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The article in the Journal of Infectious Diseases responds to the importance of quality measures specific to infectious diseases, particularly focusing on children. It emphasizes the need to track and improve the quality of care for pediatric populations, who face unique health challenges. The proposed guidelines center on antimicrobial stewardship, highlighting the critical importance of judicious antibiotic use in children to prevent adverse events and promote optimal health outcomes. The article suggests expanding quality improvement metrics to include children of all ages to address the diverse needs of the US population and improve health outcomes across the lifespan. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Combination antifungal therapy (CAF) is often prescribed to treat invasive fungal infections, despite equivocal data showing benefit. We evaluated number of CAF for treatment of proven, probable and possible invasive fungal infection (IFI) in hospitalized children, associated adverse effects (AE), and use of therapeutic drug monitoring (TDM). Methods Medical charts of patients ≤ 18 years old that received CAF for ≥72 hours with normal liver function test between 1/1/13 through December 31/18 were reviewed. Patients could be included for multiple episodes of CAF. Data included primary site of IFI, host risk factors, demonstration of fungal elements in tissue/sterile sites, clinical and mycological criteria for IFI (defined by European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group), CAF regimen, incidence of TDM, and AE. Results Overall, 73 episodes of IFI were reviewed [unique patients (n) =60]. The median age was 10 years. Majority (61.6%) of patients were diagnosed with a hematological malignancy (n = 20 acute lymphoblastic leukemia, n = 12 acute myeloid leukemia, n = 5 aplastic anemia). A number of proven, possible, probable IFI were 36, 27 and 20, respectively (Table 1). Most frequent organism isolated in proven IFI was Aspergillus fumigatus (episodes=5, n = 4). Most common primary site of IFI was pulmonary (episodes=32, n = 27). Median days of CAF was 6.8 (range: 3–170). Sixty-six episodes included treatment with a triazole-containing regimen (90%). TDM was conducted in 51 (77%) episodes of triazole-containing regimens. AE were reported in 14 episodes (n = 10) (infusion-related reactions and nephrotoxicity reported in 4 episodes each, electrolyte abnormalities and skin reaction reported in 2 episodes each, and liver dysfunction and hypersensitivity reported in 1 episode each). Conclusion Patients diagnosed with proven or probable IFI received a longer duration of CAF in comparison to possible IFI. Voriconazole was frequently prescribed in combination with either micafungin or liposomal amphotericin B for IFI. Antifungal stewardship opportunities exist to improve TDM and reduce the incidence of AE when prescribing CAF. Disclosures All authors: No reported disclosures [ABSTRACT FROM AUTHOR]

Background Joint Commission mandates that prescribers document indication for antibiotics at the time of prescribing. Antibiotic indications may offer opportunities for pharmacists to optimize dosing and frequency or provide alternative therapeutic options. We examined the impact of antibiotic indications during order entry on frequency and type of pharmacist interventions, time to order verification, and time to administration of antibiotics. Methods Number of pharmacist interventions documented in EPIC from 4/28/17 through 4/28/18 (pre-intervention) were compared with interventions from 4/29/18 through 2/28/19 (post-intervention). All pharmacist interventions involving antibiotic orders were included. For antibiotic orders involving a pharmacist intervention, data collected included antibiotic prescribed, indication for antibiotic (post-intervention only) and reason for intervention. For administered antibiotics, data collected included order time, time of arrival of order in pharmacist queue, pharmacist verification time, patient administration time. Statistical analysis involved chi-squared test (compare the reason for intervention) and t-test (compare difference in time). Results There were 790 orders and 638 orders that involved a pharmacist's interventions, pre-intervention and post-intervention, respectively (Tables 1 and 2). Pre-intervention, there were 200 antibiotic orders that had a documented pharmacist intervention and were administered. Post-intervention, there were 184 orders that had a documented pharmacist intervention and were administered. Abdominal/pelvic (29 orders, 16%), sepsis (19 orders, 10%), and surgical prophylaxis (18 orders, 9.7%) were the most frequent indications selected during order entry. Average time to order verification was 119 minutes pre-intervention and 123 minutes post-intervention (P =0.97). Average time to administration of antibiotics was 313 minutes and 360 minutes pre-intervention and post-intervention, respectively (P =0.45). Conclusion Inclusion of the selection of antibiotic indications during order entry did not significantly impact the number of pharmacist interventions, time to order verification nor time to administration. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Limited data are available on non-β-lactam (NBL) antibiotic allergy labeling in children. Understanding the incidence and patterns of NBL labeling is important as NBL hypersensitivity testing lacks standardization and false labeling may constrain therapeutic options and compromise antimicrobial stewardship. Methods We conducted a retrospective review of patients at our tertiary care pediatric facility and associated clinics who had first reported allergy to NBL antibiotics from January 1, 2015 to December 31, 2015. Demographic data, NBL subclass, severity, description of reaction, and ICD-9/10 diagnostic codes were recorded. In addition, subsequent antibiotic during the following 3 years (2016–2018) was determined. NBL allergy descriptions, when reported, were categorized based on severity and type of reaction. Results Of 35,796 patients with first clinical encounters in 2015, 223 patients (0.6%) had at least one NBL allergy reported, 1370 (3.8%) had a β-lactam allergy reported, and 101 (0.3%) patients had both an NBL and β-lactam allergy. There were 16 patients with two NBL allergies. The median age of patients with NBL allergy was 9.0 years. NBL classes and allergic reaction types are listed in the tables. Chronic conditions of patients with NBL allergy included gastrointestinal disease (n = 51), neurological disease (n = 37), malignancy (n = 36), bone marrow or solid-organ transplant (n = 4), and cystic fibrosis (n = 5). In the subsequent 3 years, 28 patients with NBL allergies received 129 systemic courses of antibiotics as inpatients, including 8 patients who received ≥10 courses. Conclusion Although not as common as β-lactam allergies, NBL allergies were noted in a substantial number of new patients. When described, the majority of patients did not have severe reactions, and were most likely nonallergic adverse reactions. As many of the patients have chronic conditions and require subsequent antibiotics, adjudication of true allergy status may be beneficial. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

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.

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.

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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)