LOCALIZED MYOSITIS AND TRANSIENT ENCEPHALOPATHY AS PRESENTING SYMPTOMS IN MURINE TYPHUS.

Murine typhus in the pediatric population has increased substantially in recent years. The most common clinical presentation of murine typhus includes fever, rash, headaches and myalgias. Murine typhus presenting with predominant myositis and/or encephalopathy is rare. It is important to recognize unusual clinical manifestations of murine typhus in children for early diagnosis and treatment.

13-Year-Old Female With New Onset Multifocal Pulmonary Ground-Glass Opacities.

A 13-year-old female who recently emigrated from Honduras presented to an emergency department in Texas with a 2-month history of weight loss, fatigue, cough, and progressive shortness of breath. Her symptoms started with a nonproductive cough, and she later developed dyspnea on exertion and orthopnea. On physical examination, she was tachycardic and tachypneic. She had a thin, emaciated body habitus. She was visibly in respiratory distress with nasal flaring, tracheal tugging, and intercostal and subcostal retractions. She had diminished breath sounds at the bases and bibasilar crackles. A computed tomography scan of the chest revealed multifocal ground-glass opacities throughout all lobes of both lungs with small bilateral pleural effusions and prominent bilateral hilar lymph nodes. We will discuss the approach to the initial evaluation and subsequent diagnosis.

Management of Extensive Central Nervous System Cladophialophora bantiana Infection in a 9-Year-Old Child.

BACKGROUND: Pediatric central nervous system (CNS) phaeohyphomycosis is a rare invasive fungal infection associated with high mortality. METHODS: We describe a child with progressive neurologic symptoms whose ultimate diagnosis was Cladophialophora bantiana -associated CNS phaeohyphomycosis. We discuss her clinical presentation, medical and surgical management and review the current literature. RESULTS: A 9-year-old female presented with acute onset of headaches, ophthalmoplegia and ataxia. Initial infectious work-up was negative, including serial fungal cerebrospinal fluid cultures. Over 2 months, she experienced progressive cognitive and motor declines, and imaging revealed worsening meningitis, ventriculitis and cerebritis. Ultimately, Cladophialophora was detected by plasma metagenomic next-generation sequencing (mNGS). Fourth ventricle fluid sampling confirmed the diagnosis of C. bantiana infection. Given the extent of her disease, complete surgical resection was not feasible. She required multiple surgical debridement procedures and prolonged antifungal therapy, including the instillation of intraventricular amphotericin B. With aggressive surgical and medical management, despite her continued neurologic deficits, she remains alive 3 years after her initial diagnosis. To our knowledge, this is one of a few published pediatric cases of CNS phaeohyphomycosis and the first with the causative pathogen identified by plasma mNGS. CONCLUSION: CNS phaeohyphomycosis is a serious, life-threatening infection. The preferred management includes a combination of surgical resection and antifungal therapy. In cases complicated by refractory ventriculitis, intraventricular antifungal therapy can be considered as adjuvant therapy. Direct sampling of the CNS for pathogen identification and susceptibility testing is the gold standard for diagnosis; however, the use of plasma mNGS may expedite the diagnosis.

Epidemiology and variability in management of acute mastoiditis in children.

BACKGROUND: To evaluate the epidemiology, management and outcome of acute mastoiditis (AM) in children and to improve strategies for antimicrobial stewardship. METHODS: We conducted a retrospective observational study of children aged >6 months to ≤18 years of age admitted to a tertiary care hospital with AM over an 8-year period (2011-2019). Electronic medical records were reviewed to collect data. RESULTS: A total of 129 patients met inclusion criteria for AM during this time period. Eighty-one (63 %) were males with 110 (81 %) White and 67 (52 %) non-Hispanic. The median age at presentation was 6.4 years (3-10.1 years). Ear protrusion was associated with reduced odds of having AM with intracranial extension (ICE) (OR 0.307, 95 % CI = 0.107-0.883) whereas presence of headaches and/or neck pain increased the odds of having AM with ICE (OR = 3.96, 95%CI 1.29-12.1). The most common etiologies were Streptococcus pyogenes (n = 23, 19.2 %), Pseudomonas aeruginosa (n = 20, 17 %), and Streptococcus pneumoniae (n = 15, 12.5 %). Empiric antibiotic selection and duration of therapy was highly variable. The most common empiric antibiotic used was intravenous vancomycin with a third generation cephalosporin (n = 45, 34.8 %). Majority completed course (n = 92; 73 %) with an oral antibiotic. Shorter (≤10 and ≤14 days) versus longer courses (>10 and >14 days) did not affect readmission rates for AM without ICE. CONCLUSION: There is high variability of treatment of AM in children. Broad spectrum antibiotics, especially vancomycin were used most frequently despite low rates of Methicillin Resistant Staphylococcus aureus. The use of antibiotic stewardship is essential for judicious antibiotic use.

Bannwarth Syndrome: A Rare Manifestation of Pediatric Lyme Neuroborreliosis.

Lymphocytic meningoradiculitis (Bannwarth syndrome) is a rare manifestation of Lyme neuroborreliosis in children. It is the most common clinical manifestation of early Lyme neuroborreliosis in adults in European countries where the disease is endemic but is rare in children. We report an imported case of Bannwarth syndrome in a pediatric patient and review the literature for other pediatric cases reported.

An evidence-based, risk-adapted algorithm for antifungal prophylaxis reduces risk for invasive mold infections in children with hematologic malignancies.

BACKGROUND: Children with hematologic malignancies, especially those who receive intensive chemotherapy, are at high risk for invasive mold infections (IMI) that confer substantial mortality. Randomized controlled trials support the use of antifungal prophylaxis with antimold activity as an optimal strategy for risk reduction in this population, but studies outlining the practical application of evidence-based recommendations are lacking. PROCEDURE: We conducted a 15-year, single-institution retrospective review in a diverse cohort of children with hematologic malignancies treated with chemotherapy to determine the incidence of proven or probable IMI diagnosed between 2006 and 2020. Multivariable logistic regression was used to identify host and disease factors associated with IMI risk. We then compared the incidence and type of IMI and related factors before and after 2016 implementation of an evidence-based, risk-adapted antifungal prophylaxis algorithm that broadened coverage to include molds in patients at highest risk for IMI. RESULTS: We identified 61 cases of proven or probable IMI in 1456 patients diagnosed with hematologic malignancies during the study period (4.2%). Implementation of an antifungal prophylaxis algorithm reduced the IMI incidence in this population from 4.8% to 2.9%. Both Hispanic ethnicity and cancer diagnosis prior to 2016 were associated with risk for IMI. CONCLUSION: An evidence-based, risk-adapted approach to antifungal prophylaxis for children with hematologic malignancies is an effective strategy to reduce incidence of IMI.

Rat Bite Fever: Variability in Clinical Presentation and Management in Children.

Rat bite fever is a systemic illness most commonly caused by Streptobacillus moniliformis that is classically characterized by fever, rash and migratory polyarthritis. Here, we highlight the highly variable clinical presentations of rat bite fever in children and the importance of maintaining a high degree of suspicion so appropriate treatment can be promptly initiated.

Effectiveness of Modalities to Teach Evidence Based Medicine to Pediatric Clerkship Students: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of a traditional didactic session (TDS) as compared to a self-paced, interactive, multimedia module (SPM) on the application of evidence-based medicine (EBM) skills among medical students during their inpatient pediatric rotation. METHODS: We conducted a randomized controlled trial from June, 2017 to June, 2018 at a quaternary care children's hospital. Students were randomized to TDS or SPM during each 2-week block. All students completed a critical appraisal tool (CAT) of evidence related to a clinical question in a standardized appraisal form and self-reflected about the EBM process. The primary outcome was the numeric score of the CAT derived by using the validated Fresno tool. Secondary outcomes of knowledge, attitudes, confidence, and self-reported behaviors related to EBM were measured using validated surveys. Statistical analysis was performed using Student's t test for CAT scores and mixed-model procedure (PROC MIXED), with subject as random effect and time as repeated measure for the secondary outcomes. RESULTS: One hundred twenty-seven clerkship students were included. Overall, there was no significant difference in mean CAT scores for TDS (n = 59) versus SPM (n = 66) groups (90.3 vs 92.0, P = .65). There were no significant differences between SPM and TDS groups for knowledge (P = .66), attitudes (P = .97), confidence (P  = .55), and accessing evidence (P = .27). Both groups showed significant gains in knowledge, attitudes, confidence, and accessing evidence from baseline to postcourse. Improvements in knowledge and confidence were sustained at 3-months. CONCLUSION: A SPM learning module is as effective as a TDS module for application of EBM concepts and knowledge to patient care.

Evaluation of Antimicrobial Utilization in the Pediatric Drowning Population.

BACKGROUND: Management of pediatric drowning often includes evaluation and treatment of infectious disease. There are few data describing the infections associated with pediatric drowning. METHODS: A descriptive retrospective study was designed, and patients aged < 19 years admitted for > 24 hours to our institution after a drowning were included from January 2011 through June 30, 2017. Data collection included patient demographics, submersion injury details, resuscitation details, patient admission details, chest radiograph on admission, use of intubation and mechanical ventilation, hospital length of stay, culture data, antimicrobial use, and mortality. Descriptive statistical methods (mean and standard deviation, median and range, percentage) were used to characterize the patient population, and Fisher exact test was used to evaluate the association between antimicrobial use in the first 72 hours of admission and mortality. RESULTS: A total of 114 patients met study criteria (male, 59.7%; median age, 3.7 years [range, 0.15-17.79 years]). Median hospital length of stay was 2 days (range, 1-60 days). Intensive care unit admission occurred in 80.7%, intubation occurred in 46.5%, and mortality was 18.4%. The most common submersion location was a pool (76.3% [n = 87]) with water primarily characterized as freshwater (82.5% [n = 94]). Reported submersion time for the majority of patients was < 5 minutes (54.4%) with cardiopulmonary resuscitation in 78.1%. In the first 72 hours after admission, culture were obtained in 40 patients (35.1%), and 27.5% of these cultures were positive. The primary organisms identified were consistent oropharyngeal flora. Antimicrobials were initiated in 50% of the patient population with clindamycin as most common. There was not a significant association between antimicrobial use in the first 72 hours after admission and mortality (17.2% vs 19.6%, P = .81). CONCLUSIONS: Infectious disease associated with pediatric drowning in pools is uncommon. Empiric use of antimicrobials does not appear to affect outcomes.

Hand Cellulitis and Abscess From a Kinkajou Bite: a Case Report and Review of Kinkajou Bites in Humans.

Medical literature on the microbiology of kinkajou bites is scarce. We present a patient presenting with hand cellulitis and abscess after a kinkajou bite that grew Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum. We review the literature regarding microbiology and management of kinkajou bites.

IV Antibiotic Durations for Nontyphoidal Salmonella Bacteremia.

OBJECTIVES: The objective was to determine if shorter intravenous (IV) antibiotic (<7 days) for nontyphoidal Salmonella bacteremia (NTS-B) is noninferior to longer (≥7 days) in terms of 30-day emergency department (ER) or rehospitalization in healthy children. METHODS: A retrospective observational study of otherwise healthy children admitted to a children's hospital in the United States from 2006 to 2017 with NTS-B was conducted. RESULTS: Of 231 patients reviewed, 51 patients had NTS-B. Median IV duration for all patients was 5 days (range 2-17 days). The short-duration group (SDG) (<7 days; N = 32) had a median of 4 days (range 2-6 days) of IV antibiotics versus a median of 9 days (range 7-17 days) in the long-duration group (LDG) (≥7 days; N = 19). The hospital length of stay in the SDG was 3.5 days versus 7 days in the LDG (P < .001). The SDG was significantly noninferior to the LDG in terms of ER visits or hospital readmissions within 30 days (absolute risk difference 5.3%; 95% confidence interval -16% to -5%), with only 1 child in the LDG returning to the ER. CONCLUSIONS: IV antibiotic durations for NTS-B in otherwise healthy children were variable within our study group. Shorter courses (<7 days) of IV antibiotics were noninferior to longer courses in healthy children and reduced hospital stay. ER visits and readmissions were rare, and there was no association between IV treatment duration and risk of relapse. Prospective studies are needed to study the safety of shorter courses, but given the absence of evidence favoring longer courses, shorter courses can be considered.

Population Pharmacokinetic Assessment of Vancomycin Dosing in the Large Pediatric Patient.

The most appropriate vancomycin dosing strategy in pediatric patients weighing ≥70 kg (weight based versus non-weight based) to achieve an area under the concentration-time curve (AUC) of ≥400 mg·liter/h and a trough concentration of <20 mg/liter is not known. Population pharmacokinetic analysis determined that dosing of vancomycin should be weight based using fat-free mass, with appropriate adjustment for kidney dysfunction.

Vancomycin associated acute kidney injury in pediatric patients.

INTRODUCTION: Vancomycin associated acute kidney injury (vAKI) is a well known complication in pediatric patients. Identification and characterization of the incidence and risk factors for vAKI in the pediatric population would assist clinicians in potentially preventing or mitigating vAKI. METHODS AND MATERIALS: A 6 year retrospective cohort study was designed. Patients were included if they were < 19 years of age, received vancomycin as inpatients, and had a baseline SCr and one other SCr drawn during and up to 72 hours after the discontinuation of vancomycin. Data collection included patient demographics, vancomycin doses and length of therapy, vancomycin serum concentrations, and concomitant medications. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to characterize acute kidney injury. Descriptive statistical methods were used and ordinal logistic regression was employed to determine variables significantly associated with vAKI. RESULTS: A total of 7,095 patients met study criteria (55.4% male, median age 4.1 years (IQR 0.67-11.2 years)). Mechanical ventilation was used in 7.9% (n = 563) and mortality was 4.9% (n = 344). A total of 153 concomitant medications were identified. A median of 5 (IQR 3-7) SCr values were obtained and median SCr prior to vancomycin was 0.39 (IQR 0.28-0.57) mg/dL (CrCl 134±58 mL/min/1.73m2). Vancomycin was administered for a median of 2 (IQR 1-3) days (14.9±1.6 mg/kg/dose). vAKI was present in 12.2% (n = 862: KDIGO stage 1 (8.30%, n = 589), KDIGO stage 2 (1.94%, n = 138) KDIGO stage 3 (1.89%, n = 134)). Mean vancomycin serum concentration at 6-8 hours after a dose for patients with vAKI (10.7±8.9 mg/L) was significantly, but not clinically different for patients with no vAKI (7.5±6.3 mg/L). (p<0.05) Ordinal logistic regression identified total dose of vancomycin, vancomycin administration in the intensive care unit, and concomitant medication administration as significant for vAKI. In particular, concomitant administration of several different medications, including nafcillin, clindamycin, and acetazolamide, were noted for strong associations with vAKI. (p<0.05). CONCLUSIONS: Moderate to severe acute kidney injury due to vancomycin is infrequent in children and associated with concomitant medication use and total dose of vancomycin. Serum vancomycin concentrations are not useful predictors of vAKI in the pediatric population.

Neonatal Bacteremia and Cutaneous Lesions Caused by Photorhabdus luminescens: A Rare Gram-Negative Bioluminescent Bacterium.

Photorhabdus luminescens is a rare bacterium that causes human disease. In this report, we describe the case of a neonate with Photorhabdus luminescens bacteremia, including clinical presentation and treatment; we also report a literature review of rare human diseases.

Cost-effectiveness and Improved Parent and Provider Satisfaction With Outpatient Management of Pediatric Oncology Patients, With Low-risk Fever and Neutropenia.

On the basis of significant evidence for safety, the international pediatric fever and neutropenia committee recommends the identification and management of patients with "low-risk fever and neutropenia" (LRFN), outpatient with oral antibiotics, instead of traditional inpatient management. The aim of our study was to compare the cost-per-patient with these 2 strategies, and to evaluate parent and provider satisfaction with the outpatient management of LRFN. Between March 2016 and February 2017, 17 LRFN patients (median absolute neutrophil count, 90/µL) were managed at a single institution, per new guidelines. Fifteen patients were discharged on presentation or at 24 to 48 hours postadmission on oral levofloxacin, and 2 were inadvertently admitted off protocol. The mean cost of management for the postimplementation cohort was compared with a historic preimplementation control group. Satisfaction surveys were completed by parents and health care providers of LRFN patients. The mean total cost of an LRFN episode was $12,500 per patient preimplementation and $6168 postimplementation, a decrease of $6332 (51%) per patient. All parents surveyed found outpatient follow-up easy; most (12/14) parents and all (16/16) providers preferred outpatient management. Outpatient management of LRFN patients was less costly, and was preferred by a majority of parents and all health care providers, compared with traditional inpatient management.

Pediatric invasive fungal rhinosinusitis: An investigation of 17 patients.

PURPOSE: To investigate outcomes of pediatric patients at a single institution with invasive fungal rhinosinusitis (IFRS) and to determine variables that impact overall survival. METHODS: All pediatric patients at a large tertiary children's hospital diagnosed with IFRS confirmed by surgical pathology from 2009 to 2015 were retrospectively reviewed. Demographics, underlying diseases, symptoms, antifungal therapy, absolute neutrophil count (ANC), surgical management,and outcomes were analyzed. RESULTS: Seventeen patients were identified with IFRS with an average age of 8.7 years and 53% male. Hematologic malignancy was the most common (n = 13) underlying disease. The most common presenting symptoms were fever (82%) and congestion (41%). 15 patients had severe neutropenia (Absolute Neutrophil Count (ANC) < 500) within 2 weeks prior to diagnosis. The average ANC at time of diagnosis was 1420 cells/uL. 16 patients were treated with serial nasal endoscopy and debridement, while 1 patient was treated with an open approach. 16 received combination antifungals while 1 was treated with amphotericin monotherapy. The most common genus cultured was Fusarium (n = 6). The average number of surgical interventions was 3.4, with the average interval between interventions 6.2 days. 13 of 17 (76%) were cleared of IFRS. Overall survival at 6 months was 41%. CONCLUSION: Pediatric IFRS is a life-threatening disease that requires a coordinated surgical and medical approach. Despite a relatively high local control rate, overall mortality remains disappointingly high, reflecting the disease's underlying pathogenesis - lack of host defense and risk of disseminated fungal infection. Further investigation is necessary to reveal optimal management with regards to antifungal therapy, surgery, and utility of labs.

Failure to Validate a Multivariable Clinical Prediction Model to Identify Pediatric Intensive Care Unit Patients at High Risk for Candidemia.

We attempted to validate a previously derived clinical prediction rule for candidemia in the pediatric intensive care unit. This multicenter case control study did not identify significant association of candidemia with most of the previously identified predictors. Additional study in larger cohorts with other predictor variables is needed.

Risk factors of amphotericin B toxicty in the nonneonatal pediatric population.

BACKGROUND: Amphotericin B (AmB) traditionally has been the mainstay of therapy for children with candidemia but is associated with drug-related toxicities (DRT). Studies investigating the risk factors for AmB DRT in children are limited. METHODS: A retrospective review of patients aged 6 months to ≤18 years with candidemia who received ≥1 dose of AmB from 2003 to 2009 was conducted at Texas Children's Hospital, Houston, TX. Patient demographics, risk factors, drug dosages, laboratory adverse effects and infusion-related side effects (INFRT) were recorded. RESULTS: A total of 223 episodes of candidemia occurred in 179 patients. AmB was administered in 172 (77%) episodes. Amphotericin B deoxycholate, Amphotericin B lipid complex and liposomal Amphotericin B were administered in 65 (38%), 96 (55%) and 11 (6.4%) episodes, respectively. When the first episode of AmB use was analyzed separately (n = 138), DRT occurred in 83% (n = 114); nephrotoxicity occurred in 45% (n = 62), hypokalemia in 47% (n = 62) and INFRT in 31 % (n = 41). The most common INFRT was chills and rigors (80%, n = 33) followed by fever (31.7%, n = 13) and hypotension (9.7%, n = 4). Patients with lower baseline creatinine clearance were at increased risk of having nephrotoxicity than those with higher baseline creatinine clearance (P = 0.004). Nephrotoxicity was less likely in patients who received immunosuppressants (P = 0.02). Neutropenia (P = 0.02) and prior hypokalemia (P = 0.001) were independently associated with hypokalemia. The receipt of premedication was independently associated with a lower likelihood of INFRT (P ≤ 0.0001). It is important to note that most AmB-related DRT was quickly reversible. CONCLUSIONS: AmB-associated DRT was common and reversible in our nonneonatal pediatric population. Prospective studies are required to further evaluate risk factors and determine whether they are modifiable.

Candida non-albicans versus Candida albicans fungemia in the non-neonatal pediatric population.

BACKGROUND: Non-albicans Candida (NAC) species have been implicated as major pathogens in patients with hospital-acquired candidemia. Few studies have investigated the impact of NAC fungemia among pediatric patients outside of the neonatal age group. MATERIALS/METHODS: Between 2000 and 2009, we performed a retrospective case-control study in children aged 6 months to ≤18 years with blood culture proven candidemia at Texas Children's Hospital, Houston, TX. RESULTS: A total of 276 episodes of candidemia occurred in 226 patients. The overall incidence ranged between 0.06 and 0.3 per 1000 inpatient days. The median patient age was 50 months (range, 6 months to ≤18 years) with 55.4% males; 40.2% Hispanics; and 31.8% whites. Candida albicans (CA) was the most common (44.2%) species although, collectively, NAC was more frequently (55.8%) isolated. Among the NAC group, Candida parapsilosis was most common (23.9%) followed by Candida tropicalis (14.8%), Candida glabrata (6.5%), and Candida lusitaniae (5.4%). No difference was found between CA and NAC candidemia in terms of demographics, underlying diagnosis, risk factors, clinical features, dissemination, or 30-day mortality. Disseminated candidiasis was independently associated with the use of vasopressors (adjusted odds ratio [OR], 4.58; confidence interval [CI]: 1.03-20.5; P = 0.05), prolonged fungemia (≥3 days of persistently positive cultures) after catheter removal (OR, 3.2; CI: 1.08-9.3; P = 0.04), and neutropenia (OR, 4.06; CI: 1.2-13.2; P = 0.02), but not with NAC fungemia. CONCLUSIONS: Though CA was the single most common species, NAC species collectively have emerged as the predominant pathogens responsible for candidemia in non-neonatal patients at our institution. Risk factors, clinical features, and outcomes were not different between the 2 groups.