Kawasaki Disease Outcomes and Response to Therapy in a Multiethnic Community: A 10-Year Experience.

OBJECTIVES: To describe the epidemiology, response to therapy, and outcomes of Kawasaki disease in a multiethnic community with a large Hispanic and Asian population. STUDY DESIGN: We analyzed prospectively collected data from 788 unselected patients with Kawasaki disease diagnosed and treated at a single medical center over a 10-year period. RESULTS: The average incidence of Kawasaki disease in children <5 years in San Diego County over the 10 years from 2006 to 2015 was 25 per 100 000 children, with the greatest incidence (50 per 100 000) for Asian/Pacific Islanders. Compared with other race/ethnicities, Asian/Pacific Islander patients with Kawasaki disease were younger, were diagnosed earlier in the course of their fever, had higher levels of inflammatory markers, and were more likely to develop aneurysms. There was no difference across race/ethnicity groups in response to intravenous immunoglobulin therapy. Filipino children had the highest recurrence rates (9.1%; 95% CI, 3.0%-22.6%) and 12 of 788 patients (1.5%) had a first- or second-degree relative with a history of Kawasaki disease. After correcting for age of onset, sex, and illness day at diagnosis, Asian/Pacific Islander children had an increased risk of developing aneurysms (aOR, 2.37; 95% CI, 1.37-4.11; P = .002). Overall, 180 of 788 patients (22.8%) had a maximal Z score of 2.5-10.0 and 14 of the 788 patients (1.8%) had a maximal Z score ≥10.0 despite 84% of these patients being treated within 10 days of fever onset. CONCLUSIONS: Our data provide new insights into the natural history of treated Kawasaki disease in a multiethnic population. Patient race/ethnicity influenced susceptibility to Kawasaki disease, timing of diagnosis, coronary artery outcome, and recurrence rates.

Use of Simulation Strategies to Predict Subtherapeutic Meropenem Exposure Caused by Augmented Renal Clearance in Critically Ill Pediatric Patients With Sepsis.

OBJECTIVES: The objectives of this study were to 1) define extent and potential clinical impact of increased or decreased renal elimination of meropenem in children with sepsis, based on analysis of renal function during the first 2 days of PICU stay; and 2) estimate the risk of subtherapeutic meropenem exposure attributable to increased renal clearance. METHODS: This retrospective study evaluated patients with a diagnosis of sepsis, receiving meropenem from the PICU at Rady Children's Hospital San Diego from 2015-2017. Meropenem exposure was estimated by using FDA-approved doses (20 and 40 mg/kg/dose) on day 1 and day 2 of PICU stay, based on a population pharmacokinetic (PK) model. For this population with sepsis, we assessed time-above-minimum inhibitory concentration (T>MIC) for pathogen MICs. RESULTS: Meropenem treatment was documented in 105 episodes of sepsis with a 48% rate of pathogen detection. By day 2, increased eGFR (>120 mL/min/1.73 m2) was documented in 49% of patients, with 17% meeting criteria for augmented renal clearance ([ARC] >160 mL/min/1.73 m2) and 10%, for decreased function. Simulations documented that 80% of PICU patients with ARC did not achieve therapeutic meropenem exposure for Pseudomonas aeruginosa with a MIC of 2, using standard doses to achieve a pharmacodynamic goal of 80% T>MIC. CONCLUSIONS: Approximately 3 of every 20 children with sepsis exhibited ARC during the first 48 hours of PICU stay. Simulations documented an increased risk for subtherapeutic meropenem exposure, suggesting that higher meropenem doses may be required to achieve adequate antibiotic exposure early in the PICU course.

Evolution of Ceftaroline-Resistant Mrsa in a Child with Cystic Fibrosis Following Repeated Antibiotic Exposure.

Ceftaroline is the first ß-lactam antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA). We describe a ceftaroline-resistant MRSA strain, isolated from a girl with cystic fibrosis after 22 ceftaroline treatment courses. MRSA genome sequencing documented a Tyr446Asn alteration in penicillin binding protein 2 that appeared responsible for resistance. Noncompartmental ceftaroline pharmacokinetic evaluation in our patient documented increased clearance and volume of distribution compared with adults.