bluuebunny/crossref_metadata_2025 huggingface dataset:
1328. Vancomycin exposure and utilization following implementation of an AUC-guided monitoring guideline in children
Authors: Quraishi Ruquaya , Ashouri Negar , Beuttler Richard , Tran Martin T
Published: January 2021

Background

The 2009 guideline for vancomycin (VAN) monitoring recommended trough (TR) of 15-20 mg/L to correlate with AUC/MIC ≥ 400. Studies have suggested attainment of target AUC/MIC ratio with TR 7-11 mg/L in most children. Prior to 2018, TR 15-20 mg/L was the primary target for VAN therapeutic monitoring at CHOC Children’s. Beginning in 2018, a clinical guideline was implemented which recommend targeting AUC/MIC of 400-600 or TR of 7-15 mg/L. Our objectives are to evaluate differences in VAN utilization, exposure, nephrotoxicity and cost savings between pre (Pre-guideline, pG) and post implementation (Post-guideline, PG) of a VAN monitoring guideline at CHOC Children’s.

Methods

Retrospective chart review of patients prescribed VAN between Jan 2016 – Jun 2017 (pG) and Jan 2018 – Jun 2019 (PG). Primary objectives evaluated differences in pharmacokinetic (PK), AUC and rate of nephrotoxicity in patients 3 months to < 18 years who received VAN ≥ 24 hour with ≥ 1 TR. Secondary objectives assessed differences in overall VAN utilization following guideline implementation.

Results

Seventy patients were included in the PK analysis, 35 in pG and 35 in the PG group. Median age, weight, gender, baseline creatinine, concurrent nephrotoxic agents were similar. There were no differences in duration of therapy or starting doses (mg/kg/day) between the two groups. The highest daily dose (mg/kg) and AUC (mg*h/L) attained was significantly higher in pG compared to PG group (74.9 vs. 59.9, p = 0.002 and 647 vs. 469, p < 0.0001), respectively. Changes in AUC from the initial regimen to the highest adjusted regimen was also higher in pG group (532 vs. 647, p = 0.0008) while there was no difference in PG group (459 vs. 469, p = 0.647). More patients experienced nephrotoxicity in pG compared to PG (11.4% (4/35) vs. 0 (0/35), p = 0.039). Logistic regression analysis identified AUC 800-900 as a significant risk for nephrotoxicity. Compared to pG, PG resulted in a net reduction in VAN utilization of 19.7 DOT per 1000 patient days, savings of $100,150 and 738 fewer levels drawn.

Conclusion

In line with the 2020 consensus guideline recommendation for AUC-based VAN monitoring, our study found AUC-guided VAN monitoring in children resulted in less exposure, utilization, and nephrotoxicity.

Disclosures

All Authors: No reported disclosures
1329. Vancomycin Therapeutic Drug Monitoring: How to hit the Curve
Authors: Vala Michael , Chapin Ryan , Mercuro Nicholas J , McCoy Christopher
Published: January 2021

Background

For the management of serious S. aureus infections, area-under-the curve to minimum inhibitory concentration (AUC/MIC) applied dosing is recommended as the preferred method to goal trough-based monitoring. This pharmacodynamic dosing demonstrates efficacy with optimized exposure and decreased nephrotoxicity. While two levels are ideal for estimating AUC/MIC mathematically, the logistics and costs may outweigh the benefits of this approach. This study will compare AUC/MIC estimates using two single-level pharmacokinetic calculators (C2 and C3) and a Bayesian dosing calculator (C1) versus steady-state troughs.

Methods

A retrospective cohort study using a data repository to identify patients from 2019 included patients on intravenous vancomycin for greater than 48 hours with a steady state trough. Patients on dialysis or with unstable renal function were excluded. Vancomycin AUC/MIC and peak levels were estimated using C1, C2, and C3. The objective was to assess correlation of trough levels of 10-20mcg/ml to an AUC/MIC of 400-600 mg∙h/L. Secondary outcomes included examining the difference in R-squared values of the three calculators, and the percentage of patients with dose adjustments.

Results

55 patients met inclusion criteria. Of 55 troughs, 78% were 10-20mcg/ml and 5% were >20mcg/ml. On average, the three calculators found 85% of all initial troughs and 93% of therapeutic troughs correlated to an AUC >400. However, less than half of therapeutic troughs corresponded to an AUC of 400-600 mg∙h/L. Nearly 70% of patients had one or more dose adjustments often for unclear reasons as the AUC/MIC target of 400-600 mg∙h/L was met in 29-63% of initial adjustments. The three different calculators showed noticeable variability in calculating AUC/MIC.

Figure 1

Figure 2

Figure 3

Conclusion

A weak relationship between AUC/MIC and steady state troughs was found. Excess vancomycin exposure was demonstrated in 39% of therapeutic troughs. Over 25% of dose adjustments were deemed unnecessary. Utilizing AUC/MIC estimates for vancomycin may limit excess exposure while reducing the overall number of drug levels. Selecting a single-level calculator is problematic with the high degree of variation between calculators.

Figure 4

Disclosures

All Authors: No reported disclosures
1331. Reducing Inpatient Antimicrobial Treatment Duration for Febrile Infants through Implementation of Rapid Diagnostic Testing and Clinical Risk Definition
Authors: Erdem Guliz , Watson Joshua , Buckingham Don , Ramilo Octavio , Barson William J
Published: January 2021

Background

The management approach to febrile infants remain challenging. Despite new advances in rapid diagnostic testing, febrile infants with a viral infection could receive prolonged antimicrobial treatment due to concerns for co-existing serious bacterial infection (SBI). We sought to decrease the duration of antibiotic treatment in febrile infants less than 8 weeks of age hospitalized on inpatient infectious disease service following sepsis evaluation, who have enterovirus, parechovirus, or respiratory viruses detected, from average 30 hours to 24 hours and sustain for six months.

Figure 1. Antibiotic Treatment Duration of Infants Underfoing Evaluation for Sepsis

Figure 2. Length of Stay in Infants Underfoing Sepsis Evaluation

Methods

A new management guideline that defined “low-risk” infants, as well as inclusion and exclusion criteria, was created to monitor the accurate duration of parenteral treatment and length of hospitalization. Respiratory viruses were detected by a multiplex PCR assay. We created a QlikSense App for further clinical characterization of patients and follow-up. This management guideline was adapted as a quality improvement division initiative. Control charts were used to assess the impact of the interventions.

Figure 3. Readmissions in Infants Underfoing Sepsis Evaluation

Results

The management guideline was developed and implemented by pediatric infectious disease faculty. Febrile infants < 8 weeks of age were included if they had both documented viral infections and sepsis evaluation. 178 infants were admitted with fevers in 2018 and 148 infants were admitted in 2019. The mean inpatient antibiotic treatment duration decreased from 27.7 hours in 2018 to 24.9 hours in 2019 (P > 0.05) (Figure 1). There was no significant difference in length of hospitalization or 30-day readmission rates (Figure 2 and 3). There was no reported readmission for SBI.

Conclusion

Antibiotic treatment could be discontinued in clinically stable infants with a documented viral infection after 24 hours of negative blood, CSF, and urine bacterial culture incubation so as not to receive unnecessary prolonged inpatient treatment that may increase side effects. In addition to possible decreased treatment side effects our protocol led to decreased patient care costs with no documented changes in readmission rates.

Disclosures

Octavio Ramilo, MD, Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Medimmune (Grant/Research Support)Merck (Advisor or Review Panel member)NIH/NIAID (Grant/Research Support)Pfizer (Consultant, Advisor or Review Panel member)Sanofi/Medimmune (Consultant, Advisor or Review Panel member)
1332. Single Dose Oral Amoxicillin Challenge is a Safe and Effective Strategy to Delabel Penicillin Allergies among Low Risk Hospitalized Children
Authors: Searns Justin B , Stein Amy , MacBrayne Christine , Sarin Tara , Lin Taylor , Duffey Hannah , Hicks Allison , Wickstrom Kaylee , Bajaj Lalit , Bauer Maureen , Carel Kirstin
Published: January 2021

Background

Over 90% of children with reported penicillin allergy can tolerate penicillin without incident. Developing effective and safe strategies to remove inappropriate penicillin allergies has the potential to improve care; however, guidance on how to identify, test, and delabel patients is limited.

Methods

In April 2019, Children’s Hospital Colorado (CHCO) implemented a penicillin allergy clinical pathway (CP) alongside a risk assessment tool to stratify patients based on allergic history (Figure 1). Patients at “no increased risk” were educated and delabeled without testing. Low risk patients were offered an oral amoxicillin drug challenge with close observation. A single, non-graded, treatment dose of amoxicillin (45 mg/kg, max dose 1000mg) was used for low risk patients, and no preceding allergic skin testing was performed. Patients with no signs or symptoms of allergic response 60 minutes after amoxicillin administration were delabeled. Children delabeled of penicillin allergies on the CHCO hospital medicine service were compared between the pre-CP (1/1/17-3/31/19) and post-CP (4/1/19-3/31/20) cohorts.

Figure 1. Penicillin Allergy Risk Assessment

Results

Pre-CP, 683/10624 (6.4%) patients reported a penicillin allergy and 18/683 (2.6%) were delabeled by discharge. Post-CP, 345/6559 (5.3%) patients reported a penicillin allergy and 47/345 (13.6%) were delabeled by discharge (P-value < 0.0001, Figure 2). Among the 47 post-CP patients, 11 were delabeled by history alone, 19 underwent oral amoxicillin drug challenge per CP, and 17 received a different treatment dose penicillin per treatment team. Only one penicillin-exposed patients had a reaction. This patient developed a delayed, non-progressive rash and had penicillin allergy restored to their chart. No patient required emergency medical intervention, and none were “relabeled” penicillin allergic in the 6 months following discharge.

Figure 2. Monthly Rate of Penicillin Allergic Patients Delabeled by Discharge

Conclusion

A drug challenge using a single non-graded dose of oral amoxicillin is a safe and effective strategy to delabel low risk children of inappropriate penicillin allergies when implemented alongside a risk assessment tool. Further studies are needed to evaluate the long-term benefits of delabeling inappropriate penicillin allergies and to continue monitoring for adverse events.

Disclosures

All Authors: No reported disclosures
1333. A Cross-Sectional Analysis of Inappropriate Outpatient Antibiotic Use in Children Insured by Kentucky Medicaid
Authors: Wattles Bethany A , Jawad Kahir S , Feygin Yana , Kong Maiying , Vidwan Navjyot , Stevenson Michelle D , Smith Michael J
Published: January 2021

Background

Kentucky (KY) consistently has one of the highest rates of outpatient pediatric antibiotic prescribing in the nation. Previous analyses identified significant variation in volume of antibiotic prescribing by geographic location, patient demographics, and provider type, but less is known about the appropriateness of this prescribing. We describe appropriateness of outpatient antibiotic prescribing in children insured by KY Medicaid.

Methods

We utilized KY Medicaid pharmacy and medical claims from 2017 for children < 20 years. Patient demographic variables were abstracted from Medicaid enrollment data. Antibiotic prescriptions were identified by NDC and matched to medical claims within 3 days prior to fill date to identify corresponding diagnoses via ICD-10 codes. A previously published appropriateness classification scheme (Chua, BMJ 2019) was applied to categorize antibiotic prescriptions as “appropriate”, “potentially appropriate”, “inappropriate” or “not associated with indication”.

Results

Of the 779,751 antibiotic prescriptions included, 19.5% were appropriate, 45.3% were potentially appropriate, 20.8% were inappropriate, and 14.4% were not associated with an indication (Table 1). Inappropriate prescriptions were more common among children 0-2 years (24.4%) and those living in non-metro areas (22.2%). Antibiotics prescribed by general practitioners were also more likely to be inappropriate (22.2%). The most common diagnoses for each category are summarized in Table 2. Amoxicillin was the most commonly prescribed antibiotic in all categories. Azithromycin was more frequently prescribed for inappropriate indications or those not associated with a diagnosis code. Cefdinir was more common for appropriate and potentially appropriate indications.

Table 1: Antibiotic Prescription Characteristics, 2017

Table 2: Top Diagnoses for Antibiotic Prescriptions by Category

Conclusion

Inappropriate antibiotic prescribing is more common among young children living in non-metro areas seen by general practitioners. Outpatient antibiotic stewardship interventions should target these patient demographics and provider types. This classification scheme to describe inappropriate prescribing is feasible for use in pediatric Medicaid patients and could serve as a valuable metric for provider feedback reports on antibiotic use.

Disclosures

Bethany A. Wattles, PharmD, Kentucky Medicaid (Grant/Research Support)Merck (Grant/Research Support) Michael J. Smith, MD, MSC.E, Kentucky Medicaid (Grant/Research Support)Merck (Grant/Research Support)
1336. Alcohol Impregnated Caps and Ambulatory CLABSI: Multicenter Cluster Randomized, Crossover Trial
Authors: Milstone Aaron , Milstone Aaron , Rosenberg Carol E , Yenokyan Gayane , Koontz Danielle W , Miller Marlene R
Published: January 2021

Background

Central line-associated bloodstream infections (CLABSI) cause significant morbidity and mortality and occur more commonly in the ambulatory setting in pediatric oncology patients. Whether alcohol impregnated caps placed on central venous lines can prevent CLABSI in ambulatory pediatric oncology patients is unknown.

Methods

We performed a cluster-randomized, 2 period, crossover trial at 16 pediatric hematology/oncology clinics. Clinics were randomly assigned to usual ambulatory central line care per each institution (control) compared to use of 70% isopropyl alcohol-containing caps at home (intervention). Caps were only used in the ambulatory setting. The primary outcome was ambulatory CLABSI. Secondary outcomes included ambulatory mucosal barrier injury (MBI) CLABSI, secondary blood stream infections, single positive blood cultures, and positive blood cultures.

Results

Of the 16 participating clinics, 15 clinics completed both assignment periods. As assigned, there was no statistically significant reduction in incidence of ambulatory CLABSI in patients using 70% isopropyl

alcohol-impregnated caps at home (1.23 per 1000 days, 95% CI 0.94, 1.60) compared with standard practices (1.38 per 1000 days, 95% CI 1.08, 1.77; adjusted incidence rate ratio [aIRR] 0.83, 95% CI 0.61,

1.12). There was no reduction in incidence of ambulatory MBI-CLABSI (aIRR 0.57, 95% CI 0.23, 1.40), single positive blood culture (aIRR 1.35, 95% CI 0.74, 2.48), or positive blood cultures (aIRR 0.80, 95% CI 0.60, 1.07). In the per protocol analysis, there was a reduction in incidence of positive blood cultures in ambulatory patients using 70% isopropyl alcohol-impregnated caps at home (1.51 per 1000 days, 95% CI

1.14, 2.00) compared with standard practices (1.88 per 1000 days, 1.47, 2.39; aIRR 0.72, 95% CI 0.51, 1.00).

Conclusion

Isopropyl alcohol- impregnated caps did not lead to a statistically significant reduction in CLABSI rates in ambulatory hematology/oncology patients, however, there was a reduction in positive blood cultures in the ambulatory setting in the per protocol analysis. Further research is needed to understand the clinical impact of alcohol-impregnated caps in the ambulatory setting.

Disclosures

All Authors: No reported disclosures
1337. An Outpatient Antimicrobial Stewardship Initiative for Urinary Tract Infections in Primary Care Pediatrics
Authors: Mannix Mary Kathryn , Islam Shamim
Published: January 2021

Background

Studies have showed that 30% of antibiotics prescribed in the outpatient setting are unnecessary. Acute UTI constitutes a significant health burden in outpatient pediatrics affecting ~2.8% of children every year. Antibiotics are often started empirically when diagnosing UTI making pediatric UTIs an ideal target for outpatient stewardship. The primary objective was to reduce the use of broad-spectrum empiric antibiotics with a secondary objective to study antibiotic discontinuation in culture negative cases.

Methods

The electronic medical records of two pediatric practices were screened for patients aged 2 months to 18 years diagnosed with uncomplicated UTI using ICD-10 codes N39, R30 and R35. The definition of a positive urine culture was > 50,000 CFU/ml if catheterized and > 100,000 CFU/ml if clean-catch specimen. A two-year pre-intervention period began in January 2018. An audit and review of urine culture processes were studied at each site with a subsequent educational intervention, a direct, one-hour session focused on the use of cephalexin as first-line empiric therapy based on the local antibiogram. The post-intervention period began at each site after the intervention. A COVID-19 sub-analysis was performed for the post-intervention period.

Results

During the study, 515 encounters and 113 encounters were included during the pre- and post-intervention periods, respectively. 74.4% (383/515) of pre-intervention encounters had empirically prescribed antibiotics; higher-generation cephalosporins (i.e. cefdinir, cefprozil) most frequently. Antibiotics were empirically prescribed in 75.2% (85/113) of post-intervention encounters with a statistically significant increase in cephalexin use (32/85, 37.6%, p < 0.01) and reduction in higher-generation cephalosporin use (p < 0.01), Figure 1. In the COVID-19 analysis, empiric antibiotic prescribing trended towards baseline as providers were relying largely on telemedicine, Figure 2.

Figure 1: Empiric Antibiotic Prescribing Pre- and Post-InterventionF

Figure 2: Empiric Antibiotic Prescribing - %

Table 1: Pre- and Post-Intervention

Conclusion

The educational intervention was effective in changing antibiotic prescribing with an increased use of narrow spectrum antibiotics. This change waned without reinforcement and reliance on telemedicine during COVID-19. Antibiotic discontinuation in culture-negative cases remains an important area for improvement.

Disclosures

All Authors: No reported disclosures
107. Impact of a Rapid Blood Culture Identification Panel at a Community Teaching Hospital: a Pre-Post Quasi-Experiment
Authors: Trinh Catherine , Richardson Steven , Ereshefsky Benjamin
Published: January 2021

Background

Rapid diagnostic tests (RDT) for positive blood cultures can lead to quicker identification of organisms and key resistance elements. As a result time to targeted therapy may decrease, thus reducing the duration of broad, empiric antibiotic use. The purpose of this study was to determine the impact of implementing the BioFire® FilmArray® Blood Culture Identification (BCID) Panel for gram-positive organisms on antimicrobial process measures and patient outcomes at an academic community hospital.

Methods

This was a single-center, pre-post intervention, quasi-experimental study evaluating hospitalized adult patients who had at least one positive blood culture with gram-positive organisms from June 1, 2018 to August 31, 2018 and June 1, 2019 to August 31, 2019. Patients in the pre-intervention group were randomized and post-intervention patients were matched by identified organism. The primary outcome was the time to targeted therapy from blood culture collection. Secondary outcomes included time to targeted therapy from positive Gram stain, vancomycin and anti-pseudomonal β-lactam length of therapy (LOT), institutional vancomycin days of therapy (DOT), length of stay (LOS), and estimated hospitalization costs.

Results

A total of 75 patients in each group were included. The time to targeted therapy from blood culture collection was significantly decreased after RDT implementation [32.9 (23.2–51.8) hours vs. 49.2 (37.1–76.3 hours, p < 0.001)], as was time to targeted therapy from Gram stain results [8.5 (0–25.2) hours vs. 30 (19.4–52.9) hours, p < 0.001]. No difference was found between the groups with respect to LOS or estimated hospitalization cost. Overall the vancomycin LOT [0.86 (0.09–2.38) days vs. 2.18 (1.37–4.34) days, p = 0.001] and anti-pseudomonal β-lactam LOT for MRSA, MSSA, Streptococcus, and Enterococcus subgroup [1.15 (0.06–2.07) vs. 1.78 (1.28–2.89) days, p = 0.026] were significantly decreased in the post-RDT group.

Figure 1: Institutional Use of Vnacomycin

Conclusion

Implementation of a rapid diagnostic test on gram-positive blood cultures was associated with decreased time to targeted therapy from blood culture collection, time to targeted therapy from positive culture, and vancomycin LOT.

Disclosures

All Authors: No reported disclosures
1339. Antibiotic Prescribing Varies among Patients with a Documented Penicillin or Cephalosporin Adverse Drug Reaction
Authors: Lee Brian R , Newland Jason , Goldman Jennifer
Published: January 2021

Background

Studies have shown that over half of hospitalized children receive an antibiotic during their encounter, of which between 30-50% is considered inappropriate. Antibiotic prescribing is further complicated as approximately 10% of children are labeled beta-lactam allergic, resulting in the use of either broad-spectrum or suboptimal therapy. The purpose of this study was to compare antibiotic prescribing between patients with a documented ADR vs. those without using a nationwide sample of hospitalized children.

Methods

We performed a point prevalence study among 32 hospitals between July 2016-December 2017 where data were collected via chart review on pediatric patient and antimicrobial characteristics, including the indication for all antimicrobials. In additional, ADR history data were collected on which antimicrobial(s) were documented (e.g., penicillin, cephalosporins). Patients were mutually assigned into either: 1) no documented ADR; 2) penicillin ADR-only; 3) cephalosporin ADR-only; and 4) ADR for both penicillin and cephalosporin. The distribution of antibiotics were compared between the ADR groups, stratified by the indication for treatment.

Results

A total of 12,250 pediatric patients (17,929 antibiotic orders) who were actively receiving antibiotics were identified. A history of penicillin and cephalosporin ADR was documented in 5.5% and 2.8% of these patients, respectively. When compared to patients with no documented ADR, penicillin ADR patients were more likely to receive a fluoroquinolone for a SSTI infection (odds ratio [OR]: 5.6), surgical prophylaxis (OR: 18.8) or for surgical treatment (OR: 5.2) (see Figure). Conversely, penicillin ADR patients were less likely to receive first-line agents, such as narrow-spectrum penicillin for bacterial LRTI (OR: 0.08) and piperacillin/tazobactam for GI infections (OR: 0.22). Cephalosporin ADR patients exhibited similar patterns with increased use of carbapenems and fluoroquinolones when compared to patients with no ADR.

Figure 1: Odds of Receiving Select Antimicrobials Among PCN ADR Patients When Compared to Non-ADR patients, by Indication

Conclusion

A large, nationwide sample of pediatric patients who were actively prescribed antibiotics helped identify several diagnoses where comprehensive guidelines for appropriate ADR prescribing and increased ADR de-labeling initiatives are needed to ensure optimal treatment.

Disclosures

Brian R. Lee, MPH, PhD, Merck (Grant/Research Support) Jason Newland, MD, MEd, FPIDS, Merck (Grant/Research Support)Pfizer (Other Financial or Material Support, Industry funded clinical trial)
1340. Assessment of the impact of multiplex PCR panels in sepsis evaluations of young febrile infants
Authors: Ratliff Hunter , Tran Tuan , Williams-Bouyer Natalie , Nguyen Diana
Published: January 2021

Background

The management of febrile infants under the age of 3 months has long been a controversial topic, often requiring them to be subject to a battery of tests, antibiotics, and hospitalization. Multiplex polymerase chain reaction (PCR) panels can provide a rapid diagnosis, but their role in managing these patients is still unknown.

Our objective was to determine if multiplex respiratory and meningitis/encephalitis PCR panels decreased antibiotic duration of therapy (DOT) and hospital length of stay (LOS) when used in sepsis evaluations of febrile infants less than 90 days of age.

Methods

We performed a retrospective chart review of infants younger than 90 days old who were admitted to the pediatric ward for concerns of fever or sepsis from 1/1/2016 to 9/30/2019. Subjects with documented bacterial infections were excluded. Our primary outcomes were differences in DOT and LOS between patients admitted before and after PCR panels became available (Pre-PCR era and PCR era).

Results

118 subjects were included in our analysis, with 52 (44.1%) coming from the Pre-PCR group. Descriptive statistics, stratified by era, are available in Table 1. The unadjusted mean LOS and DOT decreased by 8.4 (P = .003) and 32.8 (P < .001) hours, respectively.

Multivariate regression demonstrated that LOS was 1.16 times longer in the Pre-PCR era (95% CI: 1.10 - 1.22; P < .001). Similarly, patients in the Pre-PCR era had DOT that was 1.95 times longer (95% CI: 1.55 - 2.46; P < .001) when adjusting for covariates.

Adjusted LOS and DOT by Era and Diagnosis

PCR panel results by pathogen

Conclusion

We conclude that multiplex PCR panels can potentially influence the management of young febrile infants admitted for sepsis evaluations by rapidly diagnosing viral infections and thus decreasing DOT and LOS. In turn, that may improve patient outcomes and satisfaction, as well as possibly decrease costs. Multiplex PCR panels should be considered as part of routine sepsis evaluations in young febrile infants. Larger studies are needed, including in depth cost analysis.

Table 1: Demographics

Table 2: Results between Eras

Disclosures

All Authors: No reported disclosures
1342. Clinical failure rates of amoxicillin for the treatment of acute otitis media in young children
Authors: Frost Holly M , Dominguez Samuel , Parker Sarah , Byars Andrew , Michelson Sara , Keith Amy , Jenkins Timothy C
Published: January 2021

Background

Acute otitis media(AOM) is the most common indication for antibiotics in children. The primary pathogens that cause AOM have changed since the introduction of the pneumococcal conjugate vaccine(PCV). The clinical failure rate of amoxicillin for treatment of AOM post-PCV is unknown.We aimed to determine the clinical failure rate of amoxicillin for the treatment of uncomplicated AOM in children.

Organisms identified on culture and amoxicillin treatment failure from nasopharyngeal specimens of children age 6-35 months with uncomplicated acute otitis media at Denver Health, Denver, CO from April 2019-March 2020.

Methods

Children age 6-35 months seen at Denver Health, Denver, CO with uncomplicated AOM and prescribed amoxicillin were prospectively enrolled. An interim analysis of patients enrolled from April 2019-March 2020 was completed. Patients completed surveys that included the AOM-SOS©(UPMC, Pittsburgh, PA) at enrollment, days 5, 14, and 30 and had chart abstraction completed. Treatment failure was defined as: (1) requiring a new antibiotic within 14 days; (2) AOM-SOS© score on day 5 or 14 not improved by a relative reduction of ≥ 55% from baseline. Recurrence was defined as requiring a new antibiotic within 15-30 days. Nasopharyngeal swabs were obtained and bacterial culture was completed.

Results

In total,110 patients were enrolled. Rates of treatment failure defined by AOM-SOS© were 28.4%(37; 95%CI:25.5-33.6%) at 5 days and 15.5%(27; 95%CI:17.5-24.5%) at 14 days. However, only 4.5%(5; 95%CI:2.0-4.5%) required a new antibiotic. Recurrence occurred in 5.5% (6, 95%CI:2.5-5.5%) of patients. Of patients who had not received antibiotics before enrollment(82), culture yielded no organism in 17.0%, one organism in 42.7%, and multiple organisms in 40.0% (Table). M.catarrhalis was the most frequently identified organism (53.7% of children). Of H.influenzae isolates 52.9% (9/17) produced beta-lactamase, resulting in no treatment failures or recurrences requiring a new antibiotic. Failure rates were similar between organisms.

Conclusion

Despite the change in otopathogen prevalence post-PCV, preliminary data suggest that while early subjective treatment failure was common, the 14 day treatment failure and 30 day recurrence rates was low when measured by need for a new antibiotic. Failure was low even among patients with organisms that would not be expected to be treated successfully with amoxicillin, such as those with beta-lactamase producing H.influenzae and M.catarrhalis.

Disclosures

Samuel Dominguez, MD, PhD, BioFire (Consultant, Research Grant or Support)
1344. Impact of Pharmacist-Physician Team on Antimicrobial Utilization at a Pediatric Hospital
Authors: Sapozhnikov Julia , Fernandez Marisol
Published: January 2021

Background

“Handshake stewardship” is now considered a leading practice in antimicrobial stewardship (AMS) by The Joint Commission. This study aims to evaluate the impact of a pharmacist-led and physician-pharmacist led handshake stewardship method on antimicrobial utilization at a pediatric hospital.

Methods

This was a single-center, retrospective quality improvement study at a teaching children’s hospital in central Texas. We retrospectively measured hospital-wide antimicrobial utilization from June 2015 to May 2020. We compared the time periods with an ID pharmacist participating in handshake stewardship ([A] July 2012 to April 2015,[B] May 2015 to May 2018 and [D] August 2019 to May 2020) and without an ID pharmacist ([C] June 2018 to July 2019). We also compared time periods with only an ID pharmacist led ASP [A] compared to a physician-pharmacist led ASP [B].The primary endpoint was days of therapy per 1,000 patient days (DOT/1000 PD).

Table 1. Overall Antimicrobial Utilization During Changes in ASP Structure

Results

Antimicrobial utilization during pharmacist-led ASP [A] was significantly higher than during the pharmacist-physician led ASP time period [B] (95% CI, 68.8-76.8; P=0.001). No significant difference was observed for mean hospital-wide antimicrobial, meropenem, piperacillin-tazobactam, or cefepime DOT/1000 PD from period [B] to [C]. However, the increase in mean DOT/1000 PD during these time periods was statistically significant for ceftriaxone (95% CI, 6.3-23.9; P=0.001) and vancomycin (95% CI, 1.2-18.1; P=0.03). For time period [C] to [D], there was a statistically significant reduction in mean DOT/1000 PD seen in overall antimicrobial use (95% CI, 156.9-313.6; P< 0.0001). Statistically significant decreases in DOT/1000 patient days were also seen for cefepime (95% CI, 11.4-36.4; P< 0.0007), ceftriaxone (95% CI, 5.0-24.8; P=0.005), and vancomycin (95% CI, 6.1-23.1; P=0.002). No difference was seen for piperacillin-tazobactam or meropenem DOT from [C] to [D].

Figure 1. Hospital-Wide Monthly Days of Therapy per 1000 Patient Days

Conclusion

Active engagement with frontline providers via handshake stewardship offers a more successful approach to decreasing antimicrobial utilization. A greater reduction in overall antimicrobial utilization was seen when the ASP was led by a pharmacist-physician team compared to when it was pharmacist-led without a physician champion.

Disclosures

All Authors: No reported disclosures
1345. Impact of the COVID-19 Pandemic on Pediatric Ambulatory Antibiotic Use in an Academic Health System
Authors: Katz Sophie E , Spencer Hillary , Zhang Jim , Banerjee Ritu , Banerjee Ritu
Published: January 2021

Background

It is unclear how the COVID-19 pandemic has impacted outpatient pediatric antibiotic prescribing.

Methods

We compared diagnoses and antibiotic prescription rates for children pre- vs post-COVID-19 in 5 ambulatory settings affiliated with Vanderbilt University Medical Center: emergency department (ED), urgent care clinics (including pediatric-only after-hours clinics [AHC]s and walk-in clinics [WIC] for all ages), primary care clinics (PCC), and retail health clinics (RHC). Time periods were pre-COVID-19 3/1/19 – 5/15/19 (P1); and post-COVID-19 3/1/20 – 5/15/20 (P2). Diagnoses and percent of encounters with an antibiotic prescription were analyzed by encounter (in-person vs telemedicine [TMed]), clinic and provider type. We also interviewed 16 providers about perceived COVID-19 impact on pediatric ambulatory antibiotic prescribing. Student’s T and χ 2 tests were used as appropriate.

Results

The number of pediatric ambulatory visits was 16671 in P1 and 7010 in P2. There were no TMed visits in P1 vs 188 in P2 (2.7% of total P2 visits); 186 (99% of TMed visits) were in PCC (Table). In all settings, the number of encounters was lower in P2 vs P1 (p< 0.001). The percent of encounters with an antibiotic prescription was lower in P2 (32%) than in P1 (38.2%) (p< 0.001) (Table) overall and in all settings except RHCs. Only 14 (7.4%) TMed visits resulted in an antibiotic prescription. There were no differences in antibiotic prescribing rates by provider type. Diagnoses varied significantly between periods in all clinic types except the ED, with noninfectious diagnoses being higher in P2 vs P1 (Figure 1). Providers felt that COVID-19 led to fewer but sicker patients presenting for care, and variable impact on antibiotic prescribing (Figure 2).

Table. Percent of Encounters with an Antibiotic by Clinic Type, Pre- and Post-COVID-19

Figure 1. Diagnosis Rates by Clinic Type, Pre- and Post-COVID-19

Figure 2. Themes from Provider Interviews about perceived Impact of COVID-19 on Clinician Practice

Conclusion

The proportion of encounters with non-infectious diagnoses increased and antibiotic prescribing rates decreased significantly in all pediatric ambulatory settings post-COVID-19 except RHCs. Almost all TMed encounters occurred in the primary care setting, and few resulted in an antibiotic prescription. Providers felt they saw fewer patients and higher acuity of illness post COVID-19.

Disclosures

Hillary Spencer, MD, MPH, NIH (T32 grant support) (Grant/Research Support)
1346. Implementation of a Multidisciplinary 48 Hour Antibiotic Timeout in a Pediatric Population
Authors: Konold Victoria , Bhagat Palak , Pisano Jennifer , Pettit Natasha N , Choksi Anish , Nguyen Cynthia , Kumar Madan
Published: January 2021

Background

To meet the core elements required for antimicrobial stewardship programs, our institution implemented a pharmacy-led antibiotic timeout (ATO) process in 2017 and a multidisciplinary ATO process in 2019. An antibiotic timeout is a discussion and review of the need for ongoing empirical antibiotics 2-4 days after initiation. This study sought to evaluate both the multidisciplinary ATO and the pharmacy-led ATO in a pediatric population, compare the impact of each intervention on antibiotic days of therapy (DOT) to a pre-intervention group without an ATO, and to then compare the impact of the pharmacy-led ATO versus multidisciplinary ATO on antibiotic days of therapy (DOT).

Methods

This was a retrospective, pre-post, quasi-experimental study of pediatric patients comparing antibiotic DOT prior to ATO implementation (pre-ATO), during the pharmacy-led ATO (pharm-ATO), and during the multidisciplinary ATO (multi-ATO). The pre-ATO group was a patient sample from February-September 2016, prior to the initiation of a formal ATO. The pharmacy-led ATO was implemented from February-September 2018. This was followed by a multidisciplinary ATO led by pediatric residents and nurses from February-September 2019. Both the pharm-ATO and the multi-ATO were implemented as an active non-interruptive alert added to the electronic health record patient list. This alert triggered when new antibiotics had been administered to the patient for 48 hours, at which time, the responsible clinician would discuss the antibiotic and document their decision via the alert workspace. Pediatric patients receiving IV or PO antibiotics administered for at least 48 hours were included. The primary outcome was DOT. Secondary outcomes included length of stay (LOS) and mortality.

Results

1284 unique antibiotic orders (n= 572 patients) were reviewed in the pre-ATO group, 868 (n= 323 patients) in the pharm-ATO and 949 (n= 305 patients) in the multi-ATO groups. Average DOT was not significantly different pre vs post intervention for either methodology (Table 1). Mortality was similar between groups, but LOS was longer for both intervention groups (Table 1).

Impact of an ATO on DOT, Mortality and LOS

Conclusion

An ATO had no impact on average antibiotic DOT in a pediatric population, regardless of the ATO methodology.

Disclosures

All Authors: No reported disclosures
1347. Improved Antibiotic Prescribing Practices for Respiratory Infections Through Use of Computerized Order Sets and Educational Sessions in Pediatric Clinics
Authors: Zahlanie Yorgo , Mang Norman , Lin Kevin , Hynan Linda S , Prokesch Bonnie C
Published: January 2021

Background

The literature about comprehensive outpatient antimicrobial stewardship programs remains sparse. However, computerized clinical decision support systems (CDSSs) have shown promising effectiveness in improving outpatient antibiotic prescribing.

Methods

We developed an intervention in the form of EPIC order sets comprised of outpatient treatment pathways for 3 pediatric bacterial acute respiratory infections or ARIs (otitis media, community-acquired pneumonia, and streptococcal pharyngitis) coupled with educational sessions. Two study periods were included, and 4 pediatric clinics were randomized into intervention and control arms. Education was provided to the 2 intervention clinics between the study periods, and EPIC order sets became available to these 2 clinics at the beginning of the post-intervention period. The primary endpoint was the rate of first-line antibiotic prescribing, and the secondary endpoints included antibiotic duration and antibiotic prescription modification within 14 days.

Results

A total of 2690 antibiotic prescriptions were written for bacterial ARIs. At pre-intervention, there was no difference between the study arms in terms of first-line antibiotic prescribing (74.9% vs. 77.7%, P=0.211) and antibiotic duration (9.69 ±0.96 days vs. 9.63 ±1.07 days, P>0.999). Following the intervention, the intervention clinics had higher rate of first-line antibiotic prescribing (83.1% vs. 77.7%, P=0.024) and shorter antibiotic duration (9.28 ±1.56 days vs. 9.79 ±0.75 days, P< 0.001) compared to the control clinics. The rate of modified antibiotics was small in all clinics (1.1-1.6%) and not different at pre-intervention (P=0.852) and post-intervention (P=0.552).

Analysis of categorical variables

Analysis of continuous variables

Distribution of the antibiotic prescriptions among the 3 bacterial acute respiratory infections

Conclusion

A computerized CDSS involving treatment pathways in the form of order sets coupled with educational sessions was associated with a higher rate of first-line antibiotic prescribing and shorter antibiotic duration for the outpatient treatment of bacterial ARIs. More studies are needed in order to assess the utility of multimodal approaches in pediatric outpatient antimicrobial stewardship.

Disclosures

All Authors: No reported disclosures
1348. Indirect Standardization to Improve Comparison of Children’s Hospitals’ Antimicrobial Use
Authors: Wattier Rachel , Thurm Cary , Banerjee Ritu , Banerjee Ritu , Hersh Adam
Published: January 2021

Background

Antimicrobial use (AU) measured by days of therapy per 1000 patient-days (DOT/1000pd), the most established metric, varies widely between children’s hospitals despite robust adoption of antimicrobial stewardship. Differences in diagnoses and procedures (case mix) between hospitals are a source of AU variation not included in adjustment methods such as the Standardized Antimicrobial Administration Ratio. In this study, we evaluated an indirect standardization method to adjust children’s hospital AU for case mix.

Methods

This multicenter retrospective cohort study included 51 children’s hospitals participating in the Pediatric Health Information System database from 2016-2018. All inpatient, observation, and neonatal admissions were included, with a total of 2,558,948 discharges. Hospitalizations were grouped into 83 strata defined based on All Patients Refined Diagnosis Related Groups (APR-DRGs). Observed to expected (O:E) ratios were calculated by indirect standardization of mean antibiotic DOT per case, with expected values from 2016-2018 and observed values from 2018, and compared to DOT/1000pd. Outlier hospitals were defined by O:E z-scores corresponding to below 10th percentile (low outlier) and above 90th percentile (high outlier).

Results

Antibacterial DOT/1000pd ranged from 345 to 776 (2.2-fold variation from lowest to highest), whereas O:E ratios ranged from 0.8 to 1.14 (1.4-fold variation from lowest to highest) (Figure 1). O:E ratios were moderately correlated with DOT/1000pd (correlation estimate 0.45; 95% CI 0.19-0.64; p=0.0008). Three high outlier hospitals and 6 low outlier hospitals were identified. Examining hospitals with comparably high DOT/1000pd but discordant O:E ratios, differences could be explained by variation in both case mix and condition-specific AU within strata defined by APR-DRGs.

Figure 1. Individual hospitals labeled on the X-axis, ordered by level of antibacterial DOT/1000pd (left axis), represented by bars. Diamonds represent O:E ratios derived by indirect standardization (right axis). Outlier hospitals (low and high) are highlighted in yellow. Dashed horizontal lines represent 10th percentile (lower) and 90th percentile (upper) limits of the O:E ratio distribution.

Conclusion

The observed variation in DOT/1000pd between hospitals is reduced when indirect standardization is applied to account for case mix differences. This approach can be adapted for more specific uses including clinical conditions, patient populations, or antimicrobial agents. Indirect standardization may enhance stewardship efforts by providing adjusted comparisons that incorporate case mix differences between hospitals.

Disclosures

All Authors: No reported disclosures
1349. Institutional Antibiograms Are Insufficient to Guide Clindamycin Use in Pediatric Skin and Soft Tissue Infections
Authors: Firmani Sarah E , Molloy Leah , Trivedi Gaurangi , Abdel-Haq Nahed M
Published: January 2021

Background

Clindamycin (CLN) is a common empiric antimicrobial for pediatric skin and soft tissue infections (SSTI) despite decreasing susceptibility of Staphylococcus aureus (SA) to CLN on institutional antibiograms. This study inquired whether institutional antibiograms are an accurate representation of susceptibility for these infections. It also attempted to find patient and infection characteristics associated with being clindamycin susceptible (CLN-S).

Methods

This was a retrospective chart review of children with community-acquired (CA) SA infections in 2016 and 2017. A Staphylococcus aureus antibiogram was created based on infection type. Various patient and infection characteristics were compared between CLN-S and clindamycin-resistant (CLN-R) isolates to identify predictors of being CLN-S via binary logistic regression. Characteristics with p < 0.2 from a univariate analysis (chi-square or Fisher’s exact test) were included in the regression; p < 0.05 after the regression was considered statistically significant.

Results

362 SA infections were included. These were 76% CLN-S, similar to the institutional antibiogram (79% CLN-S, p = 0.168). MSSA CLN susceptibility was lower than the antibiogram (71% vs. 79% CLN-S, p = 0.042). MRSA susceptibility was similar (79% vs. 80% CLN-S, p = 0.859). Infection types assessed were abscess (n = 264, 81% CLN-S), osteomyelitis (n = 40, 75% CLN-S), lymph node (n = 16, 75% CLN-S), staphylococcal scalded skin syndrome (n = 9, 56% CLN-S), eczema superinfection (n = 17, 53% CLN-S), bullous impetigo (n = 7, 40% CLN-S), and non-bullous impetigo (n = 7, 29%). Characteristics found to be associated with being CLN-S included abscess (OR 3.883, p = 0) and high white blood cell count (OR 2.482, p = 0.001). Characteristics associated with CLN-R included contact to person with abscess (OR 0.468, p = 0.035) and hypotension during infection (OR 0.312, p = 0.005).

Conclusion

The use of institutional antibiograms to guide CLN susceptibility in CA SA infections may be limited by the type of infection, patient characteristics, and the likelihood of MSSA vs. MRSA infection. In our patients, having an abscess was associated with CLN-S. Empiric therapy of CA SA infections in children should not be driven solely by institutional antibiograms.

Disclosures

All Authors: No reported disclosures
1351. Pediatric Antibioitic Use in the North Carolina Medicaid Population
Authors: Young Rebecca R , Lantos Paul , Lantos Paul , Smith Michael J
Published: January 2021

Background

Antimicrobial resistance is increasing in the United States, with antibiotic use as the main driver. The majority of antibiotic use occurs in the outpatient setting. 6 of the 7 highest prescribing states are located in the Appalachian region of the country. Overall, the state of North Carolina (NC) has prescribing rates that are at the national average, but the geographic, patient and provider-level characteristics associated with antibiotic prescribing within the state are unknown.

Methods

We used NC Medicaid claims from 2013-2018 to identify oral antibiotics prescribed to children, defined as individuals < 21 years. Antibiotics were identified using National Drug Codes. Overall rates of antibiotic prescribing were reported as the number of prescriptions per 1000 children overall and stratified by age, sex, race/ethnicity and residence in a metropolitan area. Provider characteristics and setting type were identified using existing variables in the Medicaid dataset. A geographic information system was used to graphically depict rates of antibiotic use by county.

Results

Rates of prescribing decreased from 724/1000 children in 2013 to 578/1000 children in 2018. Across all study years there were differences in prescribing rates by sex, race/ethnicity, age and residence in a metropolitan area. (Table) Prescriptions were more common in children who were younger (0-2), white non-Hispanic, female and living in non-metropolitan areas. Prescribing rates were geographically heterogeneous, with the highest rates in the western mountain region and declining across a west to east gradient. (Figure) Most (62%) antibiotic prescriptions were written in the primary care setting. Pediatricians prescribed 48% of all antibiotic courses.

Antibiotic Prescriptions Per 1000 Children, by Demographic Group (2013-2018)

Antibiotic Prescriptions per 1000 Children, by County (2013-2018)

Conclusion

Although NC is not a high-prescribing state in general, we found notable difference in prescribing based on key demographic characteristics. These results are consistent with prior reports from other Appalachian states including Kentucky, West Virginia and Tennessee. Rates of prescription were highest in non-metropolitan areas overall but GIS mapping revealed a marked west-east gradient. These data suggest that specific Appalachian characteristics, rather than rurality alone, may be associated with excessive antibiotic prescribing.

Disclosures

Michael J. Smith, MD, MSC.E, Kentucky Medicaid (Grant/Research Support)Merck (Grant/Research Support)