Fred F. Barrett

Evaluation of vancomycin use in a pediatric teaching hospital based on CDC criteria.

This study was performed to determine whether vancomycin use at our pediatric hospital was consistent with modified Centers for Disease Control and Prevention guidelines. Vancomycin use was inappropriate in 54% of patients. Inappropriate use briefly decreased by 14% after educational efforts. Further education regarding vancomycin use was deemed necessary and is continuing.

Myocardial function in rocky mountain spotted fever: Echocardiographic assessment

Nine patients with Rocky Mountain spotted fever underwent M-mode echocardiographic examination. Increased left ventricular dimension was found in 2 patients and decreased left ventricular shortening fraction in 7. Diminished mean velocity of circumferential fiber shortening, increased left ventricular systolic time intervals ratio, and increased mitral valve E point to ventricular septal separation were found in 6 patients. One patient died and at necropsy diffuse myocarditis was present. Repeat echocardiographic examination was available in the remaining 8 patients at follow-up (mean 10 months). Abnormal E mitral point to ventricular septal separation remained in 3 patients and decreased left ventricular shortening fraction in 2; in 1 there was also increased left ventricular end-diastolic dimension. Thus abnormal left ventricular function and chamber enlargement are frequently present in patients with Rocky Mountain spotted fever.

Chloramphenicol dosage and pharmacokinetics in infants and children.

Abstract: Twenty infants and children receiving intravenous chloramphenicol were studied to examine the pharmacokinetics of the parent compound and its precursor, the succinate ester (CAP‐S). Plasma samples were obtained just prior to a 30‐minute infusion of chloramphenicol succinate, immediately after or 30 minutes after infusion, and 90, 210, and 330 minutes after infusion. Complete 6‐hour urine collections were obtained during 11 studies. Plasma and urine were assayed for chloramphenicol and its succinate ester by high‐performance liquid chromatography. Peak plasma concentrations ranged from 11.0 to 51.1 μg/ml on doses of 50 to 100 mg/kg/day and were higher in the youngest age group. The elimination half‐life of chloramphenicol averaged 4.0 hours. Multilinear regression analysis demonstrated an excellent relationship between body surface area, trough plasma chloramphenicol concentration, and total body chloramphenicol clearance. The hydrolysis of succinate ester to free chloramphenicol may delay the peak free concentration, and its renal elimination (average 21 per cent of the dose administered) significantly affects chloramphenicol pharmacokinetics. The clearance of chloramphenicol exhibited enzyme saturation kinetics in one patient studied at two different doses. Dosage adjustments of intravenous chloramphenicol in children must be made in relation to the trough chloramphenicol plasma concentration, renal elimination of CAP‐S, and possible saturation of chloramphenicol metabolism.

Chloramphenicol Clearance in Infants

Abstract: Chloramphenicol clearance was evaluated over one dosing interval in 10 infants after at least 24 hours of therapy to evaluate dosage guidelines using a specific chemical assay. Serum samples were obtained prior to and at 1, 2, 4, and 6 hours after the start of a 20‐minute infusion of 25 mg/kg chloramphenicol as the sodium succinate. The chemical assay used is technically simple and is specific for unesterified chloramphenicol. Peak serum concentrations ranged from 20.9 to 94.0 μg/ml and occurred from 1 to 4 hours after infusion. Clearances ranged from 0.058 to 0.236 1./kg · hr and paralleled previously reported results using different assay methodology. The 4‐hour serum chloramphenicol concentrations were significantly lower (P < 0.05) in infants on phenobarbital. The currently recommended dose of chloramphenicol for severe infections, 100 mg/kg per day, is excessive in some infants. Widely divergent clearance rates prohibit uniform dosage guidelines so that serum level monitoring with an assay specific for chloramphenicol is essential.

Infections of Central-Nervous-System Shunts

Hydrocephalus has been recognized throughout the ages as a condition in which excess fluid accumulates within the cranium. Hippocrates is credited with the first efforts to drain the dilated ventricles.1 During the 1700–1800s, treatment of hydrocephalus was limited to bleeding, purges, and diuretics. Head wrapping, radiation therapy, and thyroid extract were also transiently believed to be efficacious. Some of the earliest surgical efforts at control of this condition involved removal of the choroid plexus, tying the common carotid arteries, and intermittent puncture of the lateral ventricles.1,2

1183 MICROBIOLOGIC AND CLINICAL CHARACTERIZATION OF COAGULASE-NBGATIVE STAPHYLOCOCCI FROM CEREBROSPINAL FLUID SHUNTS

Recent studies have suggested that bacterial adherence to smooth surfaces may be important in the pathogenesis of medical device infections with coagulase-negative staphylococci (CNS). We collected and characterized 84 strains of CNS (51 pathogens and 33 contaminants) cultured from cerebrospinal fluid (CSF) shunts of pediatric patients. Species distribution was similar for both pathogens and contaminants except that 20% of the pathogens and none of the contaminants were phospnatase-negative Staphylococcus epidermidis (p<.01). Neither species nor antibiotic susceptibility correlated with clinical outcome. All patients treated with total shunt removal were cured while only 33% of the patients treated with antibiotics alone were cured. As an index of bacterial adherence, we measured the optical density (OD) of stained bacterial films adherent to tissue culture plates. Pathogenic CNS were more adherent than CSF contaminants (mean OD .510 vs .307 p<.05). Furthermore, 5/6 (83%) of infections due to non-adherent organisms were cured with antibiotics alone compared to 17/43 (40%) of infections due to adherent organisms (p<.05). These results suggest that adherence to CSF shunts is important in the pathogenesis of CSF shunt infections.