Early diagnosis with sequencing and successful treatment of Bipolaris prosthetic valve endocarditis.

We present a case of a 48-year-old man with congenital bicuspid aortic valve, history of Ross procedure, prosthetic pulmonary valve and homograft with rapid molecular diagnosis and prompt surgical and medical treatment for Bipolaris fungal endocarditis with excellent outcome with early valve replacement, debridement, combination antifungal therapy, ongoing suppressive therapy after treatment.

Identification of an Emergent Pathogen, Bartonella vinsonii, Using Next-Generation Sequencing in a Patient With Culture-Negative Endocarditis.

Diagnosis and treatment of culture negative endocarditis remains a challenge. This report describes a rare cause of endocarditis in humans, Bartonella vinsonii, identified through next generation sequencing of plasma microbial cell-free DNA with confirmation of cardiac valve tissue infection through immunohistochemical staining and polymerase chain reaction.

Acute Flaccid Myelitis Among Hospitalized Children in Texas, 2016.

BACKGROUND: Acute flaccid myelitis is characterized by acute-onset flaccid limb weakness with predominantly gray matter lesions in the spinal cord spanning one or more segments. Rates of full recovery are poor, and there is no standard treatment or definitive cause. METHODS: This is a retrospective review of children diagnosed with acute flaccid myelitis in Texas during 2016. Patients were identified through a Texas collaborative of six hospitals in four major metropolitan areas. Data abstraction included health history, illness presentation, medical treatments, laboratory studies, imaging data, recovery, and ability to perform activities of daily living up to approximately two years from illness onset. RESULTS: Among all sites, 21 patients met inclusion criteria. Treatments varied with the most common being intravenous immunoglobulin, high-dose methylprednisolone, and plasmapheresis. No differences were seen in response to medical treatments. A potential etiology was found in 12 (57%) cases, including four with enterovirus D68. Five cases recovered fully. Of the 16 patients without full recovery, abilities ranged from (1) able to perform all activities of daily living for age independently (n = 5), (2) mild deficits (n = 5), and (3) substantial reliance on caregivers for activities of daily living (n = 6). CONCLUSION: Many reports describe symptoms and outcomes of acute flaccid myelitis, but limited data are available on long-term functional outcomes. We were unable to make a strong case for any single cause or treatment modality. Fortunately, the majority of patients (15, 71%) were able to perform activities of daily living with complete independence or only mild deficits.

Comparison of pharmacokinetics and safety of voriconazole intravenous-to-oral switch in immunocompromised adolescents and healthy adults.

The current voriconazole dosing recommendation in adolescents is based on limited efficacy and pharmacokinetic data. To confirm the appropriateness of dosing adolescents like adults, a pharmacokinetic study was conducted in 26 immunocompromised adolescents aged 12 to <17 years following intravenous (IV) voriconazole to oral switch regimens: 6 mg/kg IV every 12 h (q12h) on day 1 followed by 4 mg/kg IV q12h, then switched to 300 mg orally q12h. Area under the curve over a 12-hour dosing interval (AUC(0-12)) was calculated using a noncompartmental method and compared to the value for adults receiving the same dosing regimens. On average, the AUC(0-12) in adolescents after the first loading dose on day 1 and at steady state during IV treatment were 9.14 and 22.4 µg·h/ml, respectively (approximately 34% and 36% lower, respectively, than values for adults). At steady state during oral treatment, adolescents also had lower average exposure than adults (16.7 versus 34.0 µg·h/ml). Larger intersubject variability was observed in adolescents than in adults. There was a slight trend for some young adolescents with low body weight to have lower voriconazole exposure. It is likely that these young adolescents may metabolize voriconazole more similarly to children than to adults. Overall, with the same dosing regimens, voriconazole exposures in the majority of adolescents were comparable to those in adults. The young adolescents with low body weight during the transitioning period from childhood to adolescence (e.g., 12 to 14 years old) may need to receive higher doses to match the adult exposures. Safety of voriconazole in adolescents was consistent with the known safety profile of voriconazole.

Pharmacokinetics and pharmacodynamics of linezolid in children with cystic fibrosis.

UNLABELLED: Alternative antimicrobial regimens are needed for treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated pulmonary exacerbations in children with cystic fibrosis (CF). There are no published pharmacokinetic (PK) and pharmacodynamic (PD) data for linezolid in children with CF. OBJECTIVES: (1) To determine the PK and PD profile of linezolid among children with CF; (2) to characterize the effect of linezolid on MRSA infection; (3) to determine the effect of age and CF transmembrane regulator (CFTR) gene mutations on drug clearance. HYPOTHESES: Linezolid clearance is enhanced in children with CF requiring a higher dosage regimen. Age and CFTR gene mutations affect drug clearance. METHODS: This was a retrospective cohort study; medical records of children with MRSA-associated pulmonary exacerbations treated with linezolid (10 mg/kg/dose IV every 8h) were reviewed. Linezolid peak and trough concentrations in serum were determined by high performance liquid chromatography, PK profiles determined using standard noncompartmental method, and PD indices were evaluated. RESULTS: 10 children (mean +/- SD, 10.2 +/- 5.5 years) received 14 courses of linezolid at 10 +/- 0.4 mg/kg/dose every 8h for 15.4 +/- 3.2 days. Seven had homozygous DeltaF508 CFTR mutation. Peak and trough linezolid concentrations varied widely (range, 8.4-20.5 and 0.1-11.5 mcg/mL respectively). The PK profile of children <10 years differed significantly from older patients (>or=10 years). The PK indices of children with homozygous DeltaF508 differed marginally from those with heterozygous CFTR mutations, but there were too few subjects to allow separation of age and CFTR mutations effect. No patient achieved the target PD ratio of AUC/MIC >80. MRSA persisted in sputum or throat culture after treatment with linezolid. CONCLUSIONS: Additional PK and PD data are needed to optimize linezolid therapy in children with cystic fibrosis; it is likely that higher doses will be needed.