Use of Continuous Ketamine Infusion as an Adjunctive Agent in Young Infants With Refractory and Super Refractory Status Epilepticus: A Case Series.

Continuous ketamine infusions have been studied as an adjunctive agent for refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) in older children and adults. However, minimal information exists on the efficacy, safety, and dosing for continuous ketamine in young infants. We present the clinical course of 3 young infants with RSE and SRSE who received continuous ketamine in conjunction with other antiseizure medications. The condition of these patients was refractory to an average of 6 antiseizure medications before initiation of continuous ketamine infusion. For each patient, a continuous ketamine infusion was initiated at a rate of 1 mg/kg/hr with 1 patient requiring titration to a maximum of 6 mg/kg/hr. In 1 case, the concomitant use of continuous ketamine allowed for a reduction in the benzodiazepine continuous infusion rate. In all cases, ketamine was well tolerated especially in the setting of hemodynamic instability. Ketamine may provide a safe adjunct in the acute setting in severe RSE and SRSE. This is the first case series to document the use of continuous ketamine as a treatment modality in young infants with RSE or SRSE secondary to various underlying etiologies, without adverse events. Further studies are needed to evaluate the long-term safety and efficacy of continuous ketamine in this patient population.

Risk Factors for Venous Thromboembolic Events in Children With Acute Musculoskeletal Infections.

BACKGROUND AND OBJECTIVES: Venous thromboembolic events (VTE) complicate acute hematogenous musculoskeletal infections (MSKIs) among hospitalized children. However, there is limited guidance for which specific MSKI patients are at the greatest VTE risk. This study aimed to identify VTE risk factors for children hospitalized with MSKIs. METHODS: A retrospective chart review was performed of children hospitalized with MSKIs at a single quaternary care pediatric hospital during a 9-year period. Patients with chronic MSKIs, non-hematogenous infections, or significant contributing comorbidities were excluded. Demographic and clinical characteristics were compared between patients with and without VTE using forward stepwise conditional multivariable logistic regression to identify VTE risk factors. RESULTS: Among 335 included patients, 7 (2.1%) developed a VTE. There was no difference in age, sex, or obesity rates for those with or without VTE. Patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and/or critical illness were more likely to develop a VTE with summative adjusted odds ratios of 31.7 and 26.4, respectively. In addition, patients with VTEs had longer hospitalizations (median 4.7 vs. 12.8 d, P <0.001), longer courses of intravenous antimicrobials (median 3.7 vs. 13.5 d, P =0.001), and longer time to fever resolution (median 25.7 vs. 162 h, P =0.004). CONCLUSIONS: VTE prevalence among children with acute MSKIs is low. MRSA infection and critical illness significantly increase the risk for VTE development in these patients. Future prospective studies are needed to determine if VTEs in high-risk MSKI patients can be prevented.

Microbiology Culture Results and Antibiotic Prescribing in Pediatric Patients With Lymphadenitis.

BACKGROUND: Bacterial lymphadenitis is a common reason for antibiotic treatment and hospitalization in children. The literature available addressing the bacterial etiology of lymphadenitis recommends the use of narrow-spectrum agents to cover common pathogens. We suspect that patients at our institution receive unnecessarily broad-spectrum antimicrobial agents. The primary objective of this study was to characterize the microbiology and antibiotic use in lymphadenitis patients. METHODS: Retrospective review of children admitted over a 10-year period with an International Classification of Diseases Ninth or Tenth Edition code for lymphadenitis. Patients were included if they were <18 years old, admitted to the inpatient ward, and had intraoperative lymph node cultures collected. RESULTS: A total of 131 patients admitted with lymphadenitis had lymph node cultures collected and were included. Seventy-two (72/131; 55%) patients had positive lymph node culture results with pathogenic bacteria. The predominant pathogens were Staphylococcus aureus (56/72; 77.8%) and Streptococcus pyogenes (10/72; 13.9%). The most common inpatient empirical regimen was ampicillin-sulbactam. Of the 72 patients with typical pathogens identified, 80.6% were sensitive to a first-generation cephalosporin, whereas 86.1% were sensitive to a ß-lactam/ß-lactamase inhibitor. CONCLUSION: Patients presenting to our institution with acute bacterial lymphadenitis were predominantly found to have methicillin-susceptible S. aureus lymphadenitis that could be empirically treated with cefazolin. At our institution, there is little advantage to the most commonly used broad-spectrum agent, ampicillin-sulbactam.

Identifying predictors for source culture positivity in children with acute musculoskeletal infections.

OBJECTIVES: Identifying the causative bacterial pathogen for children with acute hematogenous musculoskeletal infections (MSKIs) allows for improved care. The purpose of our study was to determine if clinical markers could predict which patients will have a causative pathogen found on source culture alone, thus being highest yield to undergo operative diagnostic procedures. METHODS: A single-center, retrospective cohort study was performed. Medical records for patients between 6 months and 18 years of age admitted between July 2014 and September 2018 with a discharge diagnosis of acute osteomyelitis, septic arthritis, or pyomyositis were reviewed. Patients were stratified based on results of blood and source cultures. Predictors of interest were screened on a univariable basis with significant predictors retained in a multivariate analysis. RESULTS: There were 170 patients included. No predictors were significantly associated with increased odds of having a causative pathogen found on source culture alone. Degree of C-reactive protein elevation and history of fever were associated with decreased odds of being source culture positive, OR (95% CI); 0.92 (0.87, 0.98) and 0.39 (0.19, 0.81), respectively. CONCLUSIONS: Predictive modeling failed to identify children with MSKIs whose causative pathogen was found by source culture alone. It is difficult to predict which MSKI patients will be highest yield for operative diagnostic procedures.

Management of an Immunocompromised Pediatric Patient With Multiple Hospitalizations for Symptomatic COVID-19.

Relapse of infection due to SARS-CoV-2 has been rarely described and there is little guidance regarding the management of such cases in immunocompromised hosts. We present a case of an adolescent female with B-cell acute lymphoblastic leukemia hospitalized multiple times for symptomatic SARS-CoV-2 infection who was safely treated with 2 courses of remdesivir (RDV) and has had no additional readmissions to date. Though additional studies are needed to confirm the safety and efficacy of an additional course of RDV in the setting of relapsed or prolonged severe COVID-19, our observations suggest that a second course of RDV may be considered.

Pharmacological Management of Pediatric Clostridioides difficile Infection: Clarifying the Controversies.

Clostridioides difficile infection (CDI) is a major public health concern for pediatric and adult patients. The management of pediatric CDI poses a challenge to healthcare providers due to lack of strong randomized controlled trials to guide pharmacological management. Additionally, recent updates to CDI guidelines recommend oral vancomycin over metronidazole for the management of CDI in adults, leaving questions regarding how to best manage pediatric patients. This continuing education pharmacotherapy review describes available evidence for the safety and efficacy of medications used in the treatment and management of pediatric CDI and aims to clarify discrepancies between pediatric and adult recommendations.

Characteristics of Children With Culture Negative Acute Hematogenous Musculoskeletal Infections.

BACKGROUND: Identifying the causative pathogen for acute hematogenous musculoskeletal infections (MSKIs) allows for directed antimicrobial therapy and diagnostic confidence. However, 20% to 50% of children with acute MSKIs remain culture negative. The objective of this study was to compare characteristics of culture negative MSKI patients to those where a pathogen is identified. METHODS: Electronic medical records of children admitted between July 2014 to September 2018 to a single quaternary care pediatric hospital with acute MSKIs were retrospectively reviewed. Clinical and demographic characteristics were compared between culture positive and culture negative MSKIs. RESULTS: A total of 170 patients were included of whom 43 (25%) were culture negative. All culture negative patients had at least 1 culture type obtained, and the majority (84%) had both blood and source cultures performed. When compared with patients with a causative pathogen identified, culture negative patients were younger (2.3 vs. 9.8 y), smaller (13.5 vs. 31.6 kg), less likely to be febrile on arrival (56% vs. 77%), less likely to have an abscess on imaging (23% vs. 48%), and were more likely to have uncomplicated septic arthritis (35% vs. 8%). No critically ill patient was culture negative. Seven culture negative patients had additional Kingella kingae testing performed, none of which were positive. CONCLUSIONS: Despite targeted and standardized efforts to identify causative bacteria, 25% of children with acute MSKIs never have a pathogen identified. Culture negative patients are younger, less febrile, are less likely to have an abscess, and more likely to have isolated septic arthritis. LEVEL OF EVIDENCE: This is a retrospective cohort study interested in identifying patient characteristics that predict rate of culture positivity for acute MSKIs. This study meets criteria for Level II evidence.

Long-Term Impact of a Clinical Care Guideline for Pediatric Acute Musculoskeletal Infections: Are Improved Outcomes Sustainable?

BACKGROUND: Acute hematogenous musculoskeletal infections are a common cause of hospitalization in children. A locally developed clinical care guideline (CCG) for acute musculoskeletal infections was implemented at our quaternary care pediatric hospital in July 2012. The purpose of this study was to evaluate the long-term sustainability of previously described improvements after CCG implementation. METHODS: Clinical outcomes for children hospitalized with musculoskeletal infections at Children's Hospital Colorado from June 2009 through September 2018 were retrospectively reviewed. Patients were included if they had an International Classification of Diseases, Ninth Revision or International Classification of Diseases, 10th Revision discharge diagnosis of acute osteomyelitis, septic arthritis, or pyomyositis and were between 6 months and 18 years of age at admission. Patients with underlying medical complexity or nonhematogenous musculoskeletal infections were excluded. Patients were categorized by date of admission as either "pre-CCG" (June 2009 to June 2011) or "sustain-CCG" (July 2014 to September 2018). Primary outcomes were hospital length of stay and intravenous antimicrobial length of therapy. RESULTS: From pre-CCG to sustain-CCG, median length of stay decreased by 1.29 days (5.56 vs 4.27; P < .004) and median length of therapy decreased by 5.04 days (8.33 vs 3.29; P < .0001). Statistical process control charts support that these were sustained improvements many years after CCG implementation. Additional secondary clinical improvements were observed in the sustain-CCG group including faster fever resolution, more consistent blood and source culture acquisition, and decreased central line placement. There was no increase in related readmissions or therapeutic failures in the sustain-CCG group. CONCLUSIONS: Implementation of a CCG to standardize care for musculoskeletal infections can be sustained many years after implementation.