urations of antibiotic treatment for acute otitis media and variability in prescribed durations across two large academic health systems.

BACKGROUND: Acute otitis media (AOM) accounts for roughly 25% of antibiotics prescribed to children annually. Despite national guidelines that recommend short (5-7 days) durations of antibiotics for children two years and older with AOM, most receive long (10-day) courses. This study aims to evaluate antibiotic durations prescribed for children aged 2-17 years with uncomplicated AOM across two pediatric academic health systems, and to assess the variability in prescribed durations between and within each system. METHODS: Electronic medical record (EMR) data from 135 care locations at two health systems were retrospectively analyzed. Outpatient encounters for children aged 2-17 years with a diagnosis of AOM from 2019-2022 were included. The primary outcome was the percent of 5-day prescriptions. Secondary outcomes included the proportion of 7-day prescriptions, 10-day prescriptions, prescriptions for non-first line antibiotics, cases associated with treatment failure, AOM recurrence, and adverse drug events. RESULTS: Among 73,198 AOM encounters for children 2 years and older, 61,612 (84%) encounters resulted in an antibiotic prescription. Most prescriptions were for 10 days (45,689; 75%), 20% were for 7 days (12,060), and only 5% were for 5 days (3,144). Treatment failure, AOM recurrence, adverse drug events, hospitalizations, and office, emergency department or urgent care visits for AOM within 30 days after the index visit were rare. CONCLUSIONS: Despite national guidelines that recommend shorter durations for children with uncomplicated AOM, 75% of our cohort received 10-day durations. Shortening durations of therapy for AOM could reduce antibiotic exposure and should be a priority of pediatric antibiotic stewardship programs.

Antibiotic-associated neutropenia is marked by depletion of intestinal Lachnospiraceae in pediatric patients.

Hematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics and at the time of neutropenia. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and type of infection or type of antibiotic used; however intensive care unit admission and length of therapy were associated with neutropenia. Reduced intestinal microbiome richness and decreased abundance of Lachnospiraceae family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism and fatty acid metabolism that are known to be produced by Lachnospiraceae . Our study confirms a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis. As the microbiome is a key determinant of stem cell transplant and immunotherapy outcomes, these findings are likely to be of broad significance. Key Points: Neutropenia occurred in 17% of patients receiving prolonged antibiotic therapy.We found no association between neutropenia and type of infection or class of antibiotic used. Development of neutropenia after prolonged antibiotic treatment was associated with decreased prevalence of Lachnospiraceae and Lachnospiraceae metabolites such as citrulline.

Practice Versus Potential: The Impact of the BioFire FilmArray Pneumonia Panel on Antibiotic Use in Children.

BACKGROUND: The BioFire FilmArray Pneumonia Panel (BFPP), a multiplex PCR panel for the diagnosis of lower respiratory tract infections, has been proposed as a tool for antimicrobial stewardship. Few studies evaluate real-world implementation of the BFPP and no studies focus exclusively on children. Our institution implemented BFPP testing without restrictions. METHODS: We conducted a retrospective cohort study in children hospitalized at St. Louis Children's Hospital to (1) characterize the use of the BFPP in pediatric patients and (2) assess how results impacted antibiotic use. We included all BFPP tests obtained during the first year after the introduction of the test, September 2021 through August 2022. The primary outcome was change in antibiotic therapy within 24 hours of results, which was compared to the potential change in antibiotic therapy determined by two infectious diseases clinicians. RESULTS: One hundred sixty-nine tests from 126 patients were included. Nine patients were immunocompromised and 19 had chronic tracheostomy. The majority of tests were sent from tracheal aspirate specimens (92%) and from patients in an intensive care unit (94%). Only 51% of tests were obtained due to respiratory failure or suspected pneumonia. For 80% of test results, there was potential to change antibiotics, but change occurred in only 46% of tests in practice. Antibiotic escalation was more common (26%) than de-escalation (15%) or discontinuation (4.1%). CONCLUSIONS: In a cohort of pediatric patients tested with the BFPP, the majority of tests were sent from tracheal aspirates and less than half of tests were associated with a change in antibiotics.

Carbapenem-resistant Enterobacterales in Children at 18 US Health Care System Study Sites: Clinical and Molecular Epidemiology From a Prospective Multicenter Cohort Study.

Background: Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat in the United States. Objective: Describe the clinical and molecular epidemiology of CRE in a multicenter pediatric cohort. Methods: CRACKLE-1 and CRACKLE-2 are prospective cohort studies with consecutive enrollment of hospitalized patients with CRE infection or colonization between 24 December 2011 and 31 August 2017. Patients younger than age 18 years and enrolled in the CRACKLE studies were included in this analysis. Clinical data were obtained from the electronic health record. Carbapenemase genes were detected using polymerase chain reaction and whole-genome sequencing. Results: Fifty-one children were identified at 18 healthcare system study sites representing all U.S. census regions. The median age was 8 months, with 67% younger than age 2 years. Median number of days from admission to culture collection was 11. Seventy-three percent of patients had required intensive care and 41% had a history of mechanical ventilation. More than half of children had no documented comorbidities (Q1, Q3 0, 2). Sixty-seven percent previously received antibiotics during their hospitalization. The most common species isolated were Enterobacter species (41%), Klebsiella pneumoniae (27%), and Escherichia coli (20%). Carbapenemase genes were detected in 29% of isolates tested, which was lower than previously described in adults from this cohort (61%). Thirty-four patients were empirically treated on the date of culture collection, but only 6 received an antibiotic to which the CRE isolate was confirmed susceptible in vitro. Thirty-day mortality was 13.7%. Conclusions: CRE infection or colonization in U.S. children was geographically widespread, predominantly affected children younger than age 2 years, associated with significant mortality, and less commonly caused by carbapenemase-producing strains than in adults.

Diagnostic Stewardship for Next-Generation Sequencing Assays in Clinical Microbiology: An Appeal for Thoughtful Collaboration.

Next-generation sequencing (NGS)-based assays are primarily available from reference laboratories for diagnostic use. These tests can provide helpful diagnostic data but also can be overused by ordering providers not fully understanding their limitations. At present, there are few best practice guidelines for use. NGS-based assays can carry a high cost to institutions and individual patients, requiring thoughtful use through application of diagnostic stewardship principles. This article provides an overview of diagnostic stewardship approaches as applied to these assays, focusing on principles of collaboration, differential diagnosis formation, and seeking the best patient, syndrome, sample, timing, and test for improved patient care.

A comprehensive assessment of the prolonged febrile neutropenia evaluation in pediatric oncology patients.

BACKGROUND: Pediatric oncology patients with prolonged (≥96 hours) febrile neutropenia (absolute neutrophil count < 500/µL) often undergo an evaluation for invasive fungal disease (IFD) and other infections. Current literature suggests that beta-D-glucan (BDG), galactomannan, bronchoalveolar lavage (BAL), and computed tomography (CT) scans (sinus, chest, and abdomen/pelvis) may help determine a diagnosis in this population. METHODS: In a retrospective cohort study of all cancer/stem cell transplant patients (diagnosed 2005-2019) from one pediatric hospital, all episodes with prolonged febrile neutropenia or IFD evaluations (defined as sending a fungal biomarker or performing a CT scan to assess for infection) were identified. RESULTS: In total, 503 episodes met inclusion criteria and 64% underwent IFD evaluations. In total, 36.4% of episodes documented an infection after initiation of prolonged febrile evaluation, most commonly Clostridioides difficile colitis (6.4%) followed by a true bacterial bloodstream infection (BSI) (5.2%), proven/probable IFD (4.8%), and positive respiratory pathogen panel (3.6%). There was no difference in sinus CTs showing sinusitis (74% vs 63%, p = 0.46), whereas 32% of abdomen/pelvis CTs led to a non-IFD diagnosis, and 25% of chest CTs showed possible pneumonia. On chest CT, the positive predictive value (PPV) for IFD was 19% for nodules and 14% for tree and bud lesions. BDG had a PPV of 25% for IFD and GM 50%. BAL diagnosed IFD once and pneumocystis jirovecii pneumonia twice. CONCLUSIONS: Chest CTs and abdomen/pelvis CTs provide clinically relevant information during the prolonged febrile neutropenia evaluation, whereas BDG, galactomannan, BAL, and sinus CTs have less certain utility.

Priorities and Progress in Diagnostic Research by the Antibacterial Resistance Leadership Group.

The advancement of infectious disease diagnostics, along with studies devoted to infections caused by gram-negative and gram-positive bacteria, is a top scientific priority of the Antibacterial Resistance Leadership Group (ARLG). Diagnostic tests for infectious diseases are rapidly evolving and improving. However, the availability of rapid tests designed to determine antibacterial resistance or susceptibility directly in clinical specimens remains limited, especially for gram-negative organisms. Additionally, the clinical impact of many new tests, including an understanding of how best to use them to inform optimal antibiotic prescribing, remains to be defined. This review summarizes the recent work of the ARLG toward addressing these unmet needs in the diagnostics field and describes future directions for clinical research aimed at curbing the threat of antibiotic-resistant bacterial infections.

Multidrug-Resistant Bacterial Infections Among Very Low Birthweight Infants With Late-Onset Sepsis in Johannesburg, South Africa.

Background: An estimated 2.4 million babies died within the first 28 days of life in 2020. The third leading cause of neonatal death continues to be neonatal sepsis. Sepsis-causing bacterial pathogens vary temporally and geographically and, with a rise in multidrug-resistant organisms (MDROs), pose a threat to the neonatal population. Methods: This was a single-center, retrospective study of very low birth weight (VLBW) infants with late-onset sepsis (LOS) admitted to a neonatal unit in South Africa. We aimed to calculate the prevalence of multidrug-resistant (MDR) infections in this population. The data collected included demographic and clinical characteristics, length of hospital stay, risk factors for MDRO and mortality, and microbiology results. Logistic regression was used to assess the association between prespecified risk factors with MDR infections and mortality. Results: Of 2570 VLBW infants admitted, 34% had LOS, of which 33% was caused by MDROs. Infection with Acinetobacter spp., Pseudomonas spp., extended-spectrum beta-lactamase Klebsiella spp., or Escherichia coli was associated with the highest mortality in the LOS cohort. Infants with congenital infections (adjusted odds ratio [aOR], 5.13; 95% CI, 1.19-22.02; P = .028) or a history of necrotizing enterocolitis (aOR, 2.17; 95% CI, 1.05-4.49; P = .037) were at significantly higher risk for MDR infections. Conclusions: More than one-third of LOS cases in VLBW infants were caused by MDROs in this study. MDR infections cause substantial neonatal mortality. Antimicrobial stewardship programs, infection control protocols, and ongoing surveillance are needed to prevent further emergence and spread of MDR infections worldwide.

Re-emergence of Parechovirus: 2017-2022 National Trends of Detection in Cerebrospinal Fluid.

Increasing parechovirus (PeV) infections prompted a Centers for Disease Control and Prevention Health Advisory in July 2022. We retrospectively assessed national PeV trends in cerebrospinal fluid and observed unexpected viral dynamics from 2020 to 2022 with regional variance. These findings may be due to mitigation strategies aimed at severe acute respiratory syndrome coronavirus 2. PeV testing can benefit ill patients, particularly children.

Applying a risk prediction model for bloodstream infection in a febrile, nonseverely neutropenic cohort of pediatric stem cell transplant patients.

BACKGROUND: The optimal management of febrile stem cell transplant (SCT) patients presenting without severe neutropenia (absolute neutrophil count [ANC] ≥ 500/µL) is unclear. The authors have developed iterative risk prediction models (Esbenshade Vanderbilt [EsVan] models) that reliably predict bloodstream infections (BSIs) in the febrile general pediatric oncology population without severe neutropenia, but SCT-specific data are limited. METHODS: All SCTs occurring from May 2005 to November 2019 at a single institution were identified. Episodes of fever with a central venous catheter and ANC values ≥ 500/µL were abstracted. All previous versions of the EsVan model were applied to the SCT data, and c-statistics were generated. The models were additionally applied to each type of transplant (autologous/allogeneic), and a new allogeneic model that further adjusted for metrics of immunosuppression, Esbenshade Vanderbilt Allogeneic SCT Model (EsVanAlloSCT), was developed and internally validated. RESULTS: For 429 SCT episodes (221 autologous and 208 allogeneic), the BSI incidence was 19.6% (84 of 429), and it was higher in allogeneic transplant patients (25.5%) than autologous transplant patients (14.0%; p < .01). All versions of the EsVan model performed well for the overall SCT cohort (c-statistics, 0.759-0.795). The EsVan models performed better for the autologous episodes (c-statistics, 0.869-0.881) than the allogeneic SCT episodes (c-statistics, 0.678-0.717). The new allogeneic transplant-specific model, EsVanAlloSCT, which added an adjustment for the extent of immunosuppression, yielded a c-statistic of 0.792 (bootstrap-corrected, 0.750). CONCLUSIONS: The EsVan models work exceptionally well when they are applied to autologous SCT, but they work less well for allogeneic SCT. EsVanAlloSCT appears to improve the predictive ability in allogeneic SCT, but it will need additional external validation.

Antibiotic perceptions, adherence, and disposal practices among parents of pediatric patients.

Antibiotics are frequently prescribed for children in the outpatient setting. Although sometimes necessary, antibiotic use is associated with important downstream effects including the development of antimicrobial resistance among human and environmental microorganisms. Current outpatient stewardship efforts focus on guiding appropriate antibiotic prescribing practices among providers, but little is known about parents' understanding of antibiotics and appropriate disposal of leftover antibiotics. To help bridge this gap, we conducted a qualitative study to assess parental understanding of their children's antibiotics, their adherence to antibiotic instructions, and their disposal practices. We conducted a semi-structured interview with parents of 13 children diagnosed with acute respiratory illnesses and prescribed antibiotics in an urban outpatient clinic. We found that parents had limited understanding of how antibiotics work. Although they received instructions about antibiotic use during the healthcare visit, adherence to the prescription and appropriate disposal of antibiotics was suboptimal. Limited baseline understanding of antibiotics, their prior experiences with antibiotics, perceptions about their social networks' antibiotic use, and information provided to them by healthcare providers may influence these behaviors. Our findings can inform educational efforts of outpatient stewardship programs to help optimize parental understanding of how to use and dispose of their children's antibiotics.

Molecular diagnostics for genotypic detection of antibiotic resistance: current landscape and future directions.

Antimicrobial resistance (AMR) among bacteria is an escalating public health emergency that has worsened during the COVID-19 pandemic. When making antibiotic treatment decisions, clinicians rely heavily on determination of antibiotic susceptibility or resistance by the microbiology laboratory, but conventional methods often take several days to identify AMR. There are now several commercially available molecular methods that detect antibiotic resistance genes within hours rather than days. While these methods have limitations, they offer promise for optimizing treatment and patient outcomes, and reducing further emergence of AMR. This review provides an overview of commercially available genotypic assays that detect individual resistance genes and/or resistance-associated mutations in a variety of specimen types and discusses how clinical outcomes studies may be used to demonstrate clinical utility of such diagnostics.

Serious infections are rare in well-appearing neonates with hypothermia identified incidentally at routine visits.

OBJECTIVES: It is not established whether diagnostic testing and antimicrobial treatment are warranted in well-appearing neonates without other signs or symptoms who have hypothermia identified incidentally at a routine visit with their primary care provider. METHODS: This was a retrospective observational study of well-appearing neonates who were noted at a routine visit to be hypothermic (<97.7°F or <36.5°C) and referred to a pediatric emergency department over an 8.5-year period. Excluded were those transferred from an outside hospital and those with signs of illness, including apnea, bradycardia, fever, hypoglycemia, ill appearance, lethargy, poor feeding, respiratory distress, tachycardia, or vomiting. Patient characteristics, laboratory results, antimicrobial treatment, and clinical outcomes were recorded. RESULTS: Among a final cohort of 212 neonates with incidental hypothermia, no urine (n = 195) or blood (n = 198) culture grew a bacterial pathogen. No CSF culture (n = 168) grew a bacterial pathogen and no CSF PCR test (n = 142) was positive for herpes simplex virus. Contaminants were isolated in 3 urine and 3 blood cultures. CONCLUSION: Well-appearing neonates with incidentally noted hypothermia at a routine visit are at low risk for serious infection and may not warrant a full sepsis evaluation.

A qualitative assessment of nonclinical drivers of pediatric outpatient antibiotic prescribing: The importance of continuity.

Background and objectives: Antibiotic overuse is common in outpatient pediatrics and varies across clinical setting and clinician type. We sought to identify social, behavioral, and environmental drivers of outpatient antibiotic prescribing for pediatric patients. Methods: We conducted semistructured interviews with physicians and advanced practice providers (APPs) across diverse outpatient settings including pediatric primary, urgent, and retail care. We used the grounded theory constant comparative method and a thematic approach to analysis. We developed a conceptual model, building on domains of continuity to map common themes and their relationships within the healthcare system. Results: We interviewed 55 physicians and APPs. Clinicians across all settings prioritized provision of guideline-concordant care but implemented these guidelines with varying degrees of success. The provision of guideline-concordant care was influenced by the patient-clinician relationship and patient or parent expectations (relational continuity); the clinician's access to patient clinical history (informational continuity); and the consistency of care delivered (management continuity). No difference in described themes was determined by setting or clinician type; however, clinicians in primary care described having more reliable relational and informational continuity. Conclusions: Clinicians described the absence of long-term relationships (relational continuity) and lack of availability of prior clinical history (informational continuity) as factors that may influence outpatient antibiotic prescribing. Guideline-concordant outpatient antibiotic prescribing was facilitated by consistent practice across settings (management continuity) and the presence of relational and informational continuity, which are common only in primary care. Management continuity may be more modifiable than informational and relational continuity and thus a focus for outpatient stewardship programs.

Improvements in appropriate ambulatory antibiotic prescribing using a bundled antibiotic stewardship intervention in general pediatrics practices.

OBJECTIVE: To improve appropriate antibiotic prescribing for children in Tennessee. DESIGN: We performed a before-and-after intervention study with 3 comparison periods: period 1 (P1, baseline) May 2018-September 2019; period 2 (P2, intervention before the COVID-19 pandemic) November 11, 2019-March 20, 2020; and period 3 (P3, intervention during the coronavirus disease 2019 [COVID-19] pandemic) March 21, 2020-November 10, 2020. We additionally surveyed participating providers to assess acceptance of the intervention. SETTING: Community general pediatrics practices. PARTICIPANTS: In total, 81 general pediatricians, family medicine physicians, and nurse practitioners in 5 general pediatrics practices participated in this study. INTERVENTIONS: Each practice identified a practice and operations champion for the project. Practices chose 2-4 implementation strategies previously shown to be effective at reducing outpatient antibiotic use to implement in their practice throughout the study intervention period. Study personnel also held quarterly meetings with all providers to review deidentified peer comparison feedback both across practices enrolled in the study and at the provider level within each practice. RESULTS: We detected improvements in guideline-concordant antibiotic use in the pre-COVID-19 intervention period, and they were sustained in the study period during the pandemic (P3): otitis media (P1 72.14% vs P2 81.42% vs P3 86.11%), group A streptococcal pharyngitis (P1 66.13% vs P2 81.56% vs P3 80.44%), pneumonia (P1 70.6% vs P2 76.2% vs P3 100%), sinusitis (P1 76.2% vs P2 83.78% vs P3 82.86%), skin and soft-tissue infections (P1 97.18% vs P2 100% vs P3 100%). CONCLUSIONS: Bundled implementation strategies led to significant increases in guideline-concordant antibiotic prescribing for all diagnoses. Survey results demonstrate that the bundled implementation strategies were well-accepted by providers.

Accuracy of a Rapid Multiplex Polymerase Chain Reaction Plus a Chromogenic Phenotypic Test Algorithm for Detection of Extended-Spectrum ß-Lactamase and Carbapenemase-Producing Gram-Negative Bacilli in Positive Blood Culture Bottles.

We studied the performance of an algorithm combining multiplex polymerase chain reaction with phenotypic detection of extended-spectrum ß-lactamases and carbapenemases directly from positive blood culture bottles in patients with gram-negative bacteremia and found good concordance with routine cultures. Such an algorithm may be a tool to improve time to optimal therapy in patients with gram-negative bacteremia.

Variation in antibiotic use among neonatal intensive care units in the United States.

Antibiotics are widely used in neonatal intensive care units (NICUs). We conducted a cross-sectional analysis of antibiotic use across US NICUs to evaluate overall, broad-spectrum, and combination antibiotic use. Patterns of antibiotic use varied by medical versus surgical service line, hospital, and geographic location.