Fluoroquinolone Use Among Hospitalized Children: Diagnosis-Based Stratification to Identify Stewardship Targets.

Background: As FQ (fluoroquinolone) use has shifted in pediatric populations, better metrics are needed to guide targeted antibiotic stewardship interventions and limit development of adverse events and resistance, particularly in medically complex children. In this study, we identify high-utilization groups based on underlying medical conditions and describe their relative FQ use over time. Methods: This study is a retrospective analysis of data from the Pediatric Health Information System database from 2016 to 2020. We identify high-utilization groups based on underlying medical conditions using International Classification of Diseases, Ninth or Tenth Revision codes. We delineate overall trends in the use of FQs in the inpatient setting, including rate and proportional use by each patient group. Results: Patients with an oncology diagnosis represent a large (25%-44%) and rising proportion (+4.8%/year, P = .001) of national FQ use over the study period. Patients with intra-abdominal infections, including appendicitis, have had a significant increase in both their relative proportional use of FQs (+0.6%/year, P = .037) and proportion of FQ use per admission encounter over the study period (+0.6%/year, P = .008). Patients with cystic fibrosis represent a decreasing proportion of overall use (-2.1%/year, P = .011) and have decreasing FQ use per inpatient encounter (-0.8%/year, P = .001). Conclusions: Patients with an oncology diagnosis and patients with an intra-abdominal infection appear to be targets for FQ stewardship. Patients with cystic fibrosis have decreasing inpatient FQ use. Key Points: This study describes fluoroquinolone use among hospitalized children from 2016 to 2020, stratified by underlying diagnoses. These trends are used to identify high-yield antibiotic stewardship targets.

Sociodemographic Comparison of Children With High-risk Medical Conditions Referred vs Identified Through Screening Plus Outreach for COVID-19 Therapeutics.

Importance: Minoritized groups are less likely to receive COVID-19 therapeutics, but few studies have identified potential methods to reduce disparities. Objective: To determine whether screening plus outreach, when compared with referral alone, increases identification of vulnerable pediatric patients at high risk for severe disease eligible for COVID-19 therapeutics from low-resourced communities. Design, Setting, and Participants: A retrospective cohort study of COVID-19 medication allocation between January 1, 2022, and February 15, 2022, at Lurie Children's Hospital, a quaternary care children's hospital, in Chicago, Illinois. The cohorts were pediatric patients referred for COVID-19 therapeutics or with a positive SARS-CoV-2 polymerase chain reaction within the hospital system followed by outreach. Screening involved daily review of positive cases of SARS-CoV-2, followed by medical record review for high-risk conditions, and communication with clinicians and/or patients and families to offer therapy. Exposures: Diagnosis of COVID-19. Main Outcomes and Measures: The primary measure was difference in child opportunity index (COI) scores between the 2 cohorts. Secondary measures included presence and duration of symptoms at diagnosis, medication uptake, race and ethnicity, insurance type, qualifying medical condition, sex, primary language, and age. Results: Of 145 total patients, the median (IQR) age was 15 (13-17) years, and most were male (87 participants [60.0%]), enrolled in public insurance (83 participants [57.2%]), and members of minoritized racial and ethnic groups (103 participants [71.0%]). The most common qualifying conditions were asthma and/or obesity (71 participants [49.0%]). From 9869 SARS-CoV-2 tests performed, 94 eligible patients were identified via screening for COVID-19 therapeutics. Fifty-one patients were identified via referral. Thirty-two patients received medication, of whom 8 (25%) were identified by screening plus outreach alone. Compared with referred patients, patients in the screening plus outreach group were more likely to have moderate, low, or very low COI composite scores (70 patients [74.5%] vs 27 patients [52.9%]); public insurance (65 patients [69.1%] vs 18 patients [35.3%]); and asthma or obesity (60 patients [63.8%] vs 11 patients [21.6%]). Patients in the referral group were more likely to be non-Hispanic White (23 patients [45.1%] vs 19 patients [20.2%]) and receive medication (24 patients [47.1%] vs 8 patients [8.5%]). Conclusions and Relevance: Compared with referral patients, screening plus outreach patients for COVID-19 medications were more socially vulnerable, with lower COI scores, and more likely to have asthma or obesity. Future studies should investigate communication strategies to improve uptake of these medications after outreach.

Drivers of Prolonged Outpatient Antibiotic Therapy for Urinary Tract Infections and Community-Acquired Pneumonia.

BACKGROUND: Variability exists in treatment duration for community-acquired pneumonia (CAP) and urinary tract infection (UTI) in children and may be associated with non-clinical factors. METHODS: A retrospective study was conducted of patients treated for outpatient CAP and UTI in a children's hospital network from 2016 to 2019. Multivariable logistic regression was performed to identify predictors of long antibiotic duration (≥10 days). Hospitalization within 30 days was determined. RESULTS: Overall, 2124 prescriptions for CAP and 1116 prescriptions for UTI were included. Prescriptions were ≥10 days in 59.9% and 47.6% for CAP and UTI, respectively. Long durations were more common in the emergency department (ED) than in clinics for UTI's (P = .0082), and more common in convenient care for CAP (P = .045). In UTI's, Asian and Hispanic patients received shorter durations than white patients. Younger children had greater odds of long duration for both diagnoses. Medicaid insurance was associated with long therapy for UTI (OR: 1.660, P = .0042) and CAP (OR: 1.426, P = .0169). Residents and fellows were less likely to give long durations than attending physicians (P < .0001). APNs were more likely to administer long therapies in CAP (P = .0062). Subsequent hospitalizations were uncommon for UTI (n = 10) and CAP (n = 20). CONCLUSIONS: Younger age, Medicaid insurance, ED, and convenient care visits were associated with a long duration of therapy. Residents and fellows were less likely to give long durations.

Documentation of Indications: Agreement Between Order Entry and Clinical Notes and Effect on Time to Antibiotic Administration.

BACKGROUND/OBJECTIVES: Antibiotic indication documentation at the time of order entry is mandated by the Joint Commission. Inclusion of indication at order entry may have an impact on the time to administration. Our primary objective was to evaluate agreement between indication selected during order entry and clinical notes. Our secondary objective was to observe if there was a change in time to administration after indications were required during order entry. METHODS: Patients ≤18 years old who received ≥1 dose of vancomycin or ceftriaxone during a preintervention period and 3 postintervention periods were included. Indication for use, agreement between order and clinical note, and timing of antibiotic administration were collected. RESULTS: Most common indication for vancomycin (total: 789) was sepsis (26%, n = 204). Common indications for ceftriaxone (total: 1071) were sepsis (12%, n = 127), perforated appendicitis (12%, n = 125), and urinary tract infection (10%, n = 107). Postintervention, agreement between the indication selected during order entry and indication documented in clinical note for ceftriaxone and vancomycin orders were 41% and 46%, respectively. Median time to administration decreased among patients who received ceftriaxone (P < .01) but had no significant impact on time to administration of vancomycin (P = .49). CONCLUSIONS: Indication for ceftriaxone and vancomycin selected during order entry and reported in clinical notes inconsistently matched. Inclusion of antibiotic indication may impact time to administration.

Use of the Electronic Health Record to Optimize Antimicrobial Prescribing.

PURPOSE: This review summarizes how interventions in the electronic health record (EHR) can optimize antimicrobial stewardship across the continuum of antimicrobial decision making, from diagnosis of infection to discontinuation of therapy. In addition, opportunities to optimize provider communication and patient education are identified. METHODS: A narrative review was conducted to identify how interventions in the EHR can influence antimicrobial prescribing behavior. Examples from pediatrics were specifically identified. Interventions were then categorized into high-impact/low-effort, high-impact/high-effort, and low-impact/low-effort groupings based on historical experience. FINDINGS: EHR-based interventions can be used for stratifying patients at risk for infection and are useful in identifying patients with new-onset infections. Additional tools include automatically updated antibiograms tailored to specific patient populations, timely authorization of restricted antimicrobials, and more accurate allergy labeling. Medical errors can be reduced and communication between providers can be improved by standardized data fields. Clinical decision support tools can guide appropriate selection of therapy, and visual prompts can reduce unnecessarily prolonged therapy. Benchmarking of antimicrobial use, tailored patient education, and improved communication during transitions of care are enhanced through EHR-based interventions. IMPLICATIONS: Prescribing behavior can be modified through a range of interventions in the EHR, including tailored education, alerts, prompts, and restrictions on provider behavior. Further studies are needed to compare the effectiveness of various strategies.

Amphotericin-Associated Infusion-Related Reactions: A Narrative Review of Pre-Medications.

PURPOSE: Amphotericin B has been reported to cause infusion-related adverse effects (IRAEs). To prevent IRAEs, pre-medications may be administered prior to the administration of amphotericin B. The effects of different formulations of amphotericin B (amphotericin B deoxycholate and lipid formulations), duration of infusion, and utility of pre-medications in preventing IRAEs are reviewed. METHODS: PubMed, Ovid Medline, Embase, Web of Science, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and the Scopus databases were searched with the following search terms: pre-medication, amphotericin B, and its related compounds. Upon review, a total of 39 publications were considered for inclusion. FINDINGS: In vitro and in vivo studies have reported that amphotericin B deoxycholate stimulates pro-inflammatory cytokine genes causing IRAEs. Nonetheless, the clinical literature has reported that IRAEs occur among patients who received pre-medications. In comparison to amphotericin B deoxycholate, lipid-based formulations of amphotericin may result in a lower or similar risk for IRAEs. IMPLICATIONS: The routine use of pre-medications to prevent IRAEs after the administration of amphotericin B (amphotericin B deoxycholate or lipid formulations) would not be warranted.

Opportunities for Antimicrobial Stewardship Among Pediatric Patients Prescribed Combination Antifungal Therapy.

OBJECTIVE: Combination antifungal therapy (CAF) may be prescribed to treat invasive fungal infections (IFIs). Data on the incidence of CAF among the pediatric population are limited. Antimicrobial stewardship for CAF includes therapeutic drug monitoring (TDM) and monitoring for adverse events. Primary outcome was to determine the incidence of CAF prescribed for documented proven, probable, and possible IFI. Secondary outcomes were to determine initial dose of antifungal therapy, determine incidence of adverse events, and evaluate our practice of TDM. METHODS: Medical charts of patients who received CAF for proven, probable, or possible IFI within 6 years were reviewed. Patients age ≤18 years, prescribed CAF (defined as a second antifungal therapy started ≤72 hours of initial antifungal therapy) for at least 72 hours, and with normal liver function test results were included. RESULTS: 57 patients received CAF for 72 separate episodes: 35 episodes were proven IFI, 11 were probable IFI, and 26 were possible IFI. Initial dose of antifungal therapy varied, and 29.1% received a loading dose. A total of 10 patients experienced 14 adverse events that were related to antifungal therapy. In 63.8% of CAF episodes, TDM was conducted. Target antifungal concentrations were documented for 10 CAF episodes. Reason for discontinued of CAF was documented for 35 episodes. Of these episodes, 74% were discontinued after therapeutic antifungal concentrations were achieved. CONCLUSIONS: There are opportunities for antimicrobial stewardship interventions in the method of TDM and monitoring for adverse events that could aid in management of CAF.

Short-Duration Electronic Health Record Option Buttons to Reduce Prolonged Length of Antibiotic Therapy in Outpatients.

BACKGROUND: Prolonged antibiotic therapy may be associated with increased adverse events and antibiotic resistance. We deployed an intervention in the electronic health record (EHR) to reduce antibiotic duration for pediatric outpatients. METHODS: A preintervention and postintervention interrupted time series analysis of antibiotic duration for 7 antibiotics was performed for patients discharged from the ED and clinics of a children's hospital network from 2012 to 2018. In February 2015, clickable 5- and 7-day duration option buttons were deployed in the EHR for clindamycin, cephalexin, ciprofloxacin and levofloxacin, trimethoprim-sulfamethoxazole, amoxicillin, and cefdinir, with an additional 10-day option for the latter 2. Prescribers were able to enter a free-text duration. The option buttons were not announced, and were not linked to a specific diagnosis or quality improvement initiative. The primary outcome was proportion of prescriptions per month with duration of 10 days. Balancing secondary outcomes were reorders of the same agent, return to clinic, and inpatient admissions within 30 days. RESULTS: There were 54 315 prescriptions for the 7 antibiotics associated with 39 894 patients, 18 683 clinic visits, and 35 632 ED visits. Overall, a -5.1% (95% confidence interval [CI], -8.3% to -2.0%) change in the proportion of prescriptions with a 10-day duration was attributable to the intervention, with larger effects noted for clindamycin (-20.8% [95% CI, -26.9% to -14.7%]) and cephalexin (-9.9% [95% CI, -14.3% to -5.4%]). There was no increase in the reorders of the same agent, return clinical encounters, or inpatient admissions within 30 days. CONCLUSIONS: A simple intervention in the EHR can safely reduce duration of antibiotic therapy.

Clinical Performance and Impact of Accelerate Pheno for Gram-negative Bacteremia in Hospitalized Children.

PURPOSE: Accelerate Pheno provides rapid identification and antimicrobial susceptibility tests (ASTs) of pathogens that cause blood stream infections (BSIs). The study objective was to assess the accuracy of the Accelerate Pheno platform and its impact on antimicrobial modification in children with gram-negative BSIs. METHODS: A retrospective review was conducted of patients at a children's hospital with gram-negative BSIs from November 2018 to November 2019. Proportion of agreement between Accelerate Pheno and standard of care (SOC) was determined for organism identification (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) and susceptibilities (MicroScan). Time from culture collection to Gram stain, identification and AST by the Accelerate Pheno method, and AST results by MicroScan were calculated. Antibiotic modifications and opportunities to optimize antimicrobial stewardship were recorded. FINDINGS: Of 115 BSIs from 90 patients, 90 monomicrobial gram-negative BSIs with an organism included on the Accelerate Pheno panel were found. Compared with SOC, the organism was correctly identified in 90 patients (100%). Overall, 5 of 732 ASTs (0.7%) reported susceptible by Accelerate Pheno were resistant by SOC, and 8 of 109 (7.3%) reported resistant by Accelerate Pheno were susceptible by SOC. On the basis of the Accelerate Pheno AST results, antibiotic spectrum was increased in 10 of 11 instances to correct organism-drug mismatch and narrowed in 16 of 33 instances. Median times from culture collection to reporting of Gram stain, Accelerate Pheno identification, Accelerate Pheno AST, and SOC AST were 12.6, 14.6, 19.9, and 60.6 h, respectively. Median time to optimal therapy was 21.8 h for infections with actionable AST data. IMPLICATIONS: Accelerate Pheno was accurate and decreased time to optimal therapy by almost 40 h for children with gram-negative BSIs. Antibiotic spectrum was increased in multiple instances, but opportunities to decrease spectrum were underused.

Fidaxomicin for the treatment of Clostridioides difficile in children.

Fidaxomicin is an oral narrow-spectrum novel 18-membered macrocyclic antibiotic that was initially approved in 2011 by the US FDA for the treatment of Clostridioides difficile infections (CDI) in adults. In February 2020, the FDA approved fidaxomicin for the treatment of CDI in children age >6 months. In adults, fidaxomicin is as efficacious as vancomycin in treating CDI and reduces the risk of recurrent CDI. An investigator-blinded, randomized, multicenter, multinational clinical trial comparing the efficacy and safety of fidaxomicin with vancomycin in children was recently published confirming similar findings as previously reported in adults. Fidaxomicin is the first FDA-approved treatment for CDI in children and offers a promising option for reducing recurrent CDI in this population.

Utilizing the electronic health record to construct antibiograms for previously healthy children with urinary tract infections.

Traditional antibiograms can guide empiric antibiotic therapy, but they may miss differences in resistance across patient subpopulations. In this retrospective descriptive study, we constructed and validated antibiograms using International Classification of Disease, Tenth Revision (ICD-10) codes and other discrete data elements to define a cohort of previously healthy children with urinary tract infections. Our results demonstrate increased antibiotic susceptibility. This methodology may be modified to create other syndrome-specific antibiograms.

Evaluation of Risk Factors for Clostridium difficile Infection in Hematopoietic Stem Cell Transplant Recipients.

STUDY OBJECTIVES: The primary objective was to determine the impact of hematologic malignancies and/or conditioning regimens on the risk of developing Clostridium difficile infection (CDI) in patients undergoing hematopoietic stem cell transplantation (HSCT). Secondary objectives were to determine if traditional CDI risk factors applied to patients undergoing HSCT and to determine the presence of CDI markers of severity of illness among this patient population. DESIGN: Single-center retrospective case-control study. SETTING: Quaternary care academic medical center. PATIENTS: A total of 105 patients who underwent HSCT between December 2009 and December 2014; of these patients, 35 developed an initial episode of CDI (HSCT/CDI group [cases]), and 70 did not (controls). Controls were matched in a 2:1 ratio to cases based on age (± 10 yrs) and date of HSCT (± 6 mo). MEASUREMENTS AND MAIN RESULTS: Baseline characteristics of the two groups were well balanced regarding age, sex, race, ethnicity, and type of HSCT. No significant differences in conditioning regimen, hematologic malignancy, total body irradiation received for HSCT, use of antibiotics within 60 days of HSCT, or use of prophylactic antibiotics after HSCT were noted between the two groups. Patients in the control group were 10.57 (95% confidence interval 1.24-492.75) more likely to have received corticosteroids prior to HSCT than patients in the HSCT/CDI group (p=0.01). Use of proton pump inhibitors at the time of HSCT was greater among the control group than among patients in the HSCT/CDI group (97% vs 86%, p=0.048). No significant difference in mortality was noted between the groups at 3, 6, and 12 months after HSCT. Metronidazole was frequently prescribed for patients in the HSCT/CDI group (34 patients [97%]). Severe CDI was not common among patients within the HSCT/CDI group (13 patients [37%]); vancomycin was infrequently prescribed for these patients ([31%] 4/13 patients). CONCLUSION: Hematologic malignancies and a conditioning regimen administered for HSCT were not significant risk factors for the development of CDI after HSCT. Use of corticosteroids prior to HSCT and use of proton pump inhibitors at the time of HSCT were associated with a significantly decreased risk of CDI.

Bacterial and viral co-infections complicating severe influenza: Incidence and impact among 507 U.S. patients, 2013-14.

BACKGROUND: Influenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection. OBJECTIVES: To describe the spectrum and clinical impact of co-infections. STUDY DESIGN: Retrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis. RESULTS: Of 507 adult and pediatric patients, 114 (22.5%) developed bacterial co-infection and 23 (4.5%) developed viral co-infection. Staphylococcus aureus was the most common cause of co-infection, isolated in 47 (9.3%) patients. Characteristics independently associated with the development of bacterial co-infection of adult patients in a logistic regression model included the absence of cardiovascular disease (OR 0.41 [0.23-0.73], p=0.003), leukocytosis (>11K/µl, OR 3.7 [2.2-6.2], p<0.001; reference: normal WBC 3.5-11K/µl) at ICU admission and a higher ICU admission SOFA score (for each increase by 1 in SOFA score, OR 1.1 [1.0-1.2], p=0.001). Bacterial co-infections (OR 2.2 [1.4-3.6], p=0.001) and viral co-infections (OR 3.1 [1.3-7.4], p=0.010) were both associated with death in bivariable analysis. Patients with a bacterial co-infection had a longer hospital stay, a longer ICU stay and were likely to have had a greater delay in the initiation of antiviral administration than patients without co-infection (p<0.05) in bivariable analysis. CONCLUSIONS: Bacterial co-infections were common, resulted in delay of antiviral therapy and were associated with increased resource allocation and higher mortality.

Inhaled Antibiotics for Gram-Negative Respiratory Infections.

Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

Severe Influenza in 33 US Hospitals, 2013-2014: Complications and Risk Factors for Death in 507 Patients.

BACKGROUND: Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013-2014 influenza season. Little is known about the epidemiology of severe influenza during this season. METHODS: A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes. RESULTS: A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4-6.9], P=.006 and 50-64 years, 2.5 [1.3-4.9], P=.007; reference age 18-49 years), male sex (1.9 [1.1-3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9-37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2-1.4], P<.001). CONCLUSION: Risk factors for death among US patients with severe influenza during the 2013-2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.