrease. 4 pts developed reversible AKI, all with AUC24 > 540. Use of AUC24 for dosing provided opportunities to adjust dosing in 38/239 evaluations (16%).

Figure 1. Relationship between Trough and AUC24 (n=239)

Conclusion

This PK evaluation showed a correlation between trough levels and AUC24 with opportunities for VAN dose adjustment using AUC24, and to identify pts at risk for developing AKI. Dosing with AUC24 is particularly useful in the outpatient setting in which true trough evaluations can be difficult to obtain.

Disclosures

Brian S. Metzger, MD, MPH, Allergan (Speaker’s Bureau)Cumberland (Speaker’s Bureau)Melinta (Speaker’s Bureau) Richard L. Hengel, MD, Merck & Co. (Other Financial or Material Support, Grant Steering Committee Member) Kimberly A. Couch, PharmD, MA, FIDSA, FASHP, Allergan (Speaker’s Bureau) Lucinda J. Van Anglen, PharmD, Merck & Co. (Grant/Research Support)
106. Impact and Evaluation of BioFire® FilmArray® Respiratory Panel on Clinical Decision Making and Antibiotic Prescribing
Authors: Manatrey-Lancaster Jenna J , Bushman Amanda , Caliguri Meagan , Espinoza Rossana Rosa
Published: January 2021

Background

The BioFire® FilmArray® respiratory panel (RFA) has been proposed as a tool for timely diagnosis and treatment of respiratory tract infections. However, the impact of the RFA on clinical decision making, most notably antibiotic prescribing, de-escalation and duration has been varied.

Methods

We aimed to determine the impact of RFA results on antibiotic days of therapy (DOT) depending on patient disposition. We conducted a retrospective chart review of adults who had an RFA performed within 48 hours of admission or presentation to the emergency departments (ED) of 3 hospitals in Des Moines, Iowa, between March 3 and March 16, 2019. Patients were excluded if they had a non-respiratory infection with defined indication for antibiotics. RFA results were categorized as influenza, non-influenza virus or negative. Negative binomial regression models were used to calculate rate ratios (RR) for the association between RFA result and DOT.

Results

A total of 486 total patients were included. Patients were divided according to disposition status, with 243 patients admitted and 243 discharged from the ED. Among inpatients, the median DOT was 2 (IQR 0–7). The results of the adjusted analysis for inpatient are shown on Table 1. In this group, RFA result was not associated with DOT (p=0.598 for non-influenza viruses and 0.706 for negative RFA), while having a urine culture done was independently associated with higher rate ratio of DOT (RR 1.85, 95% CI 1.32–2.59; p< 0.001). Among patients discharged from the ED, the median DOT was 0 (0–8). The results of the adjusted analysis for this group are shown on Table 2. Compared to patients with influenza, those with non-influenza viruses had a RR for DOT of 4.18 (95% CI 1.16–14.9; p=0.028) and those with a negative RFA had an RR for DOT of 5.24 (95% CI 1.99–13.8; p= 0.028).

Adjusted analysis for the association between Respiratory Film Array results and Days of Therapy among hospitalized patients

Adjusted analysis for the association between Respiratory Film Array Results and Days of Therapy among patients discharged from the ED

Conclusion

Among inpatients, RFA results did not impact DOT, and in this group, antibiotic use was driven by urine cultures. In contrast, among patients discharged from the ED, a non-influenza virus or a negative RFA was associated with much higher rates of DOT. Our results suggest that different strategies need deployment in the ED compared to inpatient services in order to guide utilization of rapid molecular tests and antibiotic use.

Disclosures

All Authors: No reported disclosures
1330. Development of a Pediatric Emergency Department (ED) Uropathogen Antibiogram and Empiric Urinary Tract Infection (UTI) Treatment Algorithm
Authors: Dass Akshith M , Broadbent Eleanor K , Schanz Caitlin , Louden Nicole , Hansen Lizbeth , Hirsch Elizabeth B , Boeser Kimberly D , Norton Laura E
Published: January 2021

Background

Antimicrobial Stewardship efforts in adult ED settings lead to improved patient outcomes and fewer adverse events. However, there are limited data on incorporation of multiple interventions to assist with empiric and definitive antibiotic therapy selection, particularly in the pediatric ED setting. The purpose of this project was to create an antibiogram and empiric UTI treatment algorithm for use in a pediatric ED.

Methods

This is a multi-phase program implementation in a pediatric ED. Patients aged 2 months -18 years presenting to the ED between January to December 2018 with an ICD10 code for cystitis or pyelonephritis and collection of urine culture were included. Patients were excluded if they were admitted to an inpatient unit or they had a polymicrobial urine culture result. The antibiogram was prepared by including the first isolate of a species from each patient in the given time frame using Clinical and Laboratory Standards Institute recommendations.

Results

A total of 145 unique patients with 160 ED encounters were included in phase I of the project. Median patient age was 5 years (IQR 1.4-8). Discharge diagnosis for 75% of the 160 ED encounters was pyelonephritis. Urogenital flora was cultured from 19.4% of cultures and 21.2% of cultures were without any growth. The most common pathogen isolated was E. coli (39.4%). For ages 2 months – 18 years, susceptibility of urinary E. coli isolates was 95.5% for nitrofurantoin, 92.5% each for ceftriaxone and ciprofloxacin, and 85.1% for cefazolin. Cefdinir and cephalexin were the empiric antibiotics prescribed on discharge 76.3% of the time. After consideration of factors such as antimicrobial stewardship and spectrum of activity, cephalexin was chosen as the treatment of choice for the 2 months – 11 years age group. For children ≥ 12 years, nitrofurantoin was selected as preferred treatment for uncomplicated cystitis while cephalexin was selected as preferred treatment for pyelonephritis.

M Health Fairview University of Minnesota Masonic Childrens ED 2018 E coli isolate antibiogram

Conclusion

An empiric UTI treatment algorithm incorporating local antimicrobial susceptibility pattern alongside recommendations from national organizations was created. Phase II of the project will evaluate the implementation of the algorithm to determine its impact on readmission rates and antibiotic/pathogen mismatch.

Disclosures

Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)
1334. A Qualitative Assessment of Drivers of Antimicrobial Prescribing for Pediatric Patients in Diverse Ambulatory Settings
Authors: Spencer Hillary , Katz Sophie E , Audet Carolyn , Banerjee Ritu , Banerjee Ritu
Published: January 2021

Background

Antimicrobial prescribing rates vary across ambulatory settings and provider types. We sought to identify and compare non-clinical drivers of antimicrobial prescribing for children across diverse outpatient settings.

Methods

We recruited physicians and advanced practice providers (APPs) working in primary care, urgent care (walk-in and pediatric after-hours clinics), and retail health clinics affiliated with Vanderbilt University Medical Center (Table 1). We conducted in-person or telephone interviews using an interview guide created through an iterative process of literature review and sequential pilot testing with residents and administrators from included settings. All interviews were recorded and transcribed verbatim. Analysis is ongoing using inductive methods. The study was IRB approved with a waiver of consent.

Results

Among the 38 providers interviewed to date, 22 (58%) were APPs. Twenty-eight (74%) interviews were conducted by telephone. In a closed-ended question, most providers (82%) identified “guideline recommended” as the primary factor informing their prescribing decisions. Providers perceived that guideline concordant care was determined by a complex interaction of patient, provider, and setting factors (Figure). A major theme identified by providers was that standardized antibiotic prescribing practices within each clinic setting and the larger community was perceived to inform parental expectations. Additionally, shaping parental expectations in a way that aligns with guidelines is a process that happens over time rather than being a one-time event. (Figure, Table 2)

Conclusion

In all outpatient settings, providers caring for children cited clinical guidelines as the most important factor influencing antibiotic prescribing. Providers felt that adherence to guidelines had downstream benefits including standardization of prescribing practices which may shape parental expectations in a way that aligns with guidelines, thus facilitating guideline-concordant care in future encounters. These findings can inform design of outpatient stewardship interventions. Additional provider recruitment and analysis by provider and setting type is ongoing.

Disclosures

Hillary Spencer, MD, MPH, NIH (T32 grant support) (Grant/Research Support)
1338. Analysis of Prescription Guideline Adherence in Pediatric Outpatient Pneumonia Treatment
Authors: Heck Carly , Martin Judith , Kurs-Lasky Marcia
Published: January 2021

Background

Background: Antibiotic resistance is a major public health concern. A modifiable intervention is outpatient antibiotic stewardship. The goal of this study was to review the electronic health records (EHR) of children diagnosed with community acquired pneumonia (CAP) to compare patients who received non-guideline concordant therapy with those prescribed recommended therapy.

Methods

Methods: This was a retrospective chart review of 300 children (6 months to 6 years old) with an outpatient diagnosis of CAP between July 2017 and June 2019. 45 Children’s Hospital of Pittsburgh (CHP) and UPMC Children’s Community Pediatrics (CCP) practices were included. CHP practices are academic-based with trainees involved in visits, while CCP practices do not include trainees. First-line recommended therapy was defined as amoxicillin, second-line therapy as azithromycin or amoxicillin-clavulanate, and all other prescriptions were defined as other. Patients prescribed first-line therapy were compared to patients with second-line therapy or other. If first-line therapy was not prescribed, the EHR was manually reviewed for justification. If drug allergy was listed, the medication allergy and type of reaction were recorded.

Results

Results: In this study the minority of children (43%) were prescribed first-line therapy. This group was younger (57 vs. 63 months of age), more likely to be Non-white (80%), and seen at the CHP locations than those prescribed non-guideline concordant therapy. The average symptom duration was shorter, heart rate and respiratory rate were higher and the presence of fever was more common in the first-line therapy group. Justification for non-guideline therapy was most often reported as to provide coverage for atypical organisms. The most common drug allergy recorded was amoxicillin, and urticaria with unknown timing was the most common type of reaction.

Demographics

Comparison Results

Justification for Second-line / Other Therapy and Drug Allergy Results

Conclusion

This project observed a high proportion of children being prescribed non-guideline concordant therapy for a diagnosis of CAP. Age, race, practice location, and severity of illness measures showed a statistically significant difference between groups. This study highlights the importance of education which reviews the current guidelines and the most likely pathogens for children with CAP.

Disclosures

All Authors: No reported disclosures
1341. Blood Volume Collected for Blood Cultures in Infants with Suspected Neonatal Sepsis in the NICU
Authors: Altez Maria S Rueda , Soghier Lamia , Campos Joseph M , Bost James , Gai Jiaxiang , Hamdy Rana F
Published: January 2021

Background

Blood cultures have high sensitivity to detect bacteremia in septic neonates when >=1 ml of blood is collected. Neonatologists often cite low confidence in microbiologic sampling as rationale for continuing antibiotics without a focus of infection despite negative blood cultures, resulting in prolonged antimicrobial therapy. We aim to describe the blood culture sample volumes in NICU patients, to identify factors associated with sample volumes < 1ml, and to compare the sample volumes of patients treated for culture-negative sepsis with those with bloodstream infections and those treated for a ≤72-hour sepsis rule-out

Methods

Data from this observational cohort study were collected retrospectively and prospectively from NICU patients with blood cultures obtained from September 2018 to February 2019. Clinical data were collected through chart review. All inoculated culture bottles were weighed for volume calculation. We determined the association of age, weight, sample source, and time of collection with volume < 1mL. Continuous variables were analyzed using Wilcoxon-Mann-Whitney, and categorical variables using chi-squared test. For aim 3, the volumes of the groups were compared using analysis of variance.

Results

A total of 310 blood cultures were identified, corresponding to 159 patients. Of these, 49 (16%) were positive. Among the negative blood cultures, 86% were collected in patients who subsequently received antibiotics (Figure 1). Median inoculated volume was 0.6 ml (IQR: 0.1-2.4). Weight and age at time of culture collection, source of sample, and time of collection were not significantly associated with the inoculation of < 1ml of blood. Median volume of blood was 0.6ml (0.3-0.6) for sepsis rule-out, 0.6ml (0.2-0.6) for bloodstream infection, and 0.6ml (0.6-1.4) for culture-negative sepsis. No difference was found among the three groups (p=0.54)

Figure 1. Classification of blood cultures identified during study period

Conclusion

The blood volume collected for cultures in the NICU is lower than recommended. Clinical and environmental characteristics are not significantly associated with the inoculated volume. The volume of blood sampled does not differ in patients with culture-negative sepsis, bloodstream infection and sepsis rule-out, and should not be a justification for longer duration of antibiotic therapy

Disclosures

All Authors: No reported disclosures
1343. Clinical Outcome of Penicillin Skin Testing as an Antimicrobial Stewardship Initiative in the pre-surgical clinic in a community hospital
Authors: rahbani peggy , Monroe-Duprey Laura
Published: January 2021

Background

Penicillin (PCN) allergy is a serious adverse reaction that prevents use of first line therapy. 10% of the population reports a PCN allergy, however less than 1% is truly allergic. Elimination of false allergies significantly impacts patient’s lives and decreases antimicrobial resistance and cost. Penicillin Skin Testing (PST) is a tool to support antimicrobial stewardship (ASP) and to optimize allergy de-labeling. The goal of this pilot study was to implement a pharmacy-nurse driven PST service in the outpatient pre-surgical clinic in a community hospital and to assess the impact of PST on the usage of vancomycin as the pre-op prophylaxis agent.

Methods

In May 2019 a single-center, prospective pilot in the outpatient clinic for pre-surgical adult patients with a documented PCN allergy was approved. Patients were identified via a PCN allergy report, generated from the electronic medical record and interviewed by the ASP pharmacist to identify the type of reaction. The study excluded patients if they were unable to give informed consent, if they took anti-histamines within 72 hours of the test, or if the allergy is clinically insignificant. The nurse administered the test and the ASP pharmacist read the results, documented them in the system, and counseled patients.

Results

A total of 155 patients with PCN allergy qualified for PST and only one patient had a true allergy. 154 patients had a negative test and their allergy was deleted in their electronic health system. In addition, those patients received cefazolin as the antibiotic of choice before their surgery which is narrower spectrum and has less side effects compared to vancomycin. Furthermore, all patients were counseled and acknowledged the impact of the results. After performing PST there was an overall 39% decrease in vancomycin DOT/1000 in the surgical population (2018 May-Dec Average DOT/1000 patient Days=3.75 vs 2019 May-Dec Average DOT/1000 patient Days=2.3. (p < 0.005))

Conclusion

The PST service offers an efficient method to collect a detailed PCN allergy history and de-label patients accordingly. PST helps reduce the pre-surgical prophylaxis use of broad spectrum agents and allergy testing significantly increases patient satisfaction

Disclosures

All Authors: No reported disclosures
108. Impact of Accelerate Pheno System in the Management of Gram-Negative Rod Bacteremia
Authors: Ganapathiraju Iaswarya , Bushman Amanda , Espinoza Rossana Rosa
Published: January 2021

Background

Early pathogen identification and initiation of appropriate antimicrobial therapy is key in the management of Gram-negative rods (GNR) bloodstream infection (BSI). The Accelerate Pheno System (ACC) has been shown to reduce time to GNR identification compared to traditional culture-based methods. We aimed to determine the impact of ACC on the management of GNR BSI in the setting of a well-established antimicrobial stewardship program (ASP).

Table 1

Methods

ACC was introduced in our institution on February 2019. Due to issues incorporating ACC, of patients with GNR BSI, 74% had ACC done and 26% had reporting through traditional methods. This allowed for the design of a retrospective cohort study (instead of a pre-post analysis) to evaluate the association of interest. We included adult patients admitted to three affiliated hospitals in Des Moines, Iowa with BSI due to Enterobacteriales from February 2019 to February 2020. Exclusion criteria were Emergency Department visit only and death within 48 hours of blood culture collection. Primary outcomes were length of hospital stay, days to therapy optimization and in-hospital mortality. Continuous variables were compared by non-parametric methods and categorical variables were compared by Chi-square and Fisher-exact test. Logistic regression models were used to calculate odds ratio for the impact of the intervention on therapy optimization.

Results

A total of 268 patients were analyzed. The median length of stay among patients who had ACC done was 5.2 days (IQR 3.6–8.7) and in those on who ACC was not done it was 5.5 (IQR 3.8–8.9) (p=0.54). No differences in in-hospital mortality were found (p=0.942).

Changes in therapy and missed opportunities for optimization according to whether ACC was done are shown in Table 1. Patients who had ACC done had 99% higher odds of de-escalation within 48 hours of blood culture collection compared to patients who did not have it done (95% CI 1.01–3.92; p=0.044).

Conclusion

In the context of hospitals with baseline short length of stay and a well-established ASP, performing ACC was associated with higher odds of de-escalation within 48 hours of blood culture collection but did not impact length of stay or mortality among patients hospitalized with GNR BSI.

Disclosures

All Authors: No reported disclosures
1350. Optimizing Blood Culture Use in Critically Ill Children: Year One of a Multi-Center Diagnostic Stewardship Collaborative
Authors: Woods-Hill Charlotte Z , Koontz Danielle W , MPH Annie Voskertchian , PhD Anping Xie , Miller Marlene R , MD James C Fackler , PhD Elizabeth A Colantuoni , Milstone Aaron , Milstone Aaron
Published: January 2021

Background

Overuse of blood cultures can lead to false positives and unnecessary antibiotics. Our objective was to describe the implementation and 12-month impact of a multi-site quality improvement collaborative to reduce unnecessary blood cultures in pediatric intensive care unit (PICU) patients.

Methods

In 2018, 14 PICUs joined the Blood Culture Improvement Guidelines and Diagnostic Stewardship for Antibiotic Reduction in Critically Ill Children (Bright STAR) Collaborative, designed to understand and improve blood culture practices in PICUs. Guided by a multidisciplinary study team, sites 1) reviewed existing evidence for safe blood culture reduction, 2) assessed local practices and barriers to change, and 3) developed and implemented new blood culture practices informed by local context. We facilitated and monitored project progress through phone calls, site visits, and collaborative-wide teleconferences. We collected monthly blood culture rates and monitored for delays in culture collection as a safety balancing metric. We compared 24 months of baseline data to post-implementation data (2-14 months) using a Poisson regression model accounting for the site-specific patient days and correlation of culture use within a site over time.

Results

Across 14 sites, there were 41,986 pre-implementation blood cultures collected over 238,182 PICU patient days. The mean pre-implementation site-specific blood culture rate was 19.42 cultures/100 patient days (range 9.59 to 48.18 cultures/100 patient days). Post-implementation, there were 12,909 blood cultures collected over 118,600 PICU patient days. The mean post-implementation rate was 14.02 cultures/100 patient days (range 5.40 to 37.57 cultures/100 patient days), a 23% decrease (relative rate 0.77, 95% CI: 0.60, 0.99, p = 0.04). In 12 months post-implementation, sites reviewed 463 positive blood cultures, and identified only one suspected delay in culture collection possibly attributable to the site’s culture reduction program.

Bright STAR Collaborative Site Blood Culture Rate 100 Patient Days

Conclusion

Multidisciplinary teams facilitated a 23% average reduction in blood culture use in 14 PICUs. Future work will determine the impact of blood culture diagnostic stewardship on antibiotic use and other important patient safety outcomes.

Disclosures

James C. Fackler MD, MD, Rubicon Health LLC (Other Financial or Material Support, Founder)
1352. Pediatric azithromycin prescriptions in a healthcare system from 2016-2018
Authors: Petrone Skylar , Garavaglia Lisa , Gupta Shipra
Published: January 2021

Background

In 2017, the Centers for Disease Control and Prevention (CDC) estimated that 30% of all antibiotics prescribed in outpatient clinics are unnecessary, with children receiving more antibiotics than any other age group. Among those antibiotics being prescribed, azithromycin is one of the most commonly prescribed antibiotics.

Methods

We reviewed antimicrobial prescribing data of children 0 to 19 years of age who visited West Virginia University (WVU) Health system which is the flagship institution for the state. We reviewed information of patients who were prescribed azithromycin by healthcare providers between January 2016 and December 2018. We included prescribing data from urgent care centers, outpatient clinics and emergency departments. The primary visit diagnosis associated with the visit was reviewed.

Results

During the study period there were 29,983 visits identified during which antibiotics were prescribed and azithromycin was prescribed in 40.6% of those visits. The majority of visits occurred between the months of October through February (54.4%), with December having the most visits. There were 11,934 unique patients identified and only 26.5% of these patients were marked as allergic to penicillin (PCN) or amoxicillin. The distribution of the age groups for azithromycin prescriptions is shown in figure 1. The age group of 11-19 years had the highest azithromycin prescription rate (38.7%) and the most common diagnosis for this group was pharyngitis. The distribution of the common diagnoses associated with azithromycin prescriptions can be seen in figure 2 and acute otitis media (AOM) was the most common diagnosis (23.6%).

Figure 1- Age distribution of children who received azithromycin prescriptions during the study period

Figure 2- Distribution of diagnoses associated with azithromycin prescriptions

Conclusion

Acute otitis media and pharyngitis accounted for almost half of the diagnoses associated with azithromycin prescriptions. Treatment guidelines for both conditions recommend PCN-based therapy as first-line treatment unless there is a history of PCN allergy. Only a quarter of the patients had allergy documented to PCN or amoxicillin and, therefore, azithromycin would be considered a suboptimal antimicrobial choice. These results provide us with a stewardship opportunity to nudge providers to select appropriate antimicrobial based on diagnosis and history of allergy.

Disclosures

All Authors: No reported disclosures