Population pharmacokinetics of fluconazole in young infants.

Fluconazole is being increasingly used to prevent and treat invasive candidiasis in neonates, yet dosing is largely empirical due to the lack of adequate pharmacokinetic (PK) data. We performed a multicenter population PK study of fluconazole in 23- to 40-week-gestation infants less than 120 days of age. We developed a population PK model using nonlinear mixed effect modeling (NONMEM) with the NONMEM algorithm. Covariate effects were predefined and evaluated based on estimation precision and clinical significance. We studied fluconazole PK in 55 infants who at enrollment had a median (range) weight of 1.02 (0.440 to 7.125) kg, a gestational age at birth (BGA) of 26 (23 to 40) weeks, and a postnatal age (PNA) of 2.3 (0.14 to 12.6) weeks. The final data set contained 357 samples; 217/357 (61%) were collected prospectively at prespecified time intervals, and 140/357 (39%) were scavenged from discarded clinical specimens. Fluconazole population PK was best described by a one-compartment model with covariates normalized to median values. The population mean clearance (CL) can be derived for this population by the equation CL (liter/h) equals 0.015 . (weight/1)(0.75) . (BGA/26)(1.739) . (PNA/2)(0.237) . serum creatinine (SCRT)(-4.896) (when SCRT is >1.0 mg/dl), and using a volume of distribution (V) (liter) of 1.024 . (weight/1). The relative standard error around the fixed effects point estimates ranged from 3 to 24%. CL doubles between birth and 28 days of age from 0.008 to 0.016 and from 0.010 to 0.022 liter/kg/h for typical 24- and 32-week-gestation infants, respectively. This population PK model of fluconazole discriminated the impact of BGA, PNA, and creatinine on drug CL. Our data suggest that dosing in young infants will require adjustment for BGA and PNA to achieve targeted systemic drug exposures.

Management of odontogenic orbital cellulitis.

This work describes a series of patients with odontogenic orbital cellulitis (OOC), focusing on rate of abscess formation, need for surgical intervention, and imaging findings helpful for rapid diagnosis. Review of a current case and 22 patients with OOC from the scientific literature demonstrated periapical lucency as the most commonly (36.4%) reported finding on facial and orbital computerized tomography (CT) scan. Orbital abscess occurred in 72.7% of cases, and tooth extraction and/or abscess drainage was required in 95.5% of cases reviewed for control of infection. The current case presented with periapical lucency on CT scan, developed orbital abscess despite broad spectrum antibiotic therapy, and required multiple surgical interventions for disease resolution. Though our patient regained excellent vision, OOC often can result in severe vision loss. Periapical lucency on CT can help identify this atypical origin of cellulitis that is strongly associated with abscess formation and need for surgical intervention.

Controlling external factors affecting accounts receivable.

External factors such as complex billing arrangements, decreasing healthcare benefits, and increasing numbers of uninsured workers contribute to a hospital's outstanding accounts receivable. Instituting measures for getting payment in full and as soon as possible can help control for outside influences and reduce outstanding receivables.

Rapid separation and quantitation of mixed microorganisms by filtration and bioluminescence.

A membrane filtration/bioluminescence system was developed for the differentiation and quantitation of mixed populations of microorganisms. Samples containing microorganisms were filtered through two membrane filters of descending pore size. The microorganisms retained on the filter contain ATP that can be extracted and measured on the filter via the firefly luciferase-luciferin bioluminescence assay. Results, obtained in less than 20 min, show a good correlation (r greater than or equal to 0.95) between the light produced and the number of organisms in the sample. Using these techniques, Escherichia coli can be separated from yeast or mold and measured in samples containing both microorganisms. When lysostaphin is used to selectively lyse Staphylococci on the filter, the specific quantification of these bacteria among other microorganisms can also be accomplished. The filtration/bioluminescence technique offers the potential of being a rapid and sensitive method to differentiate and detect microorganisms, by selective sizing or lysing, in a variety of samples.