Disseminated Nocardia nova in a child with relapsed acute lymphoblastic leukemia: a case report.

BACKGROUND: Nocardiosis is a rare infection that typically results from inhalation of or inoculation with Nocardia organisms. It may cause invasive disease in immunocompromised patients. This case describes nocardiosis with bacteremia and pulmonary involvement in a child with a hematologic malignancy. CASE PRESENTATION: A boy with testicular relapsed acute lymphoblastic leukemia with marrow involvement presented with sudden onset of fever, body aches, headaches, chills, and moderate respiratory distress during continuation 2 chemotherapy. Radiographic imaging demonstrated consolidation and ground glass opacities in bilateral lower lungs. Central line blood cultures grew Nocardia nova complex, prompting removal of the central line and initiation of triple therapy with imipenem-cilastatin, linezolid, and trimethoprim-sulfamethoxazole with rapid improvement of symptoms. Antibiotic susceptibilities showed a multidrug-susceptible isolate. The patient is anticipated to remain on trimethoprim-sulfamethoxazole for at least 12 months. CONCLUSIONS: In an immunocompromised child, blood cultures, chest imaging, and head imaging can aid in the diagnosis of disseminated nocardiosis. Long-term antibiotic therapy is necessary, guided by the organism and simplified with the results of antimicrobial susceptibility testing.

Multi-institutional experience with COVID-19 convalescent plasma in children.

BACKGROUND AND OBJECTIVES: Convalescent COVID-19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high-titer CCP early in the disease course of patients who are expected to be antibody-negative; however, pediatric experience is limited. We created a multi-institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention. METHODS: A REDCap survey was distributed. The registry collected de-identified data including demographic information (age, gender, and underlying conditions), COVID-19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response. RESULTS: Ninety-five children received CCP: 90 inpatients and 5 outpatients, with a median age of 10.2 years (range 0-17.9). They were predominantly Latino/Hispanic and White. The most frequent underlying medical conditions were chronic respiratory disease, immunosuppression, obesity, and genetic syndromes. CCP was primarily given as a treatment (95%) rather than prophylaxis (5%). Median total plasma dose administered and transfusion rates were 5.0 ml/kg and 2.6 ml/kg/h, respectively. The transfusions were well-tolerated, with 3 in 115 transfusions reporting mild reactions. No serious adverse events were reported. Severity scores decreased significantly 7 days after CCP transfusion or at discharge. Eighty-five patients (94.4%) survived to hospital discharge. All five outpatients survived to 60 days. CONCLUSIONS: CCP was found to be safe and well-tolerated in children. CCP was frequently given concurrently with other COVID-19-directed treatments with improvement in clinical severity scores ≥7 days after CCP, but efficacy could not be evaluated in this study.

Standardizing Strep Throat Documentation in a Pediatric Outpatient Setting During COVID-19: A Quality Improvement Pilot Project.

Clinicians' nonadherence to the 2012 Infectious Diseases Society of America's group A streptococcal (GAS) pharyngitis guidelines leads to unnecessary in-person clinic visits, unnecessary use of bacterial testing, and inappropriate antibiotic prescriptions. Quality improvement methodology was used during nurse telephone triage at an outpatient pediatric clinic to standardize nurse documentation to align with the GAS guidelines. This pilot project's standardization resulted in improved communication among clinicians and decreased unnecessary resource and antibiotic use despite encountering barriers related to COVID-19.

Evaluation of the Infectious Diseases Society of America's Core Antimicrobial Stewardship Curriculum for Infectious Diseases Fellows.

BACKGROUND: Antimicrobial stewardship (AS) programs are required by Centers for Medicare and Medicaid Services and should ideally have infectious diseases (ID) physician involvement; however, only 50% of ID fellowship programs have formal AS curricula. The Infectious Diseases Society of America (IDSA) formed a workgroup to develop a core AS curriculum for ID fellows. Here we study its impact. METHODS: ID program directors and fellows in 56 fellowship programs were surveyed regarding the content and effectiveness of their AS training before and after implementation of the IDSA curriculum. Fellows' knowledge was assessed using multiple-choice questions. Fellows completing their first year of fellowship were surveyed before curriculum implementation ("pre-curriculum") and compared to first-year fellows who complete the curriculum the following year ("post-curriculum"). RESULTS: Forty-nine (88%) program directors and 105 (67%) fellows completed the pre-curriculum surveys; 35 (64%) program directors and 79 (50%) fellows completed the post-curriculum surveys. Prior to IDSA curriculum implementation, only 51% of programs had a "formal" curriculum. After implementation, satisfaction with AS training increased among program directors (16% to 68%) and fellows (51% to 68%). Fellows' confidence increased in 7/10 AS content areas. Knowledge scores improved from a mean of 4.6 to 5.1 correct answers of 9 questions (P = .028). The major hurdle to curriculum implementation was time, both for formal teaching and for e-learning. CONCLUSIONS: Effective AS training is a critical component of ID fellowship training. The IDSA Core AS Curriculum can enhance AS training, increase fellow confidence, and improve overall satisfaction of fellows and program directors.

Antibiotics prior to age 2 years have limited association with preschool growth trajectory.

BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.

Investing in the Future: A Role for Professional Societies to Prepare the Next Generation of Healthcare Leaders Through Curriculum Development and Dissemination.

Professional societies serve many functions that benefit constituents; however, few professional societies have undertaken the development and dissemination of formal, national curricula to train the future workforce while simultaneously addressing significant healthcare needs. The Infectious Diseases Society of America (IDSA) has developed 2 curricula for the specific purpose of training the next generation of clinicians to ensure the future infectious diseases (ID) workforce is optimally trained to lead antimicrobial stewardship programs and equipped to meet the challenges of multidrug resistance, patient safety, and healthcare quality improvement. A core curriculum was developed to provide a foundation in antimicrobial stewardship for all ID fellows, regardless of career path. An advanced curriculum was developed for ID fellows specifically pursuing a career in antimicrobial stewardship. Both curricula will be broadly available in the summer of 2021 through the IDSA website.

Strategies to improve antibiotic use in the neonatal ICU.

PURPOSE OF REVIEW: Neonates are at a high risk of infection and may have nonspecific signs of sepsis. Accordingly, they are heavily exposed to antimicrobials. Neonates are also uniquely at risk of both short-term and long-term complications from antibiotic exposure. This review discusses advances in antibiotic stewardship in the neonatal population. RECENT FINDINGS: Antimicrobial utilization is highly variable among NICUs in excess of case-mix variation. Rates of early-onset sepsis because of Group B Streptococcus have decreased substantially with the introduction of intrapartum antibiotic prophylaxis. Recent epidemiologic studies have created evidence-based tools to more accurately estimate a newborn's risk of early-onset sepsis. Antibiotic selection and duration for late-onset sepsis and necrotizing enterocolitis are variable among centers, with inadequate evidence to guide practice. Novel diagnostic methods and biomarkers are increasingly used to assist with diagnosing infection, but inadequate specificity in many cases may result in excess antibiotic exposure. Published antimicrobial stewardship experiences in the neonatal inpatient setting have largely been successful and well tolerated. SUMMARY: Recent publications have identified many ways to safely reduce antimicrobial exposure and developed strategies to implement antimicrobial stewardship in the neonatal inpatient setting. However, new approaches are needed to further improve antibiotic use and to implement these interventions more universally in NICUs.

Intensity of Therapy for Malignancy and Risk for Recurrent and Complicated Clostridium difficile Infection in Children.

Clostridium difficile infection (CDI) is common in pediatric oncology patients and is often associated with recurrences and complications. We hypothesized that higher intensity of chemotherapy would be associated with these outcomes. We conducted a retrospective cohort study including all cases of primary CDI in children with malignancy in our institution for over 7 years. Intensity of chemotherapy was measured by the Intensity of Treatment Rating Scale, third edition, ranging from level 1 (minimal) to 4 (highest). Outcomes included recurrence within both 56 and 180 days, CDI-associated complications, and primary treatment failure (PTF). Risk of recurrence was compared using Cox proportional hazards regression. Among 192 patients with CDI and malignancy, 122 met inclusion criteria. CDI recurred in 27% (31/115) of patients followed for 56 days and 46% (48/104) of patients followed for 180 days. Fourteen patients (11.4%) had a CDI-associated complication, including 4 intensive care unit admissions and 3 surgical procedures, but no deaths. Ten patients (8.2%) had PTF. Although PTF and severe complications were infrequent, recurrence was common in our cohort. None of these outcomes were associated with level of treatment intensity. More research is required to assess oncologic and nononcologic risk factors for CDI recurrence, PTF, and severe CDI-associated complications.

Measuring the Value of a Clinical Practice Guideline for Children With Perforated Appendicitis.

OBJECTIVE: To determine the incremental cost-effectiveness of a clinical practice guideline (CPG) compared with "usual care" for treatment of perforated appendicitis in children. Secondary objective was to compare cost analyses using hospital accounting system data versus data in the Pediatric Health Information System (PHIS). BACKGROUND: Value-based surgical care (outcomes relative to costs) is frequently touted, but outcomes and costs are rarely measured together. METHODS: During an 18-month period, 122 children with perforated appendicitis at a tertiary referral children's hospital were treated using an evidence-based CPG. Clinical outcomes and costs for the CPG cohort were compared with patients in the 30-month period before CPG implementation (n = 191 children). RESULTS: With CPG-directed care, intra-abdominal abscess rate decreased from 0.24 to 0.10 (adjusted risk ratio 0.44, 95% confidence interval [CI] 0.26-0.75). The rate of any adverse event decreased from 0.30 to 0.23 (adjusted risk ratio 0.82, 95% CI 0.58-1.17). Mean total hospital costs per patient (hospital accounting system) decreased from $16,466 to $10,528 (adjusted absolute difference-$5451, 95% CI -$7755 to -$3147), leading to estimated adjusted total savings of $665,022 during the study period. Costs obtained from the PHIS database also showed reduction with CPG-directed care (-$6669, 95% CI -$8949 to -$4389 per patient). In Bayesian cost-effectiveness analyses, likelihood that CPG was the dominant strategy was 91%. CONCLUSIONS: An evidence-based CPG increased the value of surgical care for children with perforated appendicitis by improving outcomes and lowering costs. Hospital cost accounting data and pre-existing cost data within the PHIS database provided similar results.

Risk Factors for Pediatric Critical COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Risk stratification is a cornerstone of the Pediatric Infectious Diseases Society COVID-19 treatment guidance. This systematic review and meta-analysis aimed to define the clinical characteristics and comorbidities associated with critical COVID-19 in children and adolescents. METHODS: Two independent reviewers screened the literature (Medline and EMBASE) for studies published through August 31, 2023, that reported outcome data on patients aged ≤21 years with COVID-19. Critical disease was defined as an invasive mechanical ventilation requirement, intensive care unit admission, or death. Random-effects models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was explored through subgroup analyses. RESULTS: Among 10,178 articles, 136 studies met the inclusion criteria for review. Data from 70 studies, which collectively examined 172,165 children and adolescents with COVID-19, were pooled for meta-analysis. In previously healthy children, the absolute risk of critical disease from COVID-19 was 4% (95% CI, 1%-10%). Compared with no comorbidities, the pooled OR for critical disease was 3.95 (95% CI, 2.78-5.63) for the presence of one comorbidity and 9.51 (95% CI, 5.62-16.06) for ≥2 comorbidities. Key risk factors included cardiovascular and neurological disorders, chronic pulmonary conditions (excluding asthma), diabetes, obesity, and immunocompromise, all with statistically significant ORs > 2.00. CONCLUSIONS: While the absolute risk for critical COVID-19 in children and adolescents without underlying health conditions is relatively low, the presence of one or more comorbidities was associated with markedly increased risk. These findings support the importance of risk stratification in tailoring pediatric COVID-19 management.

Risk Factors for Pediatric Critical COVID-19: A Systematic Review and Meta-Analysis.

Background: Risk stratification is a cornerstone of the Pediatric Infectious Diseases Society COVID-19 treatment guidance. This systematic review and meta-analysis aimed to define the clinical characteristics and comorbidities associated with critical COVID-19 in children and adolescents. Methods: Two independent reviewers screened the literature (Medline and EMBASE) for studies published through August 2023 that reported outcome data on patients aged ≤21 years with COVID-19. Critical disease was defined as an invasive mechanical ventilation requirement, intensive care unit admission, or death. Random effects models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was explored through subgroup analyses. Results: Among 10,178 articles, 136 studies met the inclusion criteria for review. Data from 70 studies, which collectively examined 172,165 children and adolescents with COVID-19, were pooled for meta-analysis. In previously healthy children, the absolute risk of critical disease from COVID-19 was 4% (95% CI, 1%-10%). Compared with no comorbidities, the pooled OR for critical disease was 3.95 (95% CI, 2.78-5.63) for presence of one comorbidity and 9.51 (95% CI, 5.62-16.06) for ≥2 comorbidities. Key risk factors included cardiovascular and neurological disorders, chronic pulmonary conditions (excluding asthma), diabetes, obesity, and immunocompromise, all with statistically significant ORs >2.00. Conclusions: While the absolute risk for critical COVID-19 in children and adolescents without underlying health conditions is relatively low, the presence of one or more comorbidities was associated with markedly increased risk. These findings support the importance of risk stratification in tailoring pediatric COVID-19 management.

Guidance for prevention and management of COVID-19 in children and adolescents: A consensus statement from the Pediatric Infectious Diseases Society Pediatric COVID-19 Therapies Taskforce.

BACKGROUND: Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. RESULTS: There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.

Monoclonal Antibodies for COVID-19 in Children: Case Series Should be Just the Start.

Two new articles describe the use and implementation of monoclonal antibodies to treat COVID-19 in children. While these studies provide valuable guidance for pediatric clinicians, more studies of monoclonal antibodies and other COVID-19 therapies in children are needed.

Severe multiple organ failure as a consequence of diabetic ketoacidosis in an adolescent with new-onset type 1 diabetes: A case report.

The initial presentation of pediatric diabetes is variable, making prompt diagnosis and treatment challenging. The overlap between type 1 and type 2 diabetes and presence of developmental delays can complicate diagnosis, resulting in delays and severe illness at presentation. Here we describe a case of a 13-year-old male with autism and attention deficit hyperactivity disorder who presented with severe diabetic ketoacidosis, multiple organ failure, and shock. Within 2 weeks of this initial presentation, he had further clinical decompensation due to an intestinal perforation. Cultures from resected gastrointestinal tissue grew mucormycosis, protracting his hospital stay and recovery. He was able to go home several months later with remarkable improvement. This case highlights the necessity of careful history taking and early testing, and how investigation for rare complications of diabetes is vital when patients do not improve as expected.

Early antibiotic exposure in very-low birth weight infants and infection risk at 3-7 days after birth.

OBJECTIVE: To determine rates of late-onset infection (LOI) during postnatal days 3-7 among preterm infants, based on antibiotic exposure during days 0-2. STUDY DESIGN: Retrospective cohort study of infants born <1500 grams and ≤30 weeks gestation, 2005-2018. We analyzed the incidence and microbiology of LOI at days 3-7 based on antibiotic exposure during postnatal days 0-2. RESULTS: The cohort included 88,574 infants, of whom 85% were antibiotic-exposed. Fewer antibiotic-exposed compared to unexposed infants developed LOI (1.5% vs. 2.1%; adjusted hazard ratio, 0.28, 95% CI 0.24-0.33). Among antibiotic-exposed compared to unexposed infants, Gram-negative (38% vs. 28%, p = 0.002) and fungal (11% vs. 1%, p < 0.001) species were more commonly isolated, and gram-positive organisms (49% vs. 70%, p < 0.001) were less commonly isolated. CONCLUSIONS: We observed low overall rates of LOI at days 3-7 after birth, but antibiotic exposure from birth was associated with lower rates, and with differing microbiology, compared to no exposure.

Benchmarking of Outpatient Pediatric Antibiotic Prescribing: Results of a Multicenter Collaborative.

BACKGROUND: Most antibiotic use occurs in ambulatory settings. No benchmarks exist for pediatric institutions to assess their outpatient antibiotic use and compare prescribing rates to peers. We aimed to share pediatric outpatient antibiotic use reports and benchmarking metrics nationally. METHODS: We invited institutions from the Sharing Antimicrobial Reports for Pediatric Stewardship OutPatient (SHARPS-OP) Collaborative to contribute quarterly aggregate reports on antibiotic use from January 2019 to June 2022. Outpatient settings included emergency departments (ED), urgent care centers (UCC), primary care clinics (PCC) and telehealth encounters. Benchmarking metrics included the percentage of: (1) all acute encounters resulting in antibiotic prescriptions; (2) acute respiratory infection (ARI) encounters resulting in antibiotic prescriptions; and among ARI encounters receiving antibiotics, (3) the percentage receiving amoxicillin ("Amoxicillin index"); and (4) the percentage receiving azithromycin ("Azithromycin index"). We collected rates of antibiotic prescriptions with durations ≤7 days and >10 days from institutions able to provide validated duration data. RESULTS: Twenty-one institutions submitted aggregate reports. Percent ARI encounters receiving antibiotics were highest in the UCC (40.2%), and lowest in telehealth (19.1%). Amoxicillin index was highest for the ED (76.2%), and lowest for telehealth (55.8%), while the azithromycin index was similar for ED, UCC, and PCC (3.8%, 3.7%, and 5.0% respectively). Antibiotic duration of ≤7 days varied substantially (46.4% for ED, 27.8% UCC, 23.7% telehealth, and 16.4% PCC). CONCLUSIONS: We developed a benchmarking platform for key pediatric outpatient antibiotic use metrics drawing data from multiple pediatric institutions nationally. These data may serve as a baseline measurement for future improvement work.

Implementation of Electronic Clinical Decision Support Tools for Antibiotic Stewardship in Pediatric Appendicitis.

BACKGROUND: The efficacy of clinical decision support (CDS) tools to promote antibiotic stewardship in pediatric appendicitis remains poorly understood. Here, we developed an electronic order panel (OP) to assist with decreased utilization of extended spectrum antibiotics. METHODS: Retrospective review of patients (≤18 years) at a single institution from May 2018 to October 2019 treated with ≥1 dose of preferred (narrow) or nonpreferred (broad-spectrum) antibiotics was performed, and they were categorized as pre- (PIC) or postimplementation cohorts (PISC). RESULTS: Of 234 encounters, 170 (73%) and 107 (46%) received preferred and nonpreferred antibiotics, respectively. Postimplementation cohort encounters had a sustained 50% increase in preferred antibiotic use compared to PIC (92% vs 42%, P = .014). Order panel utilization accounted for 31% of overall encounters and 44% of PISC encounters. CONCLUSION: Despite sustained improvement in antibiotic stewardship, OP utilization remains low. The use of CDS tools may not be a good process measure for quality improvement.

Pediatric antimicrobial stewardship practices at discharge: A national survey.

We surveyed pediatric antimicrobial stewardship program (ASP) site leaders within the Sharing Antimicrobial Reports for Pediatric Stewardship collaborative regarding discharge stewardship practices. Among 67 sites, 13 (19%) reported ASP review of discharge antimicrobial prescriptions. These findings highlight discharge stewardship as a potential opportunity for improvement during the hospital-to-home transition.